Publications by authors named "Jin-Hu Fan"

92 Publications

Comparisons of Treatment for HER2-Positive Breast Cancer between Chinese and International Practice: A Nationwide Multicenter Epidemiological Study from China.

J Oncol 2021 15;2021:6621722. Epub 2021 Sep 15.

Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Objective: To better understand the status of medical treatment for human epidermal growth factor receptor 2 (HER2)-positive breast cancer and the differences between the Chinese and the international clinical practice.

Methods: This was a retrospective, nationwide, multicenter, epidemiological study of advanced breast cancer patients from China. Between January 01, 2012, and December 31, 2014, a total of 3649 patients, covering 7 geographic regions and 21 institutions, participated in this series of studies. HER2-positive breast cancer was selected among the group and adopted into this study. In comparison, we summarized the demographics and clinical characteristics of HER2-positive breast cancer from the Surveillance, Epidemiology, and End Results (SEER) database.

Results: A total of 918 patients diagnosed as HER2-positive breast cancer patients were included. The median age at diagnosis was 46 years (ranging, 23 to 78) with a single-peak incidence. The proportions of stages II-IV at diagnosis and distance metastasis in viscera were more than half of the participants. In comparison, the prevalence of estrogen or progesterone receptor-positive expression and luminalB subtype was relatively lower than that of the United States. The receipt of chemotherapy was fairly higher, while the usage of targeted therapy was seriously insufficient. Tumor size was in significantly positive associations with the duration of targeted therapy (Kendall's correlation coefficient = 0.3, < 0.0001), while no prohibitive variables among clinical characteristics were detected.

Conclusion: Our study suggested that HER2-positive breast cancer patients were characterized as a younger trend, a lower prevalence of hormonal receptor (HR)-positive expression, and less accessible to anti-HER2 targeted therapy with insufficient duration over the past few years in China. Concerted efforts should be exerted for promising survival benefits in the future. The trial registration number is https://clinicaltrials.gov/ct2/show/NCT03047889.
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http://dx.doi.org/10.1155/2021/6621722DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8457988PMC
September 2021

Colorectal cancer in the Linxian China Nutrition Intervention Trial: Risk factors and intervention results.

PLoS One 2021 15;16(9):e0255322. Epub 2021 Sep 15.

Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States of America.

Background: Colorectal cancer (CRC) is among the most common cancers in economically developed countries and developing world. While dietary factors are associated with risk of CRC in the West and urban China, little is known about risk or protective factors in rural China.

Methods: The Linxian General Population Nutrition Intervention Trial (NIT) cohort was established over 30 years ago to test whether daily multivitamin/mineral supplements could reduce the incidence and mortality of esophageal/gastric cardia cancer. The cohort included a total of 29,553 healthy participants 40-69 years old who were randomly assigned to supplements or placebos via a 24 fractional factorial study design. We examined risk factors for the development of CRC as well as the effects of four different nutritional factors (Factor A: retinol, zinc; B: riboflavin, niacin; C: ascorbic acid, molybdenum; D: selenium, alpha-tocopherol, beta-carotene,) on CRC incidence following 5.25 years of supplementation in this randomized, placebo-controlled intervention trial.

Results: CRC risk increased with age and height as well as piped water usage, family history of CRC, and consumption of foods cooked in oil, eggs, and fresh fruits. No effect on CRC was seen for any of these four intervention factors tested in both genders, but CRC was reduced 37% in females who received Factor D (selenium/alpha-tocopherol/beta-carotene) (RR = 0.63, 95% CI = 0.43-0.92, P = 0.016) compared to females who did not receive Factor D.

Conclusions: In this undernourished rural Chinese population, CRC risk factors in this Chinese cohort showed both similarities and differences compared to Western and urban Asian Chinese populations. Intervention results suggested a potential benefit for women supplemented with selenium/alpha-tocopherol/beta-carotene.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0255322PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8443060PMC
September 2021

Family History and Risk of Upper Gastrointestinal Cancer in the Linxian General Population.

Front Oncol 2021 28;11:605106. Epub 2021 May 28.

Metabolic Epidemiology Branch, Division of Cancer Epidemiology & Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States.

Objective: The objective of this study was to investigate family history (FH) of upper gastrointestinal (UGI) cancer and risk of esophageal squamous cell carcinoma (ESCC), gastric cardia carcinoma (GCC), and gastric non-cardia carcinoma (GNCC) in the Linxian General Population Nutrition Intervention Trial (NIT) cohort. Methods: This prospective analysis was conducted using the Linxian NIT cohort data. Subjects with FH of UGI cancer was treated as an exposed group while the remainders were considered as a comparison group. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between FH of UGI cancer and risk of UGI cancer incidence and mortality were estimated using Cox proportional hazards models.

Results: There were 5,680 newly diagnosed UGI cancer cases during the follow-up period, with a total of 4,573 UGI cancer deaths occurred, including 2,603 ESCC, 1,410 GCC, and 560 GNCC deaths. A positive FH of UGI cancer was associated with a significantly increased risk of ESCC and GCC (Incidence: HR = 1.45, 95%CI: 1.35-1.56; HR = 1.27, 95%CI: 1.15-1.40; Mortality: HR = 1.40, 95%CI: 1.30-1.52; HR = 1.27, 95%CI: 1.14-1.42) after adjusting for age at baseline, gender, smoking status, alcohol drinking, education level, and frequency of fresh fruit and vegetable consumption. Subjects with FH in both parents had the highest risk of ESCC and GCC incidence (HR = 1.65, 95%CI: 1.40-1.95; HR = 1.42, 95%CI: 1.12-1.81) and deaths (HR = 1.65, 95%CI: 1.38-1.97; HR = 1.42, 95%CI: 1.09-1.85). Spouse diagnosed with UGI cancer did not increase the risk of any UGI cancers of the subjects. In subgroup analysis, FH of UGI cancer was shown to significantly increase the risk of GCC in non-drinkers (Incidence: HR = 1.31, 95%CI: 1.17-1.47; Mortality: HR = 1.33, 95%CI: 1.17-1.50). No associations were observed for risk of GNCC. Sensitivity analysis by excluding subjects who were followed up less than three years did not materially alter our results.

Conclusion: Our data point to the role of the FH of UGI cancer to the risk of ESCC and GCC incidence and mortality. The influence of family history on the risk of UGI cancer varies from different types of family members.
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http://dx.doi.org/10.3389/fonc.2021.605106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193945PMC
May 2021

ABO genotypes and the risk of esophageal and gastric cancers.

BMC Cancer 2021 May 22;21(1):589. Epub 2021 May 22.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 9609 Medical Center Dr. 6E3280, Rockville, MD, 20850, USA.

Background: Blood type has been associated with the risk of gastric cancer, but few studies have examined the association with esophageal squamous cell carcinoma (ESCC).

Methods: We conducted a case-control study using genotyping data of Chinese individuals, including cases of 2022 ESCC, 1189 gastric cardia adenocarcinoma, 1161 gastric noncardia adenocarcinoma, and 2696 controls. Genetic blood type was imputed using three single nucleotide polymorphisms. We used logistic regression to examine the association between blood type and the risk of each cancer.

Results: Compared to blood type O, the risk of ESCC was significantly elevated for blood type B and AB, with the highest risk for type AB (OR, 95%CI: 1.34, 1.07-1.67). Analysis of genotype suggested that the association of ESCC was from carrying the B allele. Similarly, blood type was significantly associated with gastric noncardia adenocarcinoma (P < 0.001) with risk significantly elevated in type A (1.37, 1.14-1.65) and AB (1.44, 1.10-1.89) compared to type O. Blood type was not associated with gastric cardia adenocarcinoma (P = 0.13).

Conclusions: This study provides novel insights into the association between blood type and the risk of ESCC and restricted previously observed association to only gastric noncardia cancer, providing important evidence to clarify the pattern of association and suggesting mechanisms of action.
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http://dx.doi.org/10.1186/s12885-021-08334-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141232PMC
May 2021

Clinical characteristics, medical service utilization, and expenditure for colorectal cancer in China, 2005 to 2014: Overall design and results from a multicenter retrospective epidemiologic survey.

Cancer 2021 Jun 30;127(11):1880-1893. Epub 2021 Mar 30.

Department of Cancer Prevention, Anhui Cancer Hospital, Hefei, China.

Background: Colorectal cancer (CRC) is the third most common cancer in China, however, publicly available, descriptive information on the clinical epidemiology of CRC is limited.

Methods: Patients diagnosed with primary CRC during 2005 through 2014 were sampled from 13 tertiary hospitals in 9 provinces across China. Data related to sociodemographic characteristics, the use of diagnostic technology, treatment adoption, and expenditure were extracted from individual medical records.

Results: In the full cohort of 8465 patients, the mean ± SD age at diagnosis was 59.3 ± 12.8 years, 57.2% were men, and 58.7% had rectal cancer. On average, 14.4% of patients were diagnosed with stage IV disease, and this proportion increased from 13.5% in 2005 to 20.5% in 2014 (P value for trend < .05). For diagnostic techniques, along with less use of x-rays (average, 81.6%; decreased from 90.0% to 65.7%), there were increases in the use of computed tomography (average, 70.4%; increased from 4.5% to 90.5%) and magnetic resonance imaging (average, 8.8%; increased from 0.1% to 20.4%) over the study period from 2005 to 2014. With regard to treatment, surgery alone was the most common (average, 50.1%), but its use decreased from 51.3% to 39.8% during 2005 through 2014; and the use of other treatments increased simultaneously, such as chemotherapy alone (average, 4.1%; increased from 4.1% to 11.9%). The average medical expenditure per patient was 66,291 Chinese Yuan (2014 value) and increased from 47,259 to 86,709 Chinese Yuan.

Conclusions: The increasing proportion of late-stage diagnoses presents a challenge for CRC control in China. Changes in diagnostic and treatment options and increased expenditures are clearly illustrated in this study. Coupled with the recent introduction of screening initiatives, these data provide an understanding of changes over time and may form a benchmark for future related evaluations of CRC interventions in China.
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http://dx.doi.org/10.1002/cncr.33445DOI Listing
June 2021

Serum Levels of Androgens, Estrogens, and Sex Hormone Binding Globulin and Risk of Primary Gastric Cancer in Chinese Men: A Nested Case-Control Study.

Cancer Prev Res (Phila) 2021 Jun 25;14(6):659-666. Epub 2021 Mar 25.

Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland.

Gastric cancer shows a strong male predominance, and sex steroid hormones have been hypothesized to explain this sex disparity. Previous studies examining the associations between sex hormones and sex hormone binding globulin (SHBG) and risk of gastric cancer come primarily from western populations and additional studies in diverse populations will help us better understand the association. We performed a nested case-control study in Linxian Nutrition Intervention Trials cohorts to evaluate the associations among Chinese men, where we had sufficient cases to perform a well-powered study. Using radioimmunoassays and immunoassays, we quantitated androgens, estrogens, and SHBG in baseline serum from 328 men that developed noncardia gastric cancer and matched controls. We used multivariable unconditional logistic regression to calculate ORs and 95% confidence intervals (CI) and explored interactions with body mass index (BMI), age, alcohol drinking, smoking, and follow-up time. Subjects with SHBG in the highest quartile, as compared with those in the lowest quartile, had a significantly increased risk of gastric cancer (OR = 1.87; 95% CI, 1.01-3.44). We found some evidence for associations of sex steroid hormones in men with lower BMI. Our study found a novel association suggesting that higher serum concentrations of SHBG may be associated with risk of gastric cancer in men. We found no overall associations with sex hormones themselves, but future studies should expand the scope of these studies to include women and further explore whether BMI modifies a potential association. PREVENTION RELEVANCE: It was the first study to investigate the association of gastric cancer with prediagnostic sex steroid hormones and SHBG in an Asian male population. Although there were no overall associations for sex steroid hormone concentrations, higher concentrations of SHBG was associated with increased risk of noncardia gastric cancer.
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http://dx.doi.org/10.1158/1940-6207.CAPR-20-0497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8225565PMC
June 2021

Clinicopathological characteristics and treatment of young women with breast cancer in China: a nationwide multicenter 10-year retrospective study.

Gland Surg 2021 Jan;10(1):175-185

Department of Medical Oncology, Cancer Institute & Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

Background: Breast cancer is currently the most common female malignancy in China. However, the clinical features and overall prognosis of young women diagnosed with this malignancy remain unclear. This study aimed to describe the clinicopathological characteristics of young patients (≤34 years of age) with breast cancer and explore the current treatment approaches used in China.

Methods: This was a hospital-based, multicenter, retrospective study of women with breast cancer across seven Chinese hospitals from 1999 to 2008. A total of 295 young (≤34 years of age) patients (research group) and 2,119 women aged 35 to 49 years (control group) were included in the study. Patient epidemiology, pre-operative examinations, clinical pathology, and treatment were analyzed.

Results: The percentage of young patients with breast cancer in the study group was 7.01%. These young women had a lower body mass index (BMI), a higher level of education, a lower number of previous births, and a lower history of breastfeeding than the control group (P<0.05). Increasingly, pre-operative use of ultrasound and magnetic resonance imaging are being used to diagnose breast cancer in young women in China. In young women with breast cancer, breast cancer not otherwise specified (NOS) was the primary pathology. The carcinoma in young women was more prone to lymph node metastasis, showed less progesterone receptor (PR) expression, and was more advanced than observed in the control group (P<0.05). We found that the number of young breast cancer patients undergoing breast-conserving surgery in China is increasing.

Conclusions: Young breast cancer patients display unique clinicopathological features, including tumors of a higher grade than those aged 35 years or older. As breast cancer is more aggressive in younger women, prevention and early diagnosis are critical, and new policies should be developed in line with these findings.
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http://dx.doi.org/10.21037/gs-20-574DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882316PMC
January 2021

Independent and Joint Associations between Serum Calcium, 25-Hydroxy Vitamin D, and the Risk of Primary Liver Cancer: A Prospective Nested Case-Control Study.

Cancer Epidemiol Biomarkers Prev 2020 10 20;29(10):2057-2064. Epub 2020 Aug 20.

Department of Cancer Epidemiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: Accumulating evidence has shown that serum calcium and vitamin D may be associated with or influence various cancer risks. However, no prospective studies have evaluated the independent and joint associations between prediagnostic levels of serum calcium and vitamin D and future risk of incident primary liver cancer.

Methods: We used a nested case-control design to evaluate subjects over 22 years of follow-up. Serum calcium, 25-hydroxy vitamin D [25(OH)D], and three markers of hepatitis B virus and hepatitis C virus were measured in baseline serum from 226 incident primary liver cancer cases and 1,061 matched controls. We calculated ORs and 95% confidence intervals (CI) using logistic regression to estimate the associations between calcium, 25(OH)D, and primary liver cancer risk.

Results: Multivariable adjusted models showed that subjects with both low (OR = 1.48, 95% CI = 1.01-2.17) or high (OR = 1.92, 95% CI = 1.34-2.76) calcium had an increased primary liver cancer risk, while those with high 25(OH)D had a decreased risk of primary liver cancer (OR = 0.54, 95% CI = 0.35-0.82). In joint analyses, when compared with subjects with medium calcium and 25(OH)D, subjects with high calcium and medium 25(OH)D had elevated odds of developing primary liver cancer (OR = 1.89, 95% CI = 1.17-3.05); those with medium calcium and high 25(OH)D had reduced odds of developing primary liver cancer (OR = 0.34, 95% CI = 0.17-0.67); and subjects in other classifications of calcium and serum 25(OH)D levels had no change in the odds of developing primary liver cancer (all > 0.05).

Conclusions: In a nutrient-deficient population, we found that serum calcium and serum 25(OH)D could potentially be modifiable risk or protective factors.

Impact: Our findings provide potential targets for primary liver cancer prevention and control.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-0417DOI Listing
October 2020

Profile and outcome of receptor conversion in breast cancer metastases: a nation-wide multicenter epidemiological study.

Int J Cancer 2021 02 19;148(3):692-701. Epub 2020 Aug 19.

Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Although receptor status including estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) of the primary breast tumors was related to the prognosis of breast cancer patients, little information is yet available on whether patient management and survival are impacted by receptor conversion in breast cancer metastases. Using data from the nation-wide multicenter clinical epidemiology study of advanced breast cancer in China (NCT03047889), we report the situation of retesting ER, PR and HER2 status for breast cancer metastases and evaluate the patient management and prognostic value of receptor conversion. In total, 3295 patients were analyzed and 1583 (48.0%) patients retesting receptor status for metastasis. Discordance in one or more receptors between the primary and the metastatic biopsy was found in 37.7% of women. Patients who remained hormone receptor (HR) positive in their metastases had similar progression-free survival of first-line and second-line treatment compared to patients with HR conversion (P > .05). In multivariate analysis, patients who showed ER conversion from negative to positive had longer disease-free survival (DFS) than patients who remained negative in their metastases (hazard ratio, 2.05; 95% confidence interval [CI], 1.45-2.90; P < .001). Patients with PR remained positive and had longer DFS than patients with PR conversion from negative to positive (hazard ratio, 0.56; 95% CI, 0.38-0.83; P = .004). Patients with PR conversion have shorter overall survival than patients with PR remained positive or negative (P = .016 and P = .041, respectively). Our findings showed that the receptors' conversions were common in metastatic breast cancer, and the conversion impacted the survival.
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http://dx.doi.org/10.1002/ijc.33227DOI Listing
February 2021

Body mass index and risk of upper gastrointestinal cancer: A 30-year follow-up of the Linxian dysplasia nutrition intervention trial cohort.

Cancer Epidemiol 2020 04 9;65:101683. Epub 2020 Feb 9.

Metabolic Epidemiology Branch, Division of Cancer Epidemiology & Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.

Background: Although a number of previous studies have noted the association between body mass index (BMI) and upper gastrointestinal (UGI) cancer risk, little evidence exists in the Chinese esophageal squamous dysplasia population. This prospective study investigated the association between BMI and UGI cancer risk in the Linxian Dysplasia Nutrition Intervention Trial (NIT) cohort.

Methods: A total of 3298 participants were included in the final analysis. Asian-specific BMI cut-offs were used to define BMI subgroups: underweight <18.5 kg/m, normal ≥18.5 to <24 kg/m and overweight or obese ≥24 kg/m. Hazard ratios (HRs) and 95 % confidence intervals (95 %CIs) were estimated using the Cox proportional hazard model.

Results: During over 30 years of follow-up we identified 654 incident esophageal squamous-cell carcinoma (ESCC) cases and 434 gastric cancer cases which included 88 gastric non-cardia carcinoma (GNCC) and 346 gastric cardia carcinoma (GCC) cases. Relative to normal weight, overweight or obesity were associated with a significantly reduced risk of ESCC (HR 0.69, 95 %CI 0.48-0.98) after multivariate adjustment, including age at baseline, gender, smoking, drinking, family history of cancer, education and consumption of fresh fruit. Subgroup analyses found that clear effects were evident in women and subjects with a family history of cancer. No association with gastric cancer was observed in any subjects or subgroups.

Conclusion: Overweight/obesity was associated with decreased risk of ESCC in this dysplasia population, particularly in women and persons who had a family history of cancer. Future studies are needed to confirm these findings.
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http://dx.doi.org/10.1016/j.canep.2020.101683DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7276490PMC
April 2020

Serologic Profile of Antiparietal Cell Antibodies, Pepsinogens, and and Risk of Upper Gastrointestinal Cancer: A Nested Case-Control Study in China.

Cancer Epidemiol Biomarkers Prev 2019 12 9;28(12):2022-2029. Epub 2019 Sep 9.

Metabolic Epidemiology Branch, Division of Cancer Epidemiology & Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland.

Background: Autoimmune gastritis is understudied and possibly associated with gastric noncardia adenocarcinoma (GNCA) and esophageal squamous cell carcinoma (ESCC) in Western populations when it presents as pernicious anemia.

Methods: A nested case-control study within a Chinese cohort included 100 ESCC, 200 gastric cardia adenocarcinoma (GCA), and 200 GNCA cases diagnosed between 1986 and 2001 and 400 controls. Serostatus of antiparietal cell antibodies (APCA), antibodies, and pepsinogens were measured using commercial kits and serum collected at baseline. We used logistic regression to calculate odds ratios (OR) and 95% confidence interval (CI) for associations between serologic biomarkers and cancer risk adjusted for numerous potential confounders.

Results: There was an average interval of 8 years between baseline blood draw and cancer diagnosis. The baseline prevalence of APCA seropositivity was 10.0% and 14.5% in subjects who developed GCA and GNCA, respectively. APCA seropositivity was inversely associated with later development of GCA (OR = 0.42; 95% CI, 0.24-0.75), but not significantly associated with later development of GNCA (OR = 0.82; 95% CI, 0.50-1.36) or ESCC (OR = 1.05; 95% CI, 0.58-1.88). APCA seropositivity was significantly associated with low pepsinogen I/II ratios (OR = 3.69; 95% CI, 1.66-8.21), and individuals with low pepsinogen I/II ratios who were seronegative for APCA had the highest risk of both GCA and GNCA.

Conclusions: APCA seropositivity measured years prior to diagnosis was associated with prevalent atrophic gastritis but inversely associated with incident GCA in this Chinese population.

Impact: APCA may contribute to a growing list of serologic markers that can improve risk stratification for gastric cancer.
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http://dx.doi.org/10.1158/1055-9965.EPI-19-0512DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6891191PMC
December 2019

Serum ghrelin and esophageal and gastric cancer in two cohorts in China.

Int J Cancer 2020 05 12;146(10):2728-2735. Epub 2019 Aug 12.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD.

Ghrelin is a hormone produced in the oxyntic glands of the stomach. Previous work by our group has suggested that serum ghrelin concentrations are inversely associated with gastric and esophageal cancer risk. We measured ghrelin concentrations in the Linxian General Population Nutrition Intervention Trial (NIT), and the Shanghai Women's Health Study (SWHS). In NIT, we analyzed serum samples from 298 esophageal squamous cell carcinoma (ESCC) cases, 518 gastric cardia adenocarcinoma (GCA) cases, 258 gastric noncardia adenocarcinoma (GNCA) cases and 770 subcohort controls (case-cohort). In SWHS, we measured ghrelin in plasma samples from 249 GNCA cases and 498 matched controls (nested case-control). Ghrelin was measured using radioimmunoassay. In NIT and SWHS, low ghrelin concentrations were associated with an increased risk of developing GNCA and GCA. The hazard ratio (HR ) for GNCA in NIT was 1.35 (95% CI: 0.89-2.05; p-trend = 0.02); the odds ratio in SWHS was 1.66 (95% CI: 1.02-2.70; p-trend = 0.06). Low ghrelin was associated with a twofold increase of GCA (HR = 2.00, 95% CI: 1.45-2.77; p-trend<0.001). In contrast, a lower risk of ESCC (NIT ESCC HR = 0.65, 95% CI: 0.45-0.92; p-trend = 0.02) was found in NIT. Low baseline ghrelin concentrations were associated with an increased risk for GNCA and GCA in the NIT and the SWHS. In contrast, low ghrelin concentrations at baseline were associated with a reduced risk of developing ESCC in the NIT. Ghrelin may be an early marker of future cancer risk for developing upper gastrointestinal cancer in regions of high incidence.
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http://dx.doi.org/10.1002/ijc.32597DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7477842PMC
May 2020

Association of Diabetes With All-Cause and Cause-Specific Mortality in Asia: A Pooled Analysis of More Than 1 Million Participants.

JAMA Netw Open 2019 04 5;2(4):e192696. Epub 2019 Apr 5.

Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.

Importance: Asia is home to the largest diabetic populations in the world. However, limited studies have quantified the association of diabetes with all-cause and cause-specific mortality in Asian populations.

Objectives: To evaluate the association of diabetes with all-cause and cause-specific mortality in Asia and to investigate potential effect modifications of the diabetes-mortality associations by participants' age, sex, education level, body mass index, and smoking status.

Design, Setting, And Participants: This pooled analysis incorporated individual participant data from 22 prospective cohort studies of the Asia Cohort Consortium conducted between 1963 and 2006. A total of 1 002 551 Asian individuals (from mainland China, Japan, South Korea, Singapore, Taiwan, India, and Bangladesh) were followed up for more than 3 years. Cohort-specific hazard ratios and 95% confidence intervals for all-cause and cause-specific mortality were estimated using Cox regression models and then pooled using random-effects meta-analysis. Analysis was conducted between January 10, 2018, and August 31, 2018.

Exposures: Doctor-diagnosed diabetes, age, sex, education level, body mass index, and smoking status.

Main Outcomes And Measures: All-cause and cause-specific mortality.

Results: Of 1 002 551 participants (518 537 [51.7%] female; median [range] age, 54.0 [30.0-98.0] years), 148 868 deaths were ascertained during a median (range) follow-up of 12.6 (3.0-38.9) years. The overall prevalence of diabetes reported at baseline was 4.8% for men and 3.6% for women. Patients with diabetes had a 1.89-fold risk of all-cause death compared with patients without diabetes (hazard ratio [HR], 1.89; 95% CI, 1.74-2.04), with the highest relative risk of death due to diabetes itself (HR, 22.8; 95% CI, 18.5-28.1), followed by renal disease (HR, 3.08; 95% CI, 2.50-3.78), coronary heart disease (HR, 2.57; 95% CI, 2.19-3.02), and ischemic stroke (HR, 2.15; 95% CI, 1.85-2.51). The adverse diabetes-mortality associations were more evident among women (HR, 2.09; 95% CI, 1.89-2.32) than among men (HR, 1.74; 95% CI, 1.62-1.88) (P for interaction < .001) and more evident among adults aged 30 to 49 years (HR, 2.43; 95% CI, 2.08-2.84) than among adults aged 70 years and older (HR, 1.51; 95% CI, 1.40-1.62) (P for interaction < .001). A similar pattern of association was found between diabetes and cause-specific mortality, with significant variations noted by sex and age.

Conclusions And Relevance: This study found that diabetes was associated with increased risk of death from several diseases among Asian populations. Development and implementation of diabetes management programs are urgently needed to reduce the burden of diabetes in Asia.
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http://dx.doi.org/10.1001/jamanetworkopen.2019.2696DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6481439PMC
April 2019

Association between tooth loss and upper gastrointestinal cancer: A 30-year follow-up of the Linxian Dysplasia Nutrition Intervention Trial Cohort.

Thorac Cancer 2019 04 18;10(4):966-974. Epub 2019 Mar 18.

Metabolic Epidemiology Branch, Division of Cancer Epidemiology & Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.

Background: This prospective study investigated the association between tooth loss and upper gastrointestinal (UGI) cancer mortality in the Linxian Dysplasia Nutrition Intervention Trial Cohort.

Methods: Subjects were categorized into three groups according to age at baseline. No missing teeth and less or greater than median tooth loss in each group was defined as none, moderate, and severe, respectively. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated using the Cox proportional hazard model.

Results: Through 30 September 2015, 541 esophageal squamous cell carcinoma (ESCC), 284 gastric cardia carcinoma (GCC), and 77 gastric non-cardia carcinoma (GNCC) deaths occurred. In the six-year follow-up, severe tooth loss was associated with an increased risk of GCC mortality (HR 1.55, 95% CI 1.06-2.18). In the 15-year follow-up, moderate tooth loss increased the ESCC mortality risk by 58% (HR 1.58, 95% CI 1.06-2.35), while severe loss increased the GCC mortality risk by 30% (HR 1.30, 95% CI 1.03-1.64). In the 30-year follow-up, moderate tooth loss increased the risk of ESCC mortality (HR 1.34, 95% CI 1.01-1.76). In subjects aged < 55 at baseline and men, moderate tooth loss had 53% and 52% higher risks of ESCC mortality (HR 1.53, 95% CI 1.06-2.05; HRmen 1.52, 95% CI 1.01-2.28). No significant association was observed for GNCC in any subjects or subgroups.

Conclusion: Moderate tooth loss increased the risk of ESCC mortality, particularly in younger subjects and men. Severe tooth loss increased the risk of GCC mortality. Future studies are needed to confirm these findings.
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http://dx.doi.org/10.1111/1759-7714.13037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6449253PMC
April 2019

Clinical characteristics and medical service utilization of lung cancer in China, 2005-2014: Overall design and results from a multicenter retrospective epidemiologic survey.

Lung Cancer 2019 02 24;128:91-100. Epub 2018 Nov 24.

Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Electronic address:

Objectives: This study aimed to explore the clinical profile and its trajectory of lung cancer on clinicopathological characteristics and medical service utilization in China.

Methods: Patients diagnosed with primary lung cancer in tertiary hospitals during 2005-14 were selected from seven geographic regions of China. Data on clinical characteristics and medical service utilization was extracted from medical record, and the ten-year trends were explored.

Results: A total of 7184 patients were included, the mean age was 58.3 years and the male-to-female-ratio was 2.7. From 2005 to 2014, the proportion of ≥60 year-old patients increased from 41.2% to 56.2% (p < 0.001). The smoking rate decreased from 62.9% to 51.1% (p < 0.001) and the proportion of females increased from 23.5% to 31.9% (p < 0.001). The proportion of advanced stage increased from 41.9% to 47.4% (p < 0.001). Adenocarcinoma's proportion increased from 36.4% to 53.5% (p < 0.001) while that of squamous carcinoma decreased from 45.4% to 34.4% (p < 0.001). The application of chest X-ray dropped from 50.2% to 31.0% (p < 0.001) but that of chest CT increased from 65.8% to 81.4% (p < 0.001). As two main treatment options, chemotherapy (p = 0.290) and surgery (p = 0.497) remained stable. The medical expenditure per patient increased from 40,508 to 66,020 Chinese Yuan (p < 0.001).

Conclusions: The sustaining high smoking exposure, increasing proportion of female patients, advancing clinical stage, shifting of predominant pathology and increasing medical expenditure demonstrate potential challenges and directions on lung cancer prevention and control in China. Despite substantial changes of clinical characteristics, main treatment options remained unchanged, which needs further investigation.
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http://dx.doi.org/10.1016/j.lungcan.2018.11.031DOI Listing
February 2019

Association of tooth loss with liver cancer incidence and chronic liver disease mortality in a rural Chinese population.

PLoS One 2018 17;13(9):e0203926. Epub 2018 Sep 17.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, Maryland, United States of America.

Background: Tooth loss has been reported to be associated with the risk of liver cancer in several prior studies in economically advantaged countries. Whether this relationship is also evident in economically disadvantaged populations is not known.

Methods: We analyzed data from the Nutrition Intervention Trials, two randomized placebo-controlled trials of vitamin/mineral supplementation in Linxian, China. Participants who reported having lost permanent teeth were examined to determine the number of teeth remaining. In the 30-year follow-up period, 329 liver cancers were diagnosed and 368 chronic liver disease deaths occurred. Tooth loss was categorized based on loess smoothed age-specific predicted quartiles. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the two outcomes.

Results: Overall, persons in the highest quartile of age-specific tooth loss had an increased risk of liver cancer (HR = 1.27, 95%CI: 0.96, 1.67) which was not statistically significant. Results varied by sex and body mass index (BMI), however. Women in the highest quartile of age-specific tooth loss had a significantly increased risk (HR = 1.64, 95%CI: 1.04, 2.59), while men did not (HR = 1.08, 95%CI = 0.75, 1.57), and persons with a BMI > 23.0 kg/m2 (HR = 1.71, 95%CI: 1.00, 2.92) had a significantly increased risk, while persons with a BMI <23.0 kg/m2 did not (HR = 1.14, 95%CI: 0.82, 1.5). No relationships with chronic liver disease mortality were observed.

Conclusions: In a rural, economically disadvantaged population, persons with the highest levels of age-specific tooth loss had an increased risk of liver cancer. The results, which were stronger among women and persons with greater BMI, suggest that periodontal disease may increase risk of liver cancer.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0203926PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6141082PMC
March 2019

Association of plasma vitamin C concentration to total and cause-specific mortality: a 16-year prospective study in China.

J Epidemiol Community Health 2018 12 12;72(12):1076-1082. Epub 2018 Aug 12.

Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.

Background: Vitamin C insufficiency occurs across many countries and has been hypothesised to increase risk of various diseases. Few prospective studies with measured circulating vitamin C have related deficiency to disease mortality, particularly in low-income and middle-income countries.

Methods: We randomly selected 948 subjects (473 males and 475 females) aged 53-84 years from a Chinese cohort and measured meta-phosphoric acid-preserved vitamin C concentrations in plasma samples collected in 1999-2000. A total of 551 deaths were accrued from sample collection through 2016, including 141 from cancer, 170 from stroke and 174 from heart diseases. Vitamin C was analysed using season-specific quartiles, as a continuous variable and as a dichotomous variable based on sufficiency status (normal >28 µmol/L vs low ≤28 µmol/L). HRs and 95% CIs were estimated using Cox proportional hazards models.

Results: We found significant inverse associations between higher plasma vitamin C concentrations and total mortality in quartile (HR0.75, 95% CI 0.59 to 0.95), continuous (HR0.90, 95% CI 0.82 to 0.99) and dichotomous analyses (HR0.77, 95% CI 0.63 to 0.95). We observed significant lower risks of heart disease (p=0.03) and cancer deaths (p=0.04) for higher vitamin C, whereas the association was attenuated for stroke in adjusted models. Similar inverse associations were found when comparing normal versus low vitamin C for heart disease (HR0.62, 95% CI 0.42 to 0.89).

Conclusion: In this long-term prospective Chinese cohort study, higher plasma vitamin C concentration was associated with lower total mortality, heart disease mortality and cancer mortality. Our results corroborate the importance of adequate vitamin C to human health.
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http://dx.doi.org/10.1136/jech-2018-210809DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7579680PMC
December 2018

Longitudinal change in blood pressure is associated with cardiovascular disease mortality in a Chinese cohort.

Heart 2018 11 24;104(21):1764-1771. Epub 2018 Apr 24.

Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA.

Background: A number of studies have demonstrated a J-shaped curve between blood pressure (BP) and all-cause mortality, but few studies have used longitudinal change in BP to study mortality in the Chinese population.

Methods: We performed a 30-year follow-up study to examine the association between BP (at baseline and longitudinal change) and risk of mortality in the Linxian General Population Trial Cohort. At baseline, a total of 29 584 healthy adults were enrolled in the Linxian General Population Trial in 1985 and followed through to the end of 2014. The final analysis was restricted to 29 439 participants (55% women) after exclusion of outliers. We also examined the potential effects of BP trajectory patterns during the period of 1985-1999 on sequent risk of mortality. Adjusted Cox proportional hazards models were used to estimate HRs and 95% CIs.

Results: Compared with participants with normal BP, patients with prehypertension, stage 1, stage 2 or stage 3 hypertension had an increased risk of all-cause mortality, with HRs of 1.09 (95% CI 1.05 to 1.14), 1.34 (95% CI 1.28 to 1.40), 1.69 (95% CI 1.60 to 1.79) and 2.14 (95% CI 2.01 to 2.28), respectively. Relative to stable BP of normotension, having a rise in BP from normotension to hypertension or from prehypertension to hypertension both conferred an increased risk of total and cardiovascular disease and stroke mortality (total: HRs 1.22 (95% CI 1.12 to 1.34) and 1.36 (95% CI 1.23 to 1.51); cardiovascular disease: HRs 1.42 (95% CI 1.17 to 1.73) and 1.55 (95% CI 1.24 to 1.93); stroke: HRs 2.29 (95% CI 1.88 to 2.80) and 2.61 (95% CI 2.11 to 3.24), respectively).

Conclusions: These findings emphasise that development of incident hypertension in middle age could increase the risk of total, cardiovascular disease and stroke mortality, and suggest that current BP targets could be revised.

Trial Registration Number: NCT00342654;Post-results.
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http://dx.doi.org/10.1136/heartjnl-2017-312850DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6185795PMC
November 2018

Effects of Nutrition Intervention on Total and Cancer Mortality: 25-Year Post-trial Follow-up of the 5.25-Year Linxian Nutrition Intervention Trial.

J Natl Cancer Inst 2018 11;110(11):1229-1238

Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD.

Background: A beneficial effect of supplementation with selenium, vitamin E, and beta-carotene was observed on total and cancer mortality in a Chinese population, and it endured for 10 years postintervention, but longer durability is unknown.

Methods: A randomized, double-blind, placebo-controlled trial was conducted in Linxian, China, from 1986 to 1991; 29 584 residents age 40 to 69 years received daily supplementations based on a factorial design: Factors A (retinol/zinc), B (riboflavin/niacin), C (vitamin C/molybdenum), and/or D (selenium/vitamin E/beta-carotene), or placebo for 5.25 years, and followed for up 25 years. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the intervention effects on mortalities were estimated using Cox proportional hazards models.

Results: Through 2016, the interventions showed no effect on total mortality. The previously reported protective effect of Factor D against total mortality was lost 10 years postintervention. The protective effect of Factor D for gastric cancer was attenuated (HR = 0.93, 95% CI = 0.85 to 1.01), but a newly apparent protective effect against esophageal cancer was found for Factor B (HR = 0.92, 95% CI = 0.85 to 1.00, two-sided P = .04). Other protective/adverse associations were observed for cause-specific mortalities. Protective effects were found in people younger than age 55 years at baseline against non-upper gastrointestinal cancer death for Factor A (HR = 0.80, 95% CI = 0.69 to 0.92) and against death from stroke for Factor C (HR = 0.89, 95% CI = 0.82 to 0.96). In contrast, increased risk of esophageal cancer was found when the intervention began after age 55 years for Factors C (HR = 1.16, 95% CI = 1.04 to 1.30) and D (HR = 1.20, 95% CI = 1.07 to 1.34).

Conclusions: Multiyear nutrition intervention is unlikely to have a meaningful effect on mortality more than a decade after supplementation ends, even in a nutritionally deprived population. Whether sustained or repeat intervention would provide longer effects needs further investigation.
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http://dx.doi.org/10.1093/jnci/djy043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6235687PMC
November 2018

A nation-wide retrospective epidemiological study of gastroenteropancreatic neuroendocrine neoplasms in china.

Oncotarget 2017 Sep 3;8(42):71699-71708. Epub 2017 May 3.

Department of Cancer Epidemiology, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College.

Background: Representative data on the gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) in Asian patients is rare, especially in China. This study aims to create a GEP-NENs profile of Chinese patients.

Methods: This was a hospital-based, nation-wide, and multi-center 10-year (2001-2010) retrospective study which collected GEP-NEN patients' information in tertiary referral hospitals. All 2010 inpatient GEP-NEN cases with confirmed pathology in the selected hospitals were included. The primary GEP-NEN sites were measured and the epidemiological and clinical information of each tumor site were compared.

Results: The most common primary sites for GEP-NEN were the pancreas (31.5%) and rectum (29.6%), followed by the cardia (11.6%) and body (15.4%) of stomach. Small intestinal and colonic NENs took up a relatively small proportion of all patients. Pancreatic and rectal NENs, rather than cardiac and gastric body NENs, tended to be found in younger (<0.001), female (<0.001), urban (<0.001) residents with a higher education level (P=0.032) and were also diagnosed at earlier stage (<0.001) and lower grade (<0.001). Surgery remained the primary treatment method in all groups.

Conclusions: More studies on the commonality and heterogeneity of GEP-NENs are warranted to improve diagnosis efficiencies and treatment outcomes.
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http://dx.doi.org/10.18632/oncotarget.17599DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5641082PMC
September 2017

Association between oral leukoplakia and risk of upper gastrointestinal cancer death: A follow-up study of the Linxian General Population Trial.

Thorac Cancer 2017 11 20;8(6):642-648. Epub 2017 Sep 20.

Metabolic Epidemiology Branch, Division of Cancer Epidemiology & Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.

Background: This study was conducted to explore the association between oral leukoplakia (OL) and the risk of upper gastrointestinal cancer death in the Linxian General Population Trial Cohort.

Methods: A prospective cohort study of the Linxian General Population Trial Cohort was performed. Participants with OL were treated as an exposed group, and the remainder was selected as a control group. All subjects were followed monthly by village health workers and reviewed quarterly by the Linxian Cancer Registry. Hazard ratios (HRs) and 95% confidence interval (CIs) were evaluated using proportional hazard and proportional subdistribution hazard models, respectively.

Results: Over a median of 27 years of observation, 29 476 subjects were followed-up. A total of 17 473 deaths occurred, including 2345 esophageal squamous cell carcinoma (ESCC), 1139 gastric cardia carcinoma, and 506 gastric non-cardia carcinoma deaths. Significant increased ESCC mortality was observed in subjects with OL (exposed 9.66% vs. unexposed 7.39%; P < 0.0001). Furthermore, subjects with OL had a 22% higher risk of death from ESCC (HR 1.22, 95% CI 1.10-1.34; P = 0.0001) after adjusted covariates. In subjects aged ≤52 at the baseline, OL was significantly associated with an elevated risk of ESCC mortality (HR 1.32, 95% CI 1.13-1.54; P = 0.0005). No significant associations were observed for gastric cardia carcinoma and non-cardia carcinoma mortality.

Conclusions: OL may increase the risk of ESCC mortality, especially in the younger population. These associations should be investigated in further studies.
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http://dx.doi.org/10.1111/1759-7714.12501DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5707438PMC
November 2017

GWAS follow-up study of esophageal squamous cell carcinoma identifies potential genetic loci associated with family history of upper gastrointestinal cancer.

Sci Rep 2017 07 5;7(1):4642. Epub 2017 Jul 5.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institute of Health, Bethesda, MD, USA.

Based on our initial genome-wide association study (GWAS) on esophageal squamous cell carcinoma (ESCC) in Han Chinese, we conducted a follow-up study to examine the single nucleotide polymorphisms (SNPs) associated with family history (FH) of upper gastrointestinal cancer (UGI) cancer in cases with ESCC. We evaluated the association between SNPs and FH of UGI cancer among ESCC cases in a stage-1 case-only analysis of the National Cancer Institute (NCI, 541 cases with FH and 1399 without FH) and Henan GWAS (493 cases with FH and 869 without FH) data (discovery phase). The top SNPs (or their surrogates) from discovery were advanced to a stage-2 evaluation in additional Henan subjects (2801 cases with FH and 3136 without FH, replication phase). A total of 19 SNPs were associated with FH of UGI cancer in ESCC cases with P < 10 in the stage-1 meta-analysis of NCI and Henan GWAS data. In stage-2, the association for rs79747906 (located at 18p11.31, P = 5.79 × 10 in discovery) was replicated (P = 0.006), with a pooled-OR of 1.59 (95%CI: 1.11-2.28). We identified potential genetic variants associated with FH of UGI cancer. Our findings may provide important insights into new low-penetrance susceptibility regions involved in the susceptibility of families with multiple UGI cancer cases.
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http://dx.doi.org/10.1038/s41598-017-04822-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5498542PMC
July 2017

Body mass index and risk of gastric cancer: A 30-year follow-up study in the Linxian general population trial cohort.

Cancer Sci 2017 Aug 30;108(8):1667-1672. Epub 2017 Jun 30.

Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA.

Although a number of previous studies have noted either positive or no association for body mass index (BMI) and gastric cancer risk, little evidence exists in the Chinese population. We prospectively examined the associations of BMI with risk of gastric cancer in the Linxian General Population Trial cohort, with 29 584 healthy adults enrolled in 1985 and followed through to the end of 2014. Body weight and height were measured during physical examination at baseline and BMI was calculated as weight in kilograms divided by height in meters squared. Body mass index from 138 subjects was missing, and a total of 29 446 participants were included in the final analysis. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals. During 30 years of follow-up, we confirmed 1716 newly diagnosed gastric cardia adenocarcinoma (GCA) cases and 626 new gastric non-cardia adenocarcinoma (GNCA) cases. Overall, compared to the lowest quartile (BMI <20.32 kg/m ), subjects in the fourth quartile (BMI ≥23.31 kg/m ) subjects had lower risk of developing GNCA (hazard ratio, 0.65; 95% confidence interval, 0.51-0.83). Age- and sex-specific analyses showed that this protective effect was only observed in men and older (52 + years) persons. No associations were observed for BMI with GCA incidence. Higher BMI was associated with decreased risk of GNCA in this population, particularly in men and older persons. Future studies are needed to confirm these findings. The trial is registered with ClinicalTrials.gov: NCT00342654.
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http://dx.doi.org/10.1111/cas.13292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5543512PMC
August 2017

Epidemiology, etiology, and prevention of esophageal squamous cell carcinoma in China.

Cancer Biol Med 2017 Feb;14(1):33-41

Department of Cancer Epidemiology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.

Esophageal cancer is one of the most fatal diseases worldwide mainly because of its rapid progression and poor prognosis. Although the incidence of esophageal adenocarcinoma has markedly risen in North America and Europe in the past several decades, esophageal squamous cell carcinoma is still the predominant subtype of esophageal cancer, especially in China. It accounts for more than 90% of all esophageal squamous cell carcinoma cases in China. Geographical differentiation is one of the most distinctive characteristics of esophageal cancer. The progression, risk factors, and prognosis of these two subtypes of esophageal cancer differ. This study reviews the epidemiology, etiology, and prevention of esophageal squamous cell carcinoma in China, thereby providing systematic references for policy-makers who will decide on issues of esophageal cancer prevention and control.
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http://dx.doi.org/10.20892/j.issn.2095-3941.2016.0093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5365188PMC
February 2017

Influence of occupation and education level on breast cancer stage at diagnosis, and treatment options in China: A nationwide, multicenter 10-year epidemiological study.

Medicine (Baltimore) 2017 Apr;96(15):e6641

Department of Breast Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an Department of Cancer Epidemiology, Cancer Institute & Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Department of Epidemiology, West China School of Public Health, Sichuan University, Chengdu, Sichuan Department of Breast Surgery, Zhejiang Cancer Hospital, Hangzhou Department of Breast Oncology, Sun Yat-Sen University Cancer Center, Guangzhou Department of Breast-thyroid Surgery, Xiangya Second Hospital, Central South University, Changsha Department of Breast Surgery, Liaoning Cancer Hospital, Shenyang Center of Breast Disease, Cancer Institute & Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Department of Pathology, Cancer Institute & Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, P.R. China.

The objective of this study was to evaluate the impact of occupation and education level of Chinese female breast cancer patients on their cancer staging at diagnosis, clinical and pathological features, rate of implementation, and selection of treatment.The medical charts of 4211 confirmed female breast cancer cases diagnosed between 1999 and 2008, from 7 breast cancer centers spread across the whole of China, were reviewed. Data including information on the patient's sociodemographic status, clinical and pathological characteristics, implementation of clinical examination and treatment modalities were analyzed. In parallel, the associations between different occupations and level of educational attainment were analyzed in relation to tumor stage through TNM staging, clinical and pathological characteristics, implementation of clinical examination, and treatment patterns. Multivariate logistic regression was used to identify whether the occupation and education level of patients are independent factors of TNM staging at diagnosis.There were significant differences among different occupation groups and the education level of patients in regards to pathological characteristics and treatment choice. Both the occupation and education level of patients were independent factors of TNM staging at diagnosis. For patients within the lower-income occupation or lower educational attainment group, the tumor stage was later, the rates of implementation of relevant investigations were lower, as were the rates of radiotherapy, chemotherapy, and endocrine therapy.This study suggests that strategies should work toward developing more accurate and effective breast cancer prevention and treatment strategies aimed specifically at patients with lower educational attainment levels and at specific occupation groups.
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http://dx.doi.org/10.1097/MD.0000000000006641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5403113PMC
April 2017

A nomogram to predict the probability of axillary lymph node metastasis in female patients with breast cancer in China: A nationwide, multicenter, 10-year epidemiological study.

Oncotarget 2017 May;8(21):35311-35325

Department of Breast Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, P.R. China.

Axillary lymph node dissection (ALND) or sentinel lymph node biopsy (SLNB) alone may lead to postoperative complications. Among patients with positive ALN in the preoperative examination, approximately 40% patients do not have SLN metastasis. Herein, we aimed to develop a model to predict the probability of ALN metastasis as a preoperative tool to support clinical decision-making. We retrospectively analyzed the clinicopathological features of 4211 female patients with breast cancer who were diagnosed in seven breast cancer centers representing entire China, over 10 years (1999-2008). The patients were randomly categorized into a training cohort or validation cohort (3:1 ratio). Multivariate logistic regression analysis was performed for 1869 patients with complete information on the study variables. Age at diagnosis, tumor size, tumor quadrant, clinical nodal status, local invasion status, pathological type, and molecular subtypes were the independent predictors of ALN metastasis. The nomogram was then developed using the seven variables. Further, it was subsequently validated in 642 patients with complete data on variables in the validation cohort. Coefficient of determination (R²) and the area under the receiver-operating characteristic (ROC) curve (AUC) were calculated to be 0.979 and 0.7007, showing good calibration and discrimination of the model, respectively. The false-negative rates of the nomogram were 0 and 6.9% for the predicted risk cut-off values of 14.03% and 20%, respectively. Therefore, when the predicted risk is less than 20%, SLNB may be avoided. After further validation in various patient populations, this model may support increasingly limited axillary surgery in breast cancer.
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http://dx.doi.org/10.18632/oncotarget.13330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5471057PMC
May 2017

Optimal Cutoff Scores for Alzheimer's Disease Using the Chinese Version of Mini-Mental State Examination Among Chinese Population Living in Rural Areas.

Am J Alzheimers Dis Other Demen 2016 12 22;31(8):650-657. Epub 2016 Sep 22.

Department of Cancer Epidemiology, Cancer Hospital/Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.

To explore the optimal cutoff score for initial detection of Alzheimer's Disease (AD) through the Chinese version of Mini-Mental State Examination (CMMSE) in rural areas in China, we conducted a cross-sectional study within the Linxian General Population Nutritional Follow-up study. 16,488 eligible cohort members participated in the survey and 881 completed the CMMSE. Among 881 participants, the median age (Interquartile range) was 69.00 (10.00), 634 (71.92%) were female, 657 (74.57%) were illiterate, 35 (3.97%) had 6 years of education or higher, and 295 (33.48%) were diagnosed with AD. By reducing the CMMSE criteria for illiterate to 16 points, primary school to 19 points, and middle school or higher to 23 points, the efficiency of Chinese version of Mini-Mental State Examination can be significantly improved for initial detection of AD in rural areas in China, especially in those nutrition deficient areas.
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http://dx.doi.org/10.1177/1533317516662336DOI Listing
December 2016

Body mass index and long-term risk of death from esophageal squamous cell carcinoma in a Chinese population.

Thorac Cancer 2016 Jul 7;7(4):387-92. Epub 2016 Apr 7.

Division of Cancer Epidemiology and Genetics National Cancer Institute, National Institutes of Health Bethesda USA.

Background: Studies based on Western populations have found that body mass index (BMI) is positively related to the risk of esophageal adenocarcinoma but inversely associated with esophageal squamous cell carcinoma (ESCC). Little reliable evidence exists of an association between BMI and ESCCin China, where ESCC incidence is high but BMI is low.

Methods: We evaluated the BMI-ESCC association in a population-based prospective study of 29 446 Chinese aged 40-69 with 27 years of follow-up. China-specific BMI cut-offs (underweight < 18.5, healthy ≥ 18.5 to <24, overweight ≥ 24 to <28, and obese ≥ 28) and quartile categories were used to define BMI subgroups. Adjusted hazard ratios (HRs) and confidence intervals (CIs) for death from ESCC by BMI subgroups were calculated using Cox proportional hazards models.

Results: During a median follow-up duration of 21.2 years (555 439 person-years), 2436 ESCC deaths were identified. BMI was protective for death from ESCC with an HR of 0.97 (95% CI 0.95-0.99) for each unit increase in BMI. Relative to healthy weight, HRs for BMI were 1.21 (95% CI 1.02-1.43) for the underweight group and 0.87 (95% CI 0.78-0.98) for the overweight. Categorical quartile analyses found people with BMIs in the Q3 and Q4 groups had 16% and 13% reductions in the risk of ESCC, respectively. Gender-specific analyses found that clear effects were evident in women only.

Conclusions: Higher BMI was associated with a reduced risk of ESCC in aChinese population.
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http://dx.doi.org/10.1111/1759-7714.12340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4930956PMC
July 2016

Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome.

Nat Commun 2016 06 13;7:11843. Epub 2016 Jun 13.

National Institute of Cancer Research, National Health Research Institutes, Zhunan 35053, Taiwan.

To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events >2 Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases.
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http://dx.doi.org/10.1038/ncomms11843DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4909985PMC
June 2016

Dietary components and risk of total, cancer and cardiovascular disease mortality in the Linxian Nutrition Intervention Trials cohort in China.

Sci Rep 2016 Mar 4;6:22619. Epub 2016 Mar 4.

Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, 20850, USA.

Although previous studies have shown that dietary consumption of certain food groups is associated with a lower risk of cancer, heart disease and stroke mortality in western populations, limited prospective data are available from China. We prospectively examined the association between dietary intake of different food groups at baseline and risk of total, cancer, heart disease and stroke mortality outcomes in the Linxian Nutrition Intervention Trials(NIT) cohort. In 1984-1991, 2445 subjects aged 40-69 years from the Linxian NIT cohort completed a food frequency questionnaire. Deaths from esophageal and gastric cancer, heart disease and stroke were identified through up to 26 years of follow-up. We used Cox proportional hazard models to calculate hazard ratios and 95% confidence intervals for associations between intake of groups of food items and these mortality endpoints. We concluded that higher intake of certain food groups was associated with lower risk of gastric cancer, heart disease and stroke mortality in a prospective cohort in rural China. Our findings provide additional evidence that increasing intake of grains, vegetables, beans, fruits and nuts may help reduce mortality from these diseases.
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http://dx.doi.org/10.1038/srep22619DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4778051PMC
March 2016
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