Publications by authors named "Yong-Bing Xiang"

362 Publications

Dose-Response Association between Adiposity and Liver Cancer Incidence: A Prospective Cohort Study among Non-Smoking and Non-Alcohol-Drinking Chinese Women.

Cancer Epidemiol Biomarkers Prev 2021 Jun 13;30(6):1200-1207. Epub 2021 Apr 13.

School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Based on a population with very low prevalence of smoking and alcohol drinking, we examined the associations between overall obesity and fat distribution in middle age, obesity in early adulthood, and adult weight gain with the risk of liver cancer incidence.

Methods: The associations between body mass index (BMI) at study enrollment and at age 20, waist circumference (WC), hip circumference (HC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), adult weight gain, and annual average weight gain with the risk of liver cancer were estimated using Cox regression models. Multivariable-adjusted HRs and 95% confidence intervals (CIs) were calculated.

Results: After a mean follow-up time of 17.5 years, 241 liver cancer cases were identified from 69,296 participants. The HRs for per 5-kg/m increment of BMI, per 10-cm increment of WC and HC, and per 0.1-unit increment of WHtR in middle age were 1.29 (95% CI, 1.07-1.57), 1.23 (95% CI, 1.05-1.43), 1.30 (95% CI, 1.10-1.55), and 1.37 (95% CI, 1.07-1.75), respectively. The HRs for per 5-kg increment of absolute adult weight gain and per 0.5-kg/year increment of annual average weight gain were 1.15 (95% CI, 1.06-1.25) and 1.44 (95% CI, 1.08-1.92).

Conclusions: Overall and abdominal obesity in middle age and weight gain through adulthood were positively associated with liver cancer risk among non-smoking and non-alcohol-drinking women.

Impact: Based on a cohort of non-smoking and non-alcohol-drinking women, the current study confirmed the association between obesity in middle age and increased liver cancer risk and suggested weight gain through adulthood as a risk factor for liver cancer.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-1610DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172464PMC
June 2021

Population attributable risk of excess weight, abdominal obesity and physical inactivity for type 2 diabetes in Chinese men and women.

Ann Transl Med 2021 Feb;9(4):326

State Key Laboratory of Oncogene and Related Genes & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Given the high prevalence of type 2 diabetes mellitus (T2DM) in the Chinese population, it is necessary to estimate the T2DM incident attributable to obesity and physical inactivity.

Methods: We analyzed the data from the Shanghai Men's and Women's Health Studies, including 56,691 men and 70,849 women aged 40-74. The hazard ratios (HRs) and the population attributable risks (PARs) were calculated by Cox regression model and model-based estimation.

Results: A total of 3,315 male and 5,925 female cases were identified during 519,157 and 981,504 person-years, up to 31 December 2017. Excess weight, abdominal obesity were associated with the increased risks of T2DM both in women and men, while physical inactivity was only associated with an increased risk in men. A large proportion of T2DM incident cases can be attributed to excess body weight (women: 48.6%; men: 41.5%) and abdominal obesity (women: 50.4%; men: 30.3%). Physical activity was negatively associated with the risk of T2DM (P<0.01). The PARs adjusted for confounders were 3.6% for physical inactivity in men and 1.7% in women.

Conclusions: Excess weight and abdominal obesity accounted for a large proportion of T2DM incident cases in men and women; a small part of T2DM cases were attributed to physical inactivity in men. Weight control is of great significance in curbing the epidemic of diabetes.
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http://dx.doi.org/10.21037/atm-20-6121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944258PMC
February 2021

Gender differences of relationship between serum lipid indices and type 2 diabetes mellitus: a cross-sectional survey in Chinese elderly adults.

Ann Transl Med 2021 Jan;9(2):115

School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: To investigate the gender differences of the relationships between clinical serum lipid indices and type 2 diabetes mellitus (T2DM) in Chinese elderly adults.

Methods: Between 2014 and 2016, participants selected from three communities in an urban district of Shanghai were measured for serum lipid indices of low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), total cholesterol (TC), and triglyceride (TG). Age and multivariate adjusted logistic regression models were utilized to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) of serum lipid indices on T2DM prevalence.

Results: In total, 4,023 male and 3,862 female participants were included in this study, with the T2DM prevalence proportions of 13.03% and 11.73%, respectively. In association analysis, the serum levels of LDL-c, HDL-c, TC were significant between non-T2DM individuals and T2DM patients in men, but the HDL-c and TG in women. LDL-c/HDL-c, TG/HDL-c, and TC/HDL-c ratios were associated with the T2DM prevalence only in women. In the multivariate analysis, a higher serum LDL-c level was positively associated with a reduced risk of T2DM prevalence in men with OR (95% CI) of 0.57 (0.39-0.85) (P=0.006). Higher ratios of LDL-c/HDL-c, TG/HDL-c, and TC/HDL-c were all more likely associated with the decreased risks of T2DM prevalence with the ORs ranging from 0.45 to 0.62 in men (all P<0.05), but not in women.

Conclusions: High LDL-c concentration was significantly associated with a lower T2DM prevalence in men. A gender difference of the associations between the lipid ratios and T2DM prevalence was observed for LDL-c/HDL-c and TC/HDL-c ratios, which might be validated in female T2DM prevalence in the future.
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http://dx.doi.org/10.21037/atm-20-2478DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867915PMC
January 2021

Dietary fat intake and liver cancer incidence: A population-based cohort study in Chinese men.

Int J Cancer 2021 Jun 3;148(12):2982-2996. Epub 2021 Mar 3.

State Key Laboratory of Oncogene and Related Genes & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.

To date, limited studies have focused on the association between dietary fat and liver cancer risk, especially in China. Our study aims to evaluate the association between dietary fat intake and liver cancer incidence risk in men. Dietary fat intake was obtained through a validated food frequency questionnaire in a Chinese prospective cohort. The Cox regression model was utilized to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). After exclusion, 59 998 recruitments were finally analyzed with a total follow-up time of 714 339 person-years, 431 incident liver cancer cases were newly identified among them. The adjusted HRs (95% CIs) for the highest vs lowest quartile of total fat, saturated fat, monounsaturated fat (MUFA), and polyunsaturated fat (PUFA) were 1.33 (1.01-1.75), 1.50 (1.13-1.97), 1.26 (0.96-1.65), and 1.41 (1.07-1.86), and the corresponding P-trend values were .008, .005, .034, and .005, respectively. In the secondary analysis among participants tested for hepatitis B virus, we found that higher intakes of saturated fat and PUFA were also associated with increased liver cancer risks. Besides, high risks of per standard deviation alterations of the total fat, saturated fat and MUFA were detected in liver cancer, and these results were similar to those concluded from the full-cohort analysis. In conclusion, dietary intakes of total fat, saturated fat, PUFA, and probably MUFA might increase liver cancer risks. Our study provides suggestive advice to public administration on dietary suggestions, and related measures taken from managing dietary fat intake might reduce liver cancer incidence.
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http://dx.doi.org/10.1002/ijc.33507DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175242PMC
June 2021

Sub-multiplicative interaction between polygenic risk score and household coal use in relation to lung adenocarcinoma among never-smoking women in Asia.

Environ Int 2021 02 29;147:105975. Epub 2020 Dec 29.

Department of Internal Medicine, Kaohsiung Medical University Hospital, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.

We previously identified 10 lung adenocarcinoma susceptibility loci in a genome-wide association study (GWAS) conducted in the Female Lung Cancer Consortium in Asia (FLCCA), the largest genomic study of lung cancer among never-smoking women to date. Furthermore, household coal use for cooking and heating has been linked to lung cancer in Asia, especially in Xuanwei, China. We investigated the potential interaction between genetic susceptibility and coal use in FLCCA. We analyzed GWAS-data from Taiwan, Shanghai, and Shenyang (1472 cases; 1497 controls), as well as a separate study conducted in Xuanwei (152 cases; 522 controls) for additional analyses. We summarized genetic susceptibility using a polygenic risk score (PRS), which was the weighted sum of the risk-alleles from the 10 previously identified loci. We estimated associations between a PRS, coal use (ever/never), and lung adenocarcinoma with multivariable logistic regression models, and evaluated potential gene-environment interactions using likelihood ratio tests. There was a strong association between continuous PRS and lung adenocarcinoma among never coal users (Odds Ratio (OR) = 1.69 (95% Confidence Interval (CI) = 1.53, 1.87), p=1 × 10). This effect was attenuated among ever coal users (OR = 1.24 (95% CI: 1.03, 1.50), p = 0.02, p-interaction = 6 × 10). We observed similar attenuation among coal users from Xuanwei. Our study provides evidence that genetic susceptibility to lung adenocarcinoma among never-smoking Asian women is weaker among coal users. These results suggest that lung cancer pathogenesis may differ, at least partially, depending on exposure to coal combustion products. Notably, these novel findings are among the few instances of sub-multiplicative gene-environment interactions in the cancer literature.
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http://dx.doi.org/10.1016/j.envint.2020.105975DOI Listing
February 2021

Associations of coffee and tea consumption with lung cancer risk.

Int J Cancer 2020 Dec 16. Epub 2020 Dec 16.

Department of Food and Nutrition, College of Human Ecology, Seoul National University, Seoul, South Korea.

Associations of coffee and tea consumption with lung cancer risk have been inconsistent, and most lung cancer cases investigated were smokers. Included in this study were over 1.1 million participants from 17 prospective cohorts. Cox regression analyses were conducted to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Potential effect modifications by sex, smoking, race, cancer subtype and coffee type were assessed. After a median 8.6 years of follow-up, 20 280 incident lung cancer cases were identified. Compared with noncoffee and nontea consumption, HRs (95% CIs) associated with exclusive coffee drinkers (≥2 cups/d) among current, former and never smokers were 1.30 (1.15-1.47), 1.49 (1.27-1.74) and 1.35 (1.15-1.58), respectively. Corresponding HRs for exclusive tea drinkers (≥2 cups/d) were 1.16 (1.02-1.32), 1.10 (0.92-1.32) and 1.37 (1.17-1.61). In general, the coffee and tea associations did not differ significantly by sex, race or histologic subtype. Our findings suggest that higher consumption of coffee or tea is associated with increased lung cancer risk. However, these findings should not be assumed to be causal because of the likelihood of residual confounding by smoking, including passive smoking, and change of coffee and tea consumption after study enrolment.
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http://dx.doi.org/10.1002/ijc.33445DOI Listing
December 2020

Tea Drinking and Risk of Cancer Incidence: A Meta-Analysis of Prospective Cohort Studies and Evidence Evaluation.

Adv Nutr 2021 03;12(2):402-412

State Key Laboratory of Oncogene and Related Genes and Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Here we provide a comprehensive meta-analysis to summarize and appraise the quality of the current evidence on the associations of tea drinking in relation to cancer risk. PubMed, Embase, and the Cochrane Database of Systematic Reviews were searched up to June 2020. We reanalyzed the individual prospective studies focused on associations between tea drinking and cancer risk in humans. We conducted a meta-analysis of prospective studies and provided the highest- versus lowest-category analyses, dose-response analyses, and test of nonlinearity of each association by modeling restricted cubic spline regression for each type of tea. We graded the evidence based on the summary effect size, its 95% confidence interval, 95% prediction interval, the extent of heterogeneity, evidence of small-study effects, and excess significance bias. We identified 113 individual studies investigating the associations between tea drinking and 26 cancer sites including 153,598 cancer cases. We assessed 12 associations for the intake of black tea with cancer risk and 26 associations each for the intake of green tea and total tea with cancer risk. Except for an association between lymphoid neoplasms with green tea, we did not find consistent associations for the highest versus lowest categories and dose-response analyses for any cancer. When grading current evidence for each association (number of studies ≥2), weak evidence was detected for lymphoid neoplasm (green tea), glioma (total tea, per 1 cup), bladder cancer (total tea, per 1 cup), and gastric and esophageal cancer (tea, per 1 cup). This review of prospective studies provides little evidence to support the hypothesis that tea drinking is associated with cancer risk. More well-designed studies are still needed to identify associations between tea intake and rare cancers.
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http://dx.doi.org/10.1093/advances/nmaa117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009746PMC
March 2021

Mendelian randomization analyses suggest a role for cholesterol in the development of endometrial cancer.

Int J Cancer 2021 01 7;148(2):307-319. Epub 2020 Aug 7.

Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, Georgia, USA.

Blood lipids have been associated with the development of a range of cancers, including breast, lung and colorectal cancer. For endometrial cancer, observational studies have reported inconsistent associations between blood lipids and cancer risk. To reduce biases from unmeasured confounding, we performed a bidirectional, two-sample Mendelian randomization analysis to investigate the relationship between levels of three blood lipids (low-density lipoprotein [LDL] and high-density lipoprotein [HDL] cholesterol, and triglycerides) and endometrial cancer risk. Genetic variants associated with each of these blood lipid levels (P < 5 × 10 ) were identified as instrumental variables, and assessed using genome-wide association study data from the Endometrial Cancer Association Consortium (12 906 cases and 108 979 controls) and the Global Lipids Genetic Consortium (n = 188 578). Mendelian randomization analyses found genetically raised LDL cholesterol levels to be associated with lower risks of endometrial cancer of all histologies combined, and of endometrioid and non-endometrioid subtypes. Conversely, higher genetically predicted HDL cholesterol levels were associated with increased risk of non-endometrioid endometrial cancer. After accounting for the potential confounding role of obesity (as measured by genetic variants associated with body mass index), the association between genetically predicted increased LDL cholesterol levels and lower endometrial cancer risk remained significant, especially for non-endometrioid endometrial cancer. There was no evidence to support a role for triglycerides in endometrial cancer development. Our study supports a role for LDL and HDL cholesterol in the development of non-endometrioid endometrial cancer. Further studies are required to understand the mechanisms underlying these findings.
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http://dx.doi.org/10.1002/ijc.33206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7757859PMC
January 2021

Cost-Effectiveness of Drug Treatment for Chinese Patients With Stage I Hypertension According to the 2017 Hypertension Clinical Practice Guidelines.

Hypertension 2020 09 27;76(3):750-758. Epub 2020 Jul 27.

From the Department of Epidemiology and Biostatistics (Y.-F.Z., N.L., X.-Y.S., X.-F.P., A.P.), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Systolic/diastolic blood pressure of 130 to 139/80 to 89 mm Hg has been defined as stage I hypertension by the 2017 Hypertension Clinical Practice Guidelines. Drug treatment is recommended for stage I hypertensive patients aged ≥65 years without cardiovascular disease in the 2017 Hypertension Clinical Practice Guidelines but not in the 2018 Chinese guidelines. However, the cost-effectiveness of drug treatment among this subgroup of Chinese patients is unclear. This study developed a microsimulation model to compare costs and effectiveness of drug treatment and nondrug treatment for the subgroup of stage I hypertensive patients over a lifetime horizon from a government affordability perspective. Event rates of mortality and cardiovascular complications were estimated from 3 cohorts in the Chinese population. Costs and health utilities were obtained from the national statistics report and published literature. The model predicted that drug treatment generated quality-adjusted life-years of 13.52 and associated with expected costs of $6825 in comparison with 13.81 and $7328 produced by nondrug treatment over a lifetime horizon among stage I hypertensive patients aged ≥65 years without cardiovascular disease. At a willingness-to-pay threshold of $8836/quality-adjusted life-year (the GDP per capita in 2017), drug treatment only had a 1.8% probability of being cost-effective compared with nondrug treatment after 10 000 probabilistic simulations. Sensitivity analysis of treatment costs, benefits expected from treatment, health utilities, and discount rates did not change the results. Our results suggested that drug treatment was not cost-effective compared with nondrug treatment for stage I hypertensive patients aged ≥65 years without cardiovascular disease in China.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.119.14533DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7429361PMC
September 2020

Soy Intake and Colorectal Cancer Risk: Results from a Pooled Analysis of Prospective Cohort Studies Conducted in China and Japan.

J Nutr 2020 09;150(9):2442-2450

Division of Epidemiology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.

Background: Soy is commonly consumed in east Asian countries and is suggested to reduce colorectal cancer (CRC) risk. However, results from epidemiologic studies are inconsistent, despite the anti-inflammatory and antiproliferative properties of soy isoflavones and soy protein.

Objective: We evaluated the association between soy isoflavones and soy protein and CRC risk using 4 prospective cohort studies from China and Japan.

Methods: Data were pooled from the Shanghai Women's Health Study (SWHS), Shanghai Men's Health Study (SMHS), Japan Public Health Center-based Prospective Study Cohort 1 (JPHC1), and Cohort 2 (JPHC2). Cox proportional hazards models estimated HRs and corresponding 95% CIs for the association of soy protein and isoflavone intake with CRC risk. The study included 205,060 individuals, among whom 2971 were diagnosed with incident CRC over an average follow-up of 12.7 y.

Results: No statistically significant associations with CRC risk were observed for soy protein or isoflavone intake. No association was observed among ever smokers consuming higher isoflavones (HRisoflavones: 0.83; 95% CI: 0.68, 1.00) and soy protein (HRsoy protein: 0.81; 95% CI: 0.39, 1.10). However, risk reductions were observed among premenopausal women with a body mass index [BMI (kg/m2)] <23.0 at baseline for higher isoflavone (HRisoflavones: 0.58, 95% CI: 0.34, 0.98).

Conclusions: No evidence for an overall reduction in CRC risk by increasing soy food intake (i.e., protein or isoflavones) was observed. However, the association between soy and CRC risk may vary by BMI, smoking, and menopausal status among women. Future investigations are needed to further understand the biologic mechanisms observed.
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http://dx.doi.org/10.1093/jn/nxaa194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762761PMC
September 2020

Dietary fatty acids and colorectal cancer risk in men: A report from the Shanghai Men's Health Study and a meta-analysis.

Int J Cancer 2021 01 31;148(1):77-89. Epub 2020 Aug 31.

Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.

Evidence from animal models suggests that dietary fatty acids have both anticancer and tumor-promoting effects. Whether dietary fatty acids are associated with colorectal cancer (CRC) in humans remains inconclusive. We investigated associations between dietary fatty acids and risk of CRC among 59 986 men who participated in the Shanghai Men's Health Study (SMHS), an ongoing population-based prospective cohort study. We identified 876 incident CRC cases in the SMHS during a mean follow-up of 9.8 years. Associations between dietary fatty acid intake and CRC risk were evaluated by Cox proportional hazard regression analyses. Consumption of saturated fatty acids (SFA), monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) was not significantly associated with CRC risk. Multivariate hazard ratios (HRs) and respective 95% confidence intervals (CIs) for Quartile 4 vs Quartile 1 were 0.92 (0.74-1.14; P = 0.47) for SFA, 0.95 (0.79-1.16; P = 0.74) for MUFA and 1.18 (0.95-1.46; P = 0.21) for PUFA. No significant associations were found for total n-6 PUFA or total n-3 PUFA. Additionally, we performed a meta-analysis to summarize results from the present study and 28 reports from 26 additional cohorts, which supported the overall null association between dietary fatty acid intake and CRC risk among men. Docosahexanoic acid and eicosapentaenoic acid were associated with 11% to 12% reduced risk, and linoleic acid a 19% increased risk, of CRC in the meta-analysis of combined sexes. In conclusion, this population-based prospective study and meta-analysis of cohort studies found little evidence that dietary fatty acid intake was associated with risk of CRC in men.
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http://dx.doi.org/10.1002/ijc.33196DOI Listing
January 2021

Quantifying the association of low-intensity and late initiation of tobacco smoking with total and cause-specific mortality in Asia.

Tob Control 2021 05 16;30(3):328-335. Epub 2020 Jun 16.

Division of Epidemiology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.

Background: Little is known about the health harms associated with low-intensity smoking in Asians who, on average, smoke fewer cigarettes and start smoking at a later age than their Western counterparts.

Methods: In this pooled analysis of 738 013 Asians from 16 prospective cohorts, we quantified the associations of low-intensity (<5 cigarettes/day) and late initiation (≥35 years) of smoking with mortality outcomes. HRs and 95% CIs were estimated for each cohort by Cox regression. Cohort-specific HRs were pooled using random-effects meta-analysis.

Findings: During a mean follow-up of 11.3 years, 92 068 deaths were ascertained. Compared with never smokers, current smokers who consumed <5 cigarettes/day or started smoking after age 35 years had a 16%-41% increased risk of all-cause, cardiovascular disease (CVD), respiratory disease mortality and a >twofold risk of lung cancer mortality. Furthermore, current smokers who started smoking after age 35 and smoked <5 cigarettes/day had significantly elevated risks of all-cause (HRs (95% CIs)=1.14 (1.05 to 1.23)), CVD (1.27 (1.08 to 1.49)) and respiratory disease (1.54 (1.17 to 2.01)) mortality. Even smokers who smoked <5 cigarettes/day but quit smoking before the age of 45 years had a 16% elevated risk of all-cause mortality; however, the risk declined further with increasing duration of abstinence.

Conclusions: Our study showed that smokers who smoked a small number of cigarettes or started smoking later in life also experienced significantly elevated all-cause and major cause-specific mortality but benefited from cessation. There is no safe way to smoke-not smoking is always the best choice.
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http://dx.doi.org/10.1136/tobaccocontrol-2019-055412DOI Listing
May 2021

Identification of type 2 diabetes loci in 433,540 East Asian individuals.

Nature 2020 06 6;582(7811):240-245. Epub 2020 May 6.

Vanderbilt Genetics Institute, Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.

Meta-analyses of genome-wide association studies (GWAS) have identified more than 240 loci that are associated with type 2 diabetes (T2D); however, most of these loci have been identified in analyses of individuals with European ancestry. Here, to examine T2D risk in East Asian individuals, we carried out a meta-analysis of GWAS data from 77,418 individuals with T2D and 356,122 healthy control individuals. In the main analysis, we identified 301 distinct association signals at 183 loci, and across T2D association models with and without consideration of body mass index and sex, we identified 61 loci that are newly implicated in predisposition to T2D. Common variants associated with T2D in both East Asian and European populations exhibited strongly correlated effect sizes. Previously undescribed associations include signals in or near GDAP1, PTF1A, SIX3, ALDH2, a microRNA cluster, and genes that affect the differentiation of muscle and adipose cells. At another locus, expression quantitative trait loci at two overlapping T2D signals affect two genes-NKX6-3 and ANK1-in different tissues. Association studies in diverse populations identify additional loci and elucidate disease-associated genes, biology, and pathways.
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http://dx.doi.org/10.1038/s41586-020-2263-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7292783PMC
June 2020

Diet and liver cancer risk: a narrative review of epidemiological evidence.

Br J Nutr 2020 08 1;124(3):330-340. Epub 2020 Apr 1.

State Key Laboratory of Oncogene and Related Genes and Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai200032, People's Republic of China.

Primary liver cancer is the third leading cause of cancer-related death worldwide. Most patients are diagnosed at late stages with poor prognosis; thus, identification of modifiable risk factors for primary prevention of liver cancer is urgently needed. The well-established risk factors of liver cancer include chronic infection with hepatitis B virus (HBV) or hepatitis C virus (HCV), heavy alcohol consumption, metabolic diseases such as obesity and diabetes, and aflatoxin exposure. However, a large proportion of cancer cases worldwide cannot be explained by current known risk factors. Dietary factors have been suspected as important, but dietary aetiology of liver cancer remains poorly understood. In this review, we summarised and evaluated the observational studies of diet including single nutrients, food and food groups, as well as dietary patterns with the risk of developing liver cancer. Although there are large knowledge gaps between diet and liver cancer risk, current epidemiological evidence supports an important role of diet in liver cancer development. For example, exposure to aflatoxin, heavy alcohol drinking and possibly dairy product (not including yogurt) intake increase, while intake of coffee, fish and tea, light-to-moderate alcohol drinking and several healthy dietary patterns (e.g. Alternative Healthy Eating Index) may decrease liver cancer risk. Future studies with large sample size and accurate diet measurement are warranted and need to consider issues such as the possible aetiological heterogeneity between liver cancer subtypes, the influence of chronic HBV or HCV infection, the high-risk populations (e.g. cirrhosis) and a potential interplay with host gut microbiota or genetic variations.
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http://dx.doi.org/10.1017/S0007114520001208DOI Listing
August 2020

Identification of novel breast cancer susceptibility loci in meta-analyses conducted among Asian and European descendants.

Nat Commun 2020 03 5;11(1):1217. Epub 2020 Mar 5.

Departments of Health Research and Policy, School of Medicine, Stanford University, California, CA, USA.

Known risk variants explain only a small proportion of breast cancer heritability, particularly in Asian women. To search for additional genetic susceptibility loci for breast cancer, here we perform a meta-analysis of data from genome-wide association studies (GWAS) conducted in Asians (24,206 cases and 24,775 controls) and European descendants (122,977 cases and 105,974 controls). We identified 31 potential novel loci with the lead variant showing an association with breast cancer risk at P < 5 × 10. The associations for 10 of these loci were replicated in an independent sample of 16,787 cases and 16,680 controls of Asian women (P < 0.05). In addition, we replicated the associations for 78 of the 166 known risk variants at P < 0.05 in Asians. These findings improve our understanding of breast cancer genetics and etiology and extend previous findings from studies of European descendants to Asian women.
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http://dx.doi.org/10.1038/s41467-020-15046-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7057957PMC
March 2020

Long-term liver cancer incidence and mortality trends in the Changning District of Shanghai, China.

J Dig Dis 2020 Apr 31;21(4):230-236. Epub 2020 Mar 31.

School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Objective: To evaluate the trends and estimate the long-term effects of age, period and birth cohort on the incidence and mortality rates of liver cancer (LC) in an urban district of Shanghai, China.

Methods: Crude and age-standardized rates of the incidence and mortality of LC were calculated from 1973 to 2013 annually by sex, and the direction and magnitude of the trends were estimated by the average annual percentage change (AAPC) using the Joinpoint Regression Model. An age-period-cohort (APC) model was also used to evaluate the non-linear effects of calendar time and birth cohort on LC incidence and mortality.

Results: In 1973-1977 and 2008-2013 the age-standardized rates of LC incidence and mortality (per 100 000) were 24.27 and 22.60 in men, and 7.50 and 7.26 in women, respectively. Declining trends of LC incidence and mortality rates were observed for both sexes (AAPC; P < 0.05 for both). The APC models indicated that the rates of LC incidence and mortality were significantly influenced both by calendar time and birth cohort effects.

Conclusions: The incidence and mortality rates of LC have decreased in both sexes in the Changning District of Shanghai over the past four decades. Although obvious descending trends of LC incidence and mortality were detected, attention should also be paid to the LC burden for a long time in the future because of huge population size in China and the continuity of population aging.
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http://dx.doi.org/10.1111/1751-2980.12855DOI Listing
April 2020

Coffee drinking and cancer risk: an umbrella review of meta-analyses of observational studies.

BMC Cancer 2020 Feb 5;20(1):101. Epub 2020 Feb 5.

State Key Laboratory of Oncogene and Related Genes & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Background: Epidemiological studies on the association between coffee intake and cancer risk have yielded inconsistent results. To summarize and appraise the quality of the current evidence, we conducted an umbrella review of existing findings from meta-analyses of observational studies.

Methods: We searched PubMed, Embase, Web of Science and the Cochrane database to obtain systematic reviews and meta-analyses of associations between coffee intake and cancer incidence. For each association, we estimated the summary effect size using the fixed- and random-effects model, the 95% confidence interval, and the 95% prediction interval. We also assessed heterogeneity, evidence of small-study effects, and excess significance bias.

Results: Twenty-eight individual meta-analyses including 36 summary associations for 26 cancer sites were retrieved for this umbrella review. A total of 17 meta-analyses were significant at P ≤ 0.05 in the random-effects model. For the highest versus lowest categories, 4 of 26 associations had a more stringent P value (P ≤ 10). Associations for five cancers were significant in dose-response analyses. Most studies (69%) showed low heterogeneity (I ≤ 50%). Three and six associations had evidence of excessive significance bias and publication bias, respectively. Coffee intake was inversely related to the risk of liver cancer and endometrial cancer and was characterized by dose-response relationships. There were no substantial changes when we restricted analyses to meta-analysis of cohort studies.

Conclusions: There is highly suggestive evidence for an inverse association between coffee intake and risk of liver and endometrial cancer. Further research is needed to provide more robust evidence for cancer at other sites.
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http://dx.doi.org/10.1186/s12885-020-6561-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003434PMC
February 2020

Associations of choline-related nutrients with cardiometabolic and all-cause mortality: results from 3 prospective cohort studies of blacks, whites, and Chinese.

Am J Clin Nutr 2020 03;111(3):644-656

Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.

Background: Choline-related nutrients are dietary precursors of a gut microbial metabolite, trimethylamine-N-oxide, which has been linked to cardiometabolic diseases and related death. However, epidemiologic evidence on dietary choline and mortality remains limited, particularly among nonwhite populations.

Objectives: This study aimed to investigate the associations of choline-related nutrients with cardiometabolic and all-cause mortality among black and white Americans and Chinese adults.

Methods: Included were 49,858 blacks, 23,766 whites, and 134,001 Chinese, aged 40-79 y, who participated in 3 prospective cohorts and lived ≥1 y after enrollment. Cox regression models were used to estimate HRs and 95% CIs for cardiometabolic [e.g., ischemic heart disease (IHD), stroke, and diabetes] and all-cause deaths. To account for multiple testing, P values < 0.003 were considered significant.

Results: Mean choline intake among blacks, whites, and Chinese was 404.1 mg/d, 362.0 mg/d, and 296.8 mg/d, respectively. During a median follow-up of 11.7 y, 28,673 deaths were identified, including 11,141 cardiometabolic deaths. After comprehensive adjustments, including for overall diet quality and disease history, total choline intake was associated with increased cardiometabolic mortality among blacks and Chinese (HR for highest compared with lowest quintile: 1.26; 95% CI: 1.13, 1.40 and HR: 1.23; 95% CI: 1.11, 1.38, respectively; both P-trend < 0.001); among whites, the association was weaker (HR: 1.12; 95% CI: 0.95, 1.33; P-trend = 0.02). Total choline intake was also associated with diabetes and all-cause mortality in blacks (HR: 1.66; 95% CI: 1.26, 2.19 and HR: 1.20; 95% CI: 1.12, 1.29, respectively), with diabetes mortality in Chinese (HR: 2.24; 95% CI: 1.68, 2.97), and with IHD mortality in whites (HR: 1.31; 95% CI: 1.02, 1.69) (all P-trend < 0.001). The choline-mortality association was modified by alcohol consumption and appeared stronger among individuals with existing cardiometabolic disease. Betaine intake was associated with increased cardiometabolic mortality in Chinese only (HR: 1.16; 95% CI: 1.08, 1.25; P-trend < 0.001).

Conclusions: High choline intake was associated with increased cardiometabolic mortality in racially diverse populations.
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http://dx.doi.org/10.1093/ajcn/nqz318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049525PMC
March 2020

Discovery of rare coding variants in OGDHL and BRCA2 in relation to breast cancer risk in Chinese women.

Int J Cancer 2020 04 27;146(8):2175-2181. Epub 2019 Dec 27.

Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN.

The missing heritability of breast cancer could be partially attributed to rare variants (MAF < 0.5%). To identify breast cancer-associated rare coding variants, we conducted whole-exome sequencing (~50×) in genomic DNA samples obtained from 831 breast cancer cases and 839 controls of Chinese females. Using burden tests for each gene that included rare missense or predicted deleterious variants, we identified 29 genes showing promising associations with breast cancer risk. We replicated the association for two genes, OGDHL and BRCA2, at a Bonferroni-corrected p < 0.05, by genotyping an independent set of samples from 1,628 breast cancer cases and 1,943 controls. The association for OGDHL was primarily driven by three predicted deleterious variants (p.Val827Met, p.Pro839Leu, p.Phe836Ser; p < 0.01 for all). For BRCA2, we characterized a total of 27 disruptive variants, including 18 nonsense, six frameshift and three splicing variants, whereas they were only detected in cases, but none of the controls. All of these variants were either very rare (AF < 0.1%) or not detected in >4,500 East Asian women from the genome Aggregation database (gnomAD), providing additional support to our findings. Our study revealed a potential novel gene and multiple disruptive variants of BRCA2 for breast cancer risk, which may identify high-risk women in Chinese populations.
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http://dx.doi.org/10.1002/ijc.32825DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7453427PMC
April 2020

Association of Adult Weight Gain With Major Health Outcomes Among Middle-aged Chinese Persons With Low Body Weight in Early Adulthood.

JAMA Netw Open 2019 12 2;2(12):e1917371. Epub 2019 Dec 2.

Vanderbilt Epidemiology Center, Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee.

Importance: The association of weight gain from early to middle adulthood with disease risk has not been adequately studied.

Objective: To investigate the association of adult weight gain with major health outcomes in a Chinese population with low body weight in early adulthood.

Design, Setting, And Participants: This population-based cohort study assessed data from 48 377 women and 35 989 men aged 40 to 59 years at recruitment in 2 prospective cohort studies in China. The Shanghai Women's Health Study recruited 74 941 women, aged 40 to 70 years, from January 1, 1996, to December 31, 2000, and the Shanghai Men's Health Study recruited 61 482 men, aged 40 to 74 years, from January 1, 2002, to December 31, 2006. This analysis was conducted from September 1, 2017, to April 30, 2018.

Exposures: Weight gain from 20 years of age to 40 to 59 years of age.

Main Outcomes And Measures: Mortality and incidence of cancers and other chronic diseases.

Results: This analysis included 48 377 women (mean [SD] age, 47.8 [5.3] years) and 35 989 men (mean [SD] age, 49.6 [5.1] years). Per 5-kg weight gain from early to middle adulthood was associated with an approximately 10% (hazard ratio [HR], 1.09; 95% CI, 1.04-1.14 for men; HR, 1.14; 95% CI, 1.11-1.19 for women) elevated all-cause mortality and a greater than 20% (HR, 1.26; 95% CI, 1.16-1.38 for men; HR, 1.23; 95% CI, 1.14-1.33 for women) cardiovascular disease-related mortality in later life among individuals who reached a body mass index (BMI) of 23 or higher at middle adulthood. Body mass index at middle adulthood also modified the association of weight gain with risk of obesity-related cancers, with weight gain of 20 kg or more associated with increased risks both for men (HR, 1.34; 95% CI, 1.07-1.67) and for women (HR 1.45; 95% CI, 1.24-1.68). No similar associations were found for individuals with a BMI of 18.5 to 22.9. Regardless of BMI, weight gain was associated with elevated risks of type 2 diabetes, hypertension, fatty liver disease, stroke, gout, and gallstones, particularly for type 2 diabetes (HR, 7.87; 95% CI, 6.91-8.97 for women; HR, 4.95; 95% CI, 4.23-5.79 for men) and fatty liver disease (HR, 3.68; 95% CI, 3.42-3.95 for women; HR, 2.83, 95% CI, 2.56-3.13 for men) in individuals with weight gain of 20 kg or more compared with those with a healthy weight.

Conclusions And Relevance: This study found that weight gain from early to middle adulthood was associated with disease incidence and mortality in later life. The BMI at middle adulthood modified the association of weight gain with mortality and cancer incidence but not risk of other major chronic diseases.
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http://dx.doi.org/10.1001/jamanetworkopen.2019.17371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6991199PMC
December 2019

Urinary metabolites and risk of coronary heart disease: A prospective investigation among urban Chinese adults.

Nutr Metab Cardiovasc Dis 2020 03 5;30(3):467-473. Epub 2019 Nov 5.

Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA. Electronic address:

Background And Aims: Studies have linked several metabolites to the risk of coronary heart disease (CHD) among Western populations, but prospective studies among Asian populations on the metabolite-CHD association remain limited.

Methods And Results: We evaluated the association of urinary metabolites with CHD risk among Chinese adults in a nested case-control study of 275 incident cases and 275 matched controls (127 pairs of men and 148 pairs of women). Fifty metabolites were measured by a predefined metabolomics panel and adjusted using urinary creatinine. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). After adjusting for traditional CHD risk factors, urinary tryptophan showed a positive association with incident CHD: OR (95% CI) for the highest vs. lowest quartiles was 2.02 (1.15-3.56) among all study participants (p-trend = 0.02). The tryptophan-CHD association was more evident among individuals with dyslipidemia than among those without the condition (OR [95% CI] for the highest vs. lowest quartiles = 3.90 [1.86-8.19] and 0.74 [0.26-2.06], respectively; p-interaction<0.01). Other metabolites did not show significant associations with CHD risk among all study participants. However, a positive association of methionine with CHD risk was observed only among women (OR [95% CI] for the highest vs. lowest quartiles = 2.77 [1.17-6.58]; p-interaction = 0.03), and an inverse association of inosine with CHD risk was observed only among men (OR [95% CI] for the highest vs. lowest quartiles = 0.29 [0.11-0.81]; p-interaction = 0.04).

Conclusion: Elevated urinary tryptophan may be related to CHD risk among Chinese adults, especially for those with dyslipidemia.
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http://dx.doi.org/10.1016/j.numecd.2019.10.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7044070PMC
March 2020

Identification of Novel Loci and New Risk Variant in Known Loci for Colorectal Cancer Risk in East Asians.

Cancer Epidemiol Biomarkers Prev 2020 02 11;29(2):477-486. Epub 2019 Dec 11.

Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan.

Background: Risk variants identified so far for colorectal cancer explain only a small proportion of familial risk of this cancer, particularly in Asians.

Methods: We performed a genome-wide association study (GWAS) of colorectal cancer in East Asians, including 23,572 colorectal cancer cases and 48,700 controls. To identify novel risk loci, we selected 60 promising risk variants for replication using data from 58,131 colorectal cancer cases and 67,347 controls of European descent. To identify additional risk variants in known colorectal cancer loci, we performed conditional analyses in East Asians.

Results: An indel variant, rs67052019 at 1p13.3, was found to be associated with colorectal cancer risk at × 10 in Asians ( per allele deletion = 1.13, 95% confidence interval = 1.08-1.18). This association was replicated in European descendants using a variant (rs2938616) in complete linkage disequilibrium with rs67052019 ( = 7.7 × 10). Of the remaining 59 variants, 12 showed an association at < 0.05 in the European-ancestry study, including rs11108175 and rs9634162 at < 5 × 10 and two variants with an association near the genome-wide significance level (rs60911071, = 5.8 × 10; rs62558833, = 7.5 × 10) in the combined analyses of Asian- and European-ancestry data. In addition, using data from East Asians, we identified 13 new risk variants at 11 loci reported from previous GWAS.

Conclusions: In this large GWAS, we identified three novel risk loci and two highly suggestive loci for colorectal cancer risk and provided evidence for potential roles of multiple genes and pathways in the etiology of colorectal cancer. In addition, we showed that additional risk variants exist in many colorectal cancer risk loci identified previously.

Impact: Our study provides novel data to improve the understanding of the genetic basis for colorectal cancer risk.
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http://dx.doi.org/10.1158/1055-9965.EPI-19-0755DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7571256PMC
February 2020

Multi-ancestry sleep-by-SNP interaction analysis in 126,926 individuals reveals lipid loci stratified by sleep duration.

Nat Commun 2019 11 12;10(1):5121. Epub 2019 Nov 12.

Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, Netherlands.

Both short and long sleep are associated with an adverse lipid profile, likely through different biological pathways. To elucidate the biology of sleep-associated adverse lipid profile, we conduct multi-ancestry genome-wide sleep-SNP interaction analyses on three lipid traits (HDL-c, LDL-c and triglycerides). In the total study sample (discovery + replication) of 126,926 individuals from 5 different ancestry groups, when considering either long or short total sleep time interactions in joint analyses, we identify 49 previously unreported lipid loci, and 10 additional previously unreported lipid loci in a restricted sample of European-ancestry cohorts. In addition, we identify new gene-sleep interactions for known lipid loci such as LPL and PCSK9. The previously unreported lipid loci have a modest explained variance in lipid levels: most notable, gene-short-sleep interactions explain 4.25% of the variance in triglyceride level. Collectively, these findings contribute to our understanding of the biological mechanisms involved in sleep-associated adverse lipid profiles.
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http://dx.doi.org/10.1038/s41467-019-12958-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6851116PMC
November 2019

Personal Characteristics Effects on Validation of Self-reported Type 2 Diabetes From a Cross-sectional Survey Among Chinese Adults.

J Epidemiol 2020 Nov 26;30(11):516-521. Epub 2019 Oct 26.

State Key Laboratory of Oncogenes and Related Genes & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine.

Background: The objective was to evaluate the effects of personal characteristics on the validation of self-reported type 2 diabetes among Chinese adults in urban Shanghai.

Methods: During 2015 through 2016, 4,322 participants were recruited in this validation study. We considered the criteria of diabetes verification to use the laboratory assays of fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), or self-reported use of diabetic medication.

Results: When taking diabetic medication or FPG ≥7.0 mmol/L was as identified diabetes, the measurements of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and Kappa value of self-reported diabetes were 72.0%, 99.2%, 95.1%, 93.9%, and 0.78, respectively. If an additional HbA1c test was used for 708 subjects (aged <65 years), slightly lower values of sensitivity, NPV, and Kappa were observed. More potential diabetes cases were found compared to only using FPG. Subjects who were female, older, or had a family history of diabetes had sensitivity over 75% and excellent Kappa over 0.8, while the sensitivity and Kappa of opposite groups had poorer values. Specificity, PPV, and NPV were similar among groups with different demographic or disease characteristics. The prevalence of type 2 diabetes was 19.3% in the study (14.1% diagnosed diabetes, 5.2% undiagnosed diabetes). About 26.2% of subjects were pre-diabetic. Additional HbA1c test indicated an increased prevalence of undiagnosed diabetes and pre-diabetes.

Conclusions: Findings support self-reported diabetes is sufficiently valid to be used in large-scale, population-based epidemiologic studies. Participants with different characteristics may have different indicators in terms of validation, such as age, gender, and family history of diabetes in first-degree relatives.
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http://dx.doi.org/10.2188/jea.JE20190178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7557172PMC
November 2020

Association of Dietary Fiber and Yogurt Consumption With Lung Cancer Risk: A Pooled Analysis.

JAMA Oncol 2020 02 13;6(2):e194107. Epub 2020 Feb 13.

Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, Nashville, Tennessee.

Importance: Dietary fiber (the main source of prebiotics) and yogurt (a probiotic food) confer various health benefits via modulating the gut microbiota and metabolic pathways. However, their associations with lung cancer risk have not been well investigated.

Objective: To evaluate the individual and joint associations of dietary fiber and yogurt consumption with lung cancer risk and to assess the potential effect modification of the associations by lifestyle and other dietary factors.

Design, Setting, And Participants: This pooled analysis included 10 prospective cohorts involving 1 445 850 adults from studies that were conducted in the United States, Europe, and Asia. Data analyses were performed between November 2017 and February 2019. Using harmonized individual participant data, hazard ratios and 95% confidence intervals for lung cancer risk associated with dietary fiber and yogurt intakes were estimated for each cohort by Cox regression and pooled using random-effects meta-analysis. Participants who had a history of cancer at enrollment or developed any cancer, died, or were lost to follow-up within 2 years after enrollment were excluded.

Exposures: Dietary fiber intake and yogurt consumption measured by validated instruments.

Main Outcomes And Measures: Incident lung cancer, subclassified by histologic type (eg, adenocarcinoma, squamous cell carcinoma, and small cell carcinoma).

Results: The analytic sample included 627 988 men, with a mean (SD) age of 57.9 (9.0) years, and 817 862 women, with a mean (SD) age of 54.8 (9.7) years. During a median follow-up of 8.6 years, 18 822 incident lung cancer cases were documented. Both fiber and yogurt intakes were inversely associated with lung cancer risk after adjustment for status and pack-years of smoking and other lung cancer risk factors: hazard ratio, 0.83 (95% CI, 0.76-0.91) for the highest vs lowest quintile of fiber intake; and hazard ratio, 0.81 (95% CI, 0.76-0.87) for high vs no yogurt consumption. The fiber or yogurt associations with lung cancer were significant in never smokers and were consistently observed across sex, race/ethnicity, and tumor histologic type. When considered jointly, high yogurt consumption with the highest quintile of fiber intake showed more than 30% reduced risk of lung cancer than nonyogurt consumption with the lowest quintile of fiber intake (hazard ratio, 0.67 [95% CI, 0.61-0.73] in total study populations; hazard ratio, 0.69 [95% CI, 0.54-0.89] in never smokers), suggesting potential synergism.

Conclusions And Relevance: Dietary fiber and yogurt consumption was associated with reduced risk of lung cancer after adjusting for known risk factors and among never smokers. Our findings suggest a potential protective role of prebiotics and probiotics against lung carcinogenesis.
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http://dx.doi.org/10.1001/jamaoncol.2019.4107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6813596PMC
February 2020

Re-evaluating genetic variants identified in candidate gene studies of breast cancer risk using data from nearly 280,000 women of Asian and European ancestry.

EBioMedicine 2019 Oct 16;48:203-211. Epub 2019 Oct 16.

Department of Epidemiology, Cancer Prevention Institute of California, Fremont, CA, USA; Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA, USA; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.

Background: We previously conducted a systematic field synopsis of 1059 breast cancer candidate gene studies and investigated 279 genetic variants, 51 of which showed associations. The major limitation of this work was the small sample size, even pooling data from all 1059 studies. Thereafter, genome-wide association studies (GWAS) have accumulated data for hundreds of thousands of subjects. It's necessary to re-evaluate these variants in large GWAS datasets.

Methods: Of these 279 variants, data were obtained for 228 from GWAS conducted within the Asian Breast Cancer Consortium (24,206 cases and 24,775 controls) and the Breast Cancer Association Consortium (122,977 cases and 105,974 controls of European ancestry). Meta-analyses were conducted to combine the results from these two datasets.

Findings: Of those 228 variants, an association was observed for 12 variants in 10 genes at a Bonferroni-corrected threshold of P < 2·19 × 10. The associations for four variants reached P < 5 × 10 and have been reported by previous GWAS, including rs6435074 and rs6723097 (CASP8), rs17879961 (CHEK2) and rs2853669 (TERT). The remaining eight variants were rs676387 (HSD17B1), rs762551 (CYP1A2), rs1045485 (CASP8), rs9340799 (ESR1), rs7931342 (CHR11), rs1050450 (GPX1), rs13010627 (CASP10) and rs9344 (CCND1). Further investigating these 10 genes identified associations for two additional variants at P < 5 × 10, including rs4793090 (near HSD17B1), and rs9210 (near CYP1A2), which have not been identified by previous GWAS.

Interpretation: Though most candidate gene variants were not associated with breast cancer risk, we found 14 variants showing an association. Our findings warrant further functional investigation of these variants. FUND: National Institutes of Health.
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http://dx.doi.org/10.1016/j.ebiom.2019.09.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6838373PMC
October 2019

Association of Untargeted Urinary Metabolomics and Lung Cancer Risk Among Never-Smoking Women in China.

JAMA Netw Open 2019 09 4;2(9):e1911970. Epub 2019 Sep 4.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland.

Importance: Chinese women have the highest rate of lung cancer among female never-smokers in the world, and the etiology is poorly understood.

Objective: To assess the association between metabolomics and lung cancer risk among never-smoking women.

Design, Setting, And Participants: This nested case-control study included 275 never-smoking female patients with lung cancer and 289 never-smoking cancer-free control participants from the prospective Shanghai Women's Health Study recruited from December 28, 1996, to May 23, 2000. Validated food frequency questionnaires were used for the collection of dietary information. Metabolomic analysis was conducted from November 13, 2015, to January 6, 2016. Data analysis was conducted from January 6, 2016, to November 29, 2018.

Exposures: Untargeted ultra-high-performance liquid chromatography-tandem mass spectrometry and nuclear magnetic resonance metabolomic profiles were characterized using prediagnosis urine samples. A total of 39 416 metabolites were measured.

Main Outcomes And Measures: Incident lung cancer.

Results: Among the 564 women, those who developed lung cancer (275 participants; median [interquartile range] age, 61.0 [52-65] years) and those who did not develop lung cancer (289 participants; median [interquartile range] age, 62.0 [53-66] years) at follow-up (median [interquartile range] follow-up, 10.9 [9.0-11.7] years) were similar in terms of their secondhand smoke exposure, history of respiratory diseases, and body mass index. A peak metabolite, identified as 5-methyl-2-furoic acid, was significantly associated with lower lung cancer risk (odds ratio, 0.57 [95% CI, 0.46-0.72]; P < .001; false discovery rate = 0.039). Furthermore, this peak was weakly correlated with self-reported dietary soy intake (ρ = 0.21; P < .001). Increasing tertiles of this metabolite were associated with lower lung cancer risk (in comparison with first tertile, odds ratio for second tertile, 0.52 [95% CI, 0.34-0.80]; and odds ratio for third tertile, 0.46 [95% CI, 0.30-0.70]), and the association was consistent across different histological subtypes and follow-up times. Additionally, metabolic pathway analysis found several systemic biological alterations that were associated with lung cancer risk, including 1-carbon metabolism, nucleotide metabolism, oxidative stress, and inflammation.

Conclusions And Relevance: This prospective study of the untargeted urinary metabolome and lung cancer among never-smoking women in China provides support for the hypothesis that soy-based metabolites are associated with lower lung cancer risk in never-smoking women and suggests that biological processes linked to air pollution may be associated with higher lung cancer risk in this population.
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http://dx.doi.org/10.1001/jamanetworkopen.2019.11970DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6755532PMC
September 2019

Association between educational level and total and cause-specific mortality: a pooled analysis of over 694 000 individuals in the Asia Cohort Consortium.

BMJ Open 2019 08 22;9(8):e026225. Epub 2019 Aug 22.

Armed Forces Capital Hospital, Seoul National University College of Medicine, Seoul, The Republic of Korea.

Objective: To study the association of educational level and risk of death from all causes, cardiovascular disease (CVD) and cancer among Asian populations.

Design: A pooled analysis of 15 population-based cohort studies.

Setting And Participants: 694 434 Asian individuals from 15 prospective cohorts within the Asia Cohort Consortium.

Interventions: None.

Main Outcome Measures: HRs and 95% CIs for all-cause mortality, as well as for CVD-specific mortality and cancer-specific mortality.

Results: A total of 694 434 participants (mean age at baseline=53.2 years) were included in the analysis. During a mean follow-up period of 12.5 years, 103 023 deaths were observed, among which 33 939 were due to cancer and 34 645 were due to CVD. Higher educational levels were significantly associated with lower risk of death from all causes compared with a low educational level (≤primary education); HRs and 95% CIs for secondary education, trade/technical education and ≥university education were 0.88 (0.85 to 0.92), 0.81 (0.73 to 0.90) and 0.71 (0.63 to 0.80), respectively (p=0.002). Similarly, HRs (95% CIs) were 0.93 (0.89 to 0.97), 0.86 (0.78 to 0.94) and 0.81 (0.73 to 0.89) for cancer death, and 0.88 (0.83 to 0.93), 0.77 (0.66 to 0.91) and 0.67 (0.58 to 0.77) for CVD death with increasing levels of education (both p <0.01). The pattern of the association among East Asians and South Asians was similar compared with ≤primary education; HR (95% CI) for all-cause mortality associated with ≥university education was 0.72 (0.63 to 0.81) among 539 724 East Asians (Chinese, Japanese and Korean) and 0.61 (0.54 to 0.69) among 154 710 South Asians (Indians and Bangladeshis).

Conclusion: Higher educational level was associated with substantially lower risk of death among Asian populations.
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http://dx.doi.org/10.1136/bmjopen-2018-026225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6707688PMC
August 2019

Plant and Animal Protein Intake and Risk of Incident Kidney Stones: Results from the Shanghai Men's and Women's Health Studies.

J Urol 2019 12 20;202(6):1217-1223. Epub 2019 Aug 20.

Department of Urology, Vanderbilt University Medical Center, Nashville, Tennessee.

Purpose: High animal protein intake is a risk factor for nephrolithiasis. Whether plant based sources of protein are associated with kidney stone risk is not well studied. We examined the association of animal and plant protein intake with the risk of incident kidney stones in Shanghai, China.

Materials And Methods: Dietary intakes were obtained from a validated food frequency questionnaire at baseline. Self-reported stone events were ascertained at baseline and at followup visits. Multivariable Cox regression models were used to evaluate the associations of protein intake with the incident stone risk.

Results: During 319,211 and 696,950 person-years of followup 1,451 men and 1,202 women, respectively, reported incident stones. The average ± SD intake of animal and plant protein standardized to 2,000 kcal was 31.3 ± 13.7 and 48.4 ± 7.2 gm per day in women, and 30.8 ± 13.3 and 51.3 ± 7.6 gm per day, respectively, in men. On multivariable analysis participants in the highest quintiles of animal and nondairy animal protein intake showed an increased risk of incident stones compared to those in the lowest quintiles (HR 1.16, 95% CI 1.01-1.32, p=0.03 vs HR 1.14, 95% CI 1.01-1.30, p=0.04). Compared to the lowest quintile the highest intake quintiles of the animal-to-plant protein ratios and the nondairy animal-to-plant protein ratios were positively associated with stone risk (HR 1.17, 95% CI 1.03-1.33, p=0.02 and HR 1.20, 95% CI 1.06-1.36, p=0.005, respectively). No association was observed with plant protein intake (p=0.14).

Conclusions: In this population with a relatively low animal protein intake and a high plant protein intake, a greater animal protein intake was associated with a kidney stone risk. Increasing the proportion of plant protein relative to animal protein appeared protective against the risk.
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http://dx.doi.org/10.1097/JU.0000000000000493DOI Listing
December 2019

Association of BMI, Smoking, and Alcohol with Multiple Myeloma Mortality in Asians: A Pooled Analysis of More than 800,000 Participants in the Asia Cohort Consortium.

Cancer Epidemiol Biomarkers Prev 2019 11 9;28(11):1861-1867. Epub 2019 Aug 9.

Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore.

Background: To date, few epidemiologic studies have been conducted to elucidate lifestyle-related risk factors for multiple myeloma in Asia. We investigated the association of body mass index (BMI), smoking, and alcohol intake with the risk of multiple myeloma mortality through a pooled analysis of more than 800,000 participants in the Asia Cohort Consortium.

Methods: The analysis included 805,309 participants contributing 10,221,623 person-years of accumulated follow-up across Asia Cohort Consortium cohorts. HRs and 95% confidence intervals (95% CI) for the association between BMI, smoking, and alcohol at baseline and the risk of multiple myeloma mortality were assessed using a Cox proportional hazards model with shared frailty.

Results: We observed a statistically significant dose-dependent association between BMI categories and the risk of multiple myeloma mortality (<18.5 kg/m: HR = 0.80, 95% CI: 0.52-1.24; 18.5-24.9 kg/m: reference; 25.0-29.9 kg/m: HR = 1.17, 95% CI: 0.94-1.47; ≥30 kg/m: HR = 1.61, 95% CI: 0.99-2.64, = 0.014). By sex, this association was more apparent in women than in men (P for heterogeneity between sexes = 0.150). We observed no significant associations between smoking or alcohol consumption and risk of multiple myeloma mortality.

Conclusions: This study showed that excess body mass is associated with an increased risk of multiple myeloma mortality among Asian populations. In contrast, our results do not support an association between smoking or alcohol consumption and the risk of multiple myeloma mortality in Asian populations.

Impact: This study provides important evidence on the association of BMI, smoking, and alcohol with the risk of multiple myeloma mortality in Asian populations.
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http://dx.doi.org/10.1158/1055-9965.EPI-19-0389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7986478PMC
November 2019
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