Publications by authors named "Christian C Abnet"

325 Publications

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

Cigarette Smoking and Opium Use in Relation to the Oral Microbiota in Iran.

Microbiol Spectr 2021 Sep 15:e0013821. Epub 2021 Sep 15.

Metabolic Epidemiology Branch, Division of Cancer Epidemiology & Genetics, National Cancer Institutegrid.48336.3a, Bethesda, Maryland, USA.

Cigarettes and opium contain chemicals and particulate matter that may modify the oral microbiota. This study aimed to investigate the association between cigarette and opium use with the oral microbiota. A total of 558 participants were recruited from Iran between 2011 and 2015. Individuals were categorized as never cigarette nor opium users, ever cigarette-only smokers, ever opium-only users, and ever both cigarette and opium users. Participants provided saliva samples for 16S rRNA gene sequencing. Logistic regression, microbiome regression-based kernel association test (MiRKAT), and zero-inflated beta regression models were calculated. For every increase in 10 observed amplicon sequence variants (ASVs), the odds for being a cigarette-only smoker, opium-only user, and both user compared to never users decreased by 9% (odds ratio [OR] = 0.91; 95% confidence interval [95% CI] = 0.86 to 0.97), 13% (OR = 0.87; 95% CI = 0.75 to 1.01), and 12% (OR = 0.88; 95% CI = 0.80 to 0.96), respectively. The microbial communities differed by cigarette and opium use as indicated by MiRKAT models testing the three beta-diversity matrices ( < 0.05 for all). Three genera were less likely and one genus was more likely to be detected in cigarette-only smokers or opium-only users than in never users. The relative abundance of the phylum (never, 14.78%; both, 21.20%) was higher and the phyla (never, 17.63%; both, 11.62%) and (never, 9.06%; both, 3.70%) were lower in users of both cigarettes and opium, while the phylum (never, 54.29%; opium, 65.49%) was higher in opium-only users. Cigarette and opium use was associated with lower alpha-diversity, overall oral microbiota community composition, and both the presence and relative abundance of multiple taxa. Cigarette smoking and opium use are associated with periodontal disease caused by specific bacteria such as Porphyromonas gingivalis, which suggests a link between cigarette smoking and opium use and the oral microbiota. Alterations of the oral microbiota in cigarette smokers compared to nonsmokers have been reported, but this has not been studied across diverse populations. Additionally, the association of opium use with the oral microbiota has not been investigated to date. We conducted this study to investigate differences in the oral microbiota between ever users of cigarettes only, opium only, and both cigarettes and opium and never users of cigarettes and opium in Iran. Lower alpha-diversity, distinct overall oral microbial communities, and the presence and relative abundance of multiple taxa have been found for users of cigarettes and/or opium.
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http://dx.doi.org/10.1128/Spectrum.00138-21DOI Listing
September 2021

Microbiome and Cancers of the Esophagus: A Review.

Microorganisms 2021 Aug 18;9(8). Epub 2021 Aug 18.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Esophageal cancer (EC) is an aggressive malignant disease ranking amongst the leading causes of cancer deaths in the world. The two main histologic subtypes, esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), have distinct geographic and temporal patterns and risk factor profiles. Despite decades of research, the factors underlying these geo-temporal patterns are still not fully understood. The human microbiome has recently been implicated in various health conditions and disease, and it is possible that the microbiome may play an important role in the etiology of EC. Although studies of the microbiome and EC are still in their early stages, we review our current understanding of the potential links between ESCC, EAC, and bacterial communities in the oral cavity and esophagus. We also provide a summary of the epidemiology of EC and highlight some key challenges and future directions.
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http://dx.doi.org/10.3390/microorganisms9081764DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8398938PMC
August 2021

Dietary acid load and mortality from all causes, CVD and cancer: results from the Golestan Cohort Study.

Br J Nutr 2021 Aug 16:1-7. Epub 2021 Aug 16.

Department of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Given the limited studies and controversial results on association between dietary acid load and mortality from CVD and cancers, we aimed to investigate this association in a large population cohort study in Middle East, with a wide range of dietary acid load. The study was conducted on the platform of the Golestan Cohort Study (GCS), which enrolled 50 045 participants in 2004-2008. Dietary intake was assessed using a validated FFQ. Dietary potential renal acid load (PRAL) score was calculated from nutrient intake. Death and its causes were identified and confirmed by two or three physicians. Cox proportional hazards regression was used to estimate hazard ratio (HR) and 95 % CI for total and cause-specific mortalities. Then, the associations were modelled using restricted cubic splines. PRAL range was -57·36 to +53·81 mEq/d for men and -76·70 to +49·08 for women. During 555 142 person-years of follow-up, we documented 6830 deaths, including 3070 cardiovascular deaths, 1502 cancer deaths and 2258 deaths from other causes. For overall deaths, in final model after adjustment for confounders, participants in the first and fifth quintiles of PRAL had a higher risk of mortality compared with the second quintile of PRAL (HR: 1·08; 95 % CI1·01, 1·16 and HR: 1·07; 95 % CI 1·01, 1·15, respectively); Pfor trend < 0·05). Participants in the first and fifth quintiles of PRAL had a 12 % higher risk of CVD mortality compared with the Q2 of PRAL (HR: 1·12; 95 % CI 1·01-1·25 and HR: 1·12; 95 % CI 1·01, 1·26, respectively; Pfor trend < 0·05). We found that all-cause and CVD mortality rates were higher in the lowest and highest PRAL values, in an approximately U-shaped relation (P-values for the overall association and the non-linear association of energy-adjusted PRAL with total mortality were < 0·001 and < 0·001, and with CVD mortality were 0·008 and 0·003, respectively). Our results highlight unfavourable associations of high acidity and alkalinity of diet with the increased total and CVD mortality risk. It may be important to consider a balanced acid-base diet as a protective strategy to prevent pre-mature death, especially from CVD.
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http://dx.doi.org/10.1017/S0007114521003135DOI Listing
August 2021

Associations between Biomarkers of Exposure and Lung Cancer Risk among Exclusive Cigarette Smokers in the Golestan Cohort Study.

Int J Environ Res Public Health 2021 07 9;18(14). Epub 2021 Jul 9.

Center for Tobacco Products, Food and Drug Administration, Silver Spring, MD 20993, USA.

Biomarkers of tobacco exposure are known to be associated with disease risk but previous studies are limited in number and restricted to certain regions. We conducted a nested case-control study examining baseline levels and subsequent lung cancer incidence among current male exclusive cigarette smokers in the Golestan Cohort Study in Iran. We calculated geometric mean biomarker concentrations for 28 matched cases and 52 controls for the correlation of biomarker levels among controls and for adjusted odds' ratios (ORs) for lung cancer incidence by biomarker concentration, accounting for demographic characteristics, smoking quantity and duration, and opium use. Lung cancer cases had higher average levels of most biomarkers including total nicotine equivalents (TNE-2), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), and 3-hydroxyfluorene (3-FLU). Many biomarkers correlated highly with one another including TNE-2 with NNAL and N-Acetyl-S-(2-cyanoethyl)-L-cysteine (2CYEMA), and N-Acetyl-S-(4-hydroxy-2-buten-1-yl)-L-cysteine (t4HBEMA) with N-Acetyl-S-(3-hydroxypropyl-1-methyl)-L-cysteine (3HMPMA) and N-Acetyl-S-(4-hydroxy-2-methyl-2-buten-1-yl)-L-cysteine (4HMBEMA). Lung cancer risk increased with concentration for several biomarkers, including TNE-2 (OR = 2.22, 95% CI = 1.03, 4.78) and NNN (OR = 2.44, 95% CI = 1.13, 5.27), and estimates were significant after further adjustment for demographic and smoking characteristics for 2CYEMA (OR = 2.17, 95% CI = 1.03, 4.55), N-Acetyl-S-(2-carbamoylethyl)-L-cysteine (2CAEMA) (OR = 2.14, 95% CI = 1.01, 4.55), and N-Acetyl-S-(2-hydroxypropyl)-L-cysteine (2HPMA) (OR = 2.85, 95% CI = 1.04, 7.81). Estimates were not significant with adjustment for opium use. Concentrations of many biomarkers were higher at the baseline for participants who subsequently developed lung cancer than among the matched controls. Odds of lung cancer were higher for several biomarkers including with adjustment for smoking exposure for some but not with adjustment for opium use.
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http://dx.doi.org/10.3390/ijerph18147349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8306295PMC
July 2021

Population Attributable Risks of Subtypes of Esophageal and Gastric Cancers in the United States.

Am J Gastroenterol 2021 09;116(9):1844-1852

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

Introduction: To help target preventive strategies, we estimated US population attributable risks (PARs) of demographic and potentially modifiable risk factors for esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), gastric cardia adenocarcinoma (GCA), and gastric noncardia adenocarcinoma (GNCA).

Methods: We prospectively examined the associations for risk factors and these cancers in 490,605 people in the National Institutes of Health-the American Association of Retired Persons Diet and Health cohort Diet and Health Study cohort from 1995 to 2011. Exposures were obtained from the baseline questionnaire. Diagnoses of gastroesophageal reflux disease were extracted for a subset of eligible National Institutes of Health-the American Association of Retired Persons Diet and Health cohort subjects through linkage to Medicare and then multiply imputed for non-Medicare-eligible subjects. Hazard ratios were calculated using multivariable-adjusted Cox proportional hazards regression. Adjusted population attributable risks were calculated for the US population aged 50-71 years by combining the hazard ratios with the estimated joint distribution of risk factor prevalence from the 2015 National Health Interview Survey.

Results: Smoking remained the most important risk factor for ESCC and was estimated to cause more than 1/3 of EAC and GCA and 1/10 of GNCA. Obesity and gastroesophageal reflux disease were associated with more than 1/2 of EAC and 1/3 of GCA. Compared with each lowest-risk level category, common risk factors were estimated to be associated with 73.7% of ESCC (95% confidence interval [CI]: 62.1%-85.4%), 70.3% of EAC (95% CI: 64.4%-76.2%), 69.3% of GCA (95% CI: 61.0%-77.7%), and 33.6% of GNCA (95% CI: 21.7%-45.5%).

Discussion: These factors accounted for a large proportion of esophageal and gastric cancers in the United States, highlighting opportunities for education and intervention to reduce the burden of these highly fatal cancers.
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http://dx.doi.org/10.14309/ajg.0000000000001355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8410651PMC
September 2021

Association between serum ferritin, incident primary liver cancer, and chronic liver disease mortality in the Linxian Nutrition Intervention Trials: A nested case-control study.

J Gastroenterol Hepatol 2021 Jun 9. Epub 2021 Jun 9.

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

Background And Aim: Previous studies suggest that serum ferritin may be associated with higher risk of liver cancer. However, additional studies of the association are needed. It is also not clear whether serum ferritin is associated with mortality from chronic liver disease (CLD).

Methods: We performed a nested case-control study in the Linxian Nutrition Intervention Trials. Baseline serum ferritin was measured for 226 incident primary liver cancer cases, 281 CLD mortalities diagnosed, and 1061 age-matched, gender-matched, and trial-matched controls. We used multivariable logistic regression models to calculate odds ratios and 95% confidence intervals. Subgroup analysis and interaction tests were performed by age, gender, alcohol drinking, hepatitis B virus seropositivity (HBV+)/hepatitis C virus seropositivity (HCV+), and trial.

Results: Participants with serum ferritin in the highest quartile, as compared with those in the lowest quartile, had an increased risk of CLD mortality (odds ratio = 1.72, 95% confidence interval = 1.12, 2.64, P-trend < 0.01). Moreover, the association with higher serum ferritin was stronger among alcohol drinkers and those who were HCV+ (P-interaction < 0.05). For incident liver cancer, risk estimates were above one but were not statistically significant.

Conclusion: In this study, higher levels of serum ferritin at baseline were associated with subsequent mortality from CLD, particularly if combined with alcohol drinking or viral hepatitis. Further work is warranted to confirm our findings.
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http://dx.doi.org/10.1111/jgh.15571DOI Listing
June 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

Red Meat Consumption and Risk of Nonalcoholic Fatty Liver Disease in a Population With Low Meat Consumption: The Golestan Cohort Study.

Am J Gastroenterol 2021 08;116(8):1667-1675

Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran.

Introduction: Nonalcoholic fatty liver disease (NAFLD), as the most common liver disease in the world, can range from simple steatosis to steatohepatitis. We evaluated the association between meat consumption and risk of NAFLD in the Golestan Cohort Study (GCS).

Methods: The GCS enrolled 50,045 participants, aged 40-75 years in Iran. Dietary information was collected using a 116-item semiquantitative food frequency questionnaire at baseline (2004-2008). A random sample of 1,612 cohort members participated in a liver-focused study in 2011. NAFLD was ascertained through ultrasound. Total red meat consumption and total white meat consumption were categorized into quartiles based on the GCS population, with the first quartile as the referent group. Multivariable logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs).

Results: The median intake of total red meat was 17 and total white meat was 53 g/d. During follow-up, 505 individuals (37.7%) were diagnosed with NAFLD, and 124 of them (9.2%) had elevated alanine transaminase. High total red meat consumption (ORQ4 vs Q1 = 1.59, 95% CI = 1.06-2.38, P trend = 0.03) and organ meat consumption (ORQ4 vs Q1 = 1.70, 95% CI = 1.19-2.44, P trend = 0.003) were associated with NAFLD. Total white meat, chicken, or fish consumption did not show significant associations with NAFLD.

Discussion: In this population with low consumption of red meat, individuals in the highest group of red meat intake were at increased odds of NAFLD. Furthermore, this is the first study to show an association between organ meat consumption and NAFLD (see Visual Abstract, http://links.lww.com/AJG/B944).
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http://dx.doi.org/10.14309/ajg.0000000000001229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8460710PMC
August 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

Oral Health and Risk of Upper Gastrointestinal Cancers in a Large Prospective Study from a High-risk Region: Golestan Cohort Study.

Cancer Prev Res (Phila) 2021 Jul 17;14(7):709-718. Epub 2021 Mar 17.

Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, Maryland.

Tooth loss and periodontal disease have been associated with several cancers, and poor oral health may be an important risk factor for upper gastrointestinal (UGI, i.e., esophageal and gastric) cancers. We assessed the relationship between oral health and UGI cancers using a large prospective study of over 50,000 adults living in Golestan Province, Iran, a high-incidence area for these cancers. Hazard ratios (HRs) and 95% confidence intervals (CI) were estimated for the association between three different measures of oral health [frequency of tooth brushing; number of missing teeth; and the sum of decayed, missing, and filled teeth (DMFT)] and UGI cancers. During a median follow-up duration of 13 years, there were 794 incident UGI cancers (396 esophageal and 398 gastric cancers). Daily tooth brushing was associated with a decreased risk of developing both esophageal (HR = 0.670; 95% CI: 0.486-0.924) and gastric (HR = 0.741; 95% CI: 0.544-1.01) cancers (combined UGI cancer HR = 0.697; 95% CI: 0.558-0.871) compared with never brushing. Tooth loss in excess of the loess smoothed, age- and sex-specific median number of teeth lost was significantly associated with esophageal (HR = 1.64; 95% CI: 1.08-2.47) and gastric cancers (HR = 1.58; 95% CI: 1.05-2.38). There were some adverse associations between DMFT and UGI cancers but most were not statistically significant. These results suggest increased risk of developing UGI cancers among individuals with poor oral health, and those who do not perform regular oral hygiene. PREVENTION RELEVANCE: Poor oral health is associated with the risk of upper gastrointestinal cancers, and oral hygiene practices may help prevent these cancers.
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http://dx.doi.org/10.1158/1940-6207.CAPR-20-0577DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295188PMC
July 2021

Indoor wood combustion, carcinogenic exposure and esophageal cancer in southwest Kenya.

Environ Int 2021 07 6;152:106485. Epub 2021 Mar 6.

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

Background: Exposure to polycyclic aromatic hydrocarbons (PAHs) is a risk factor for esophageal squamous cell carcinoma (ESCC) in high-incidence areas of China, Iran and Brazil, but PAH assessments have not been conducted in East Africa, another ESCC hot spot.

Objective: To evaluate demographic or lifestyle factors associated with the PAH biomarker concentrations in the study population, and whether PAH metabolite concentrations showed any associations with esophageal precancerous lesions.

Methods: We recruited a community-based sample of 289 asymptomatic adults from a rural area of Kenya and performed Lugol's chromoendoscopy to detect esophageal squamous dysplasia (ESD); participants completed a questionnaire and provided a spot urine specimen. We analyzed urine for seven hydroxylated metabolites of naphthalene, fluorene, phenanthrene, and pyrene at the U.S. National Center for Environmental Health, and compared creatinine-corrected PAH metabolite concentrations with questionnaire data and the presence of ESD.

Results: PAH metabolite concentrations among never tobacco users in these rural Kenya residents were 2.4-28.1 times higher than those reported from never tobacco users in Iran, Brazil and the USA. Female sex, cooking indoors, having no post-primary education, and age <50, but not tobacco use, were positively and significantly associated with PAH metabolite concentrations. Almost all participants used wood as cooking fuel. Nine participants had advanced ESD. Adjusted logistic regression showed a significant association between 2-hydroxynaphthalene (OR = 4.19, 95%CI: 1.01-17.47) and advanced ESD. All other PAH metabolites had positive but non-significant associations with advanced ESD.

Conclusions: Urinary PAH metabolite concentrations among never tobacco users are markedly higher in this group from Kenya than in other populations and are associated with indoor cooking with wood on open, unvented stoves. These metabolite concentrations were also associated with the presence of advanced esophageal dysplasia. Our findings underline the importance of assessing alternative cooking conditions to reduce PAH exposure in this population.
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http://dx.doi.org/10.1016/j.envint.2021.106485DOI Listing
July 2021

Seroprevalence and Determinants of Helicobacter pylori Infection in the Hispanic Community Health Study/Study of Latinos.

Clin Gastroenterol Hepatol 2021 Mar 2. Epub 2021 Mar 2.

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

Background & Aims: Helicobacter pylori infection is the primary known risk factor for gastric cancer. Despite the global decline in H. pylori prevalence, this infection remains a major public health concern in developing areas, including Latin America. Our study aimed to determine H. pylori seroprevalence and identified its determinants among Hispanics/Latinos living in the United States (U.S.).

Methods: The Hispanic Community Health Study/Study of Latinos (HCHS/SOL) is a population-based sample of self-identified Hispanics/Latinos (n = 16,144) in four U.S. communities, aged 18 to 74 years, recruited from randomly selected households using a stratified two-stage area probability sample design based on sampling households within sampled census block groups weighted for differential response rates. Anti-H. pylori immunoglobulin G antibodies were measured by an enzyme-linked immunosorbent assay using plasma samples. We calculated adjusted seroprevalence (i.e., predicted margins) from multivariable logistic regression models.

Results: The overall weighted H. pylori seroprevalence was 57% among HCHS/SOL participants, with 38% and 62% seropositivity among U.S.-born and non-U.S.-born individuals, respectively. Age-adjusted prevalence varied by self-reported Hispanic/Latino background, ranging from 47% in Puerto Rican to 72% in Central American backgrounds. Adjusted H. pylori seroprevalence was higher in the following groups: older age, male sex, lower education, non-U.S. born status, smoking, greater number of missing teeth, fewer doctor visits, lower ferritin level, and hepatitis A seropositivity.

Conclusions: H. pylori seroprevalence in Hispanics/Latinos remains high and differed significantly by Hispanic/Latino background. H. pylori seropositivity is strongly associated with poor socioeconomic conditions. These findings highlight the ongoing importance of this bacterial infection in the U.S.
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http://dx.doi.org/10.1016/j.cgh.2021.02.042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8410907PMC
March 2021

Long-term opiate use and risk of cardiovascular mortality: results from the Golestan Cohort Study.

Eur J Prev Cardiol 2021 03;28(1):98-106

Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Shariati Hospital, North Kargar Avenue, Tehran 14117-13135, Iran.

Aims: Tens of millions of people worldwide use opiates but little is known about their potential role in causing cardiovascular diseases. We aimed to study the association of long-term opiate use with cardiovascular mortality and whether this association is independent of the known risk factors.

Methods And Results: In the population-based Golestan Cohort Study-50 045 Iranian participants, 40-75 years, 58% women-we used Cox regression to estimate hazard ratios and 95% confidence intervals (HRs, 95% CIs) for the association of opiate use (at least once a week for a period of 6 months) with cardiovascular mortality, adjusting for potential confounders-i.e. age, sex, education, wealth, residential place, marital status, ethnicity, and tobacco and alcohol use. To show independent association, the models were further adjusted for hypertension, diabetes, waist and hip circumferences, physical activity, fruit/vegetable intake, aspirin and statin use, and history of cardiovascular diseases and cancers. In total, 8487 participants (72.2% men) were opiate users for a median (IQR) of 10 (4-20) years. During 548 940 person-years-median of 11.3 years, >99% success follow-up-3079 cardiovascular deaths occurred, with substantially higher rates in opiate users than non-users (1005 vs. 478 deaths/100 000 person-years). Opiate use was associated with increased cardiovascular mortality, with adjusted HR (95% CI) of 1.63 (1.49-1.79). Overall 10.9% of cardiovascular deaths were attributable to opiate use. The association was independent of the traditional cardiovascular risk factors.

Conclusion: Long-term opiate use was associated with an increased cardiovascular mortality independent of the traditional risk factors. Further research, particularly on mechanisms of action, is recommended.
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http://dx.doi.org/10.1093/eurjpc/zwaa006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133380PMC
March 2021

Gastroesophageal reflux disease: A risk factor for laryngeal squamous cell carcinoma and esophageal squamous cell carcinoma in the NIH-AARP Diet and Health Study cohort.

Cancer 2021 Jun 22;127(11):1871-1879. Epub 2021 Feb 22.

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

Background: Prior studies have suggested that gastroesophageal reflux disease (GERD) may be associated with risk of squamous cancers of the larynx and esophagus; however, most of these studies have had methodological limitations or insufficient control for potential confounders.

Methods: We prospectively examined the association between GERD and esophageal adenocarcinoma (EADC), esophageal squamous cell carcinoma (ESCC), and laryngeal squamous cell carcinoma (LSCC) in 490,605 participants of the NIH-AARP Diet and Health Study cohort who were 50-71 years of age at baseline. Exposure to risk factors were obtained from the baseline questionnaire. GERD diagnosis was extracted among eligible participants via linkage to Medicare diagnoses codes and then multiply imputed for non-Medicare-eligible participants. Hazard ratios (HRs) and 95% CIs of GERD were computed using Cox regression.

Results: From 1995 to 2011, we accrued 931 cases of EADC, 876 cases of LSCC, and 301 cases of ESCC in this cohort and estimated multivariable-adjusted HRs of 2.23 (95% CI, 1.72-2.90), 1.91 (95% CI, 1.24-2.94), and 1.99 (95% CI, 1.39-2.84) for EADC, LSCC, and ESCC, respectively. The associations were independent of sex, smoking status, alcohol intake, and follow-up time periods. We estimated that among the general population in the United States, 22.04% of people aged 50-71 years suffered from GERD. Using risk factor distributions for the United States from national survey data, 16.92% of LSCC cases and 17.32% of ESCC cases among individuals aged 50-71 years were estimated to be associated with GERD.

Conclusion: GERD is a common gastrointestinal disorder, but future prospective studies are needed to replicate our findings. If replicated, they may inform clinical surveillance of GERD patients and suggest new avenues for prevention of these malignancies.
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http://dx.doi.org/10.1002/cncr.33427DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8406665PMC
June 2021

Dietary quality using four dietary indices and lung cancer risk: the Golestan Cohort Study (GCS).

Cancer Causes Control 2021 May 21;32(5):493-503. Epub 2021 Feb 21.

Stony Brook Cancer Center, New York, NY, USA.

Purpose: The lung cancer incidence in Iran has increased almost ten times over the past three decades. In addition to the known causes such as smoking and certain occupational exposure, dietary quality has been suggested to play a role in lung cancer. We aim to explore the association between dietary pattern and lung cancer risk among a Middle East population.

Methods: Data came from Golestan Cohort Study which included 48,421 participants with 136 lung cancer cases diagnosed during a median follow-up of 12 years. Multivariable Cox proportional hazards regression models were used to calculate the HRs and 95% CI of lung cancer risk by tertile of the four dietary index scores-the Health Eating Index (HEI)-2015, the Alternative Health Eating Index (AHEI)-2010, the Alternative Mediterranean Diet (AMED), and the Dietary Approach to Stop Hypertension (DASH)-Fung.

Results: A higher DASH-Fung score was inversely associated with risk of lung cancer after adjusting for potential confounders (tertile three vs. tertile one: HR = 0.59 (0.38-0.93); p for trend = 0.07), and p with smoking was 0.46. Similar findings were observed among current smokers with the HEI-2015 score (tertile three vs. tertile one: HR = 0.22 (0.08-0.60): p for trend < 0.01), and p between smoking and the HEI-2015 score was 0.03.

Conclusion: In the GCS, consuming a diet more closely aligned with the DASH diet was associated with a reduced risk of lung cancer, which appeared to be independent of smoking status. There was also an inverse link between the HEI-2015 score and lung cancer risk among current smokers. Our finding is particularly important for the Middle East population, as diet may play an important role in cancer prevention and overall health.
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http://dx.doi.org/10.1007/s10552-021-01400-wDOI Listing
May 2021

Circulating MicroRNAs in Relation to Esophageal Adenocarcinoma Diagnosis and Survival.

Dig Dis Sci 2021 Nov 6;66(11):3831-3841. Epub 2021 Jan 6.

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

Background And Aims: Tissue miRNA can discriminate between esophageal adenocarcinoma (EA) and normal epithelium. However, no studies have examined a comprehensive panel of circulating miRNAs in relation to EA diagnosis and survival.

Methods: We used all 62 EA cases from the US Multi-Center case-control study with available serum matched 1:1 to controls. Cases were followed for vital status. MiRNAs (n = 2064) were assessed using the HTG EdgeSeq miRNA Whole Transcriptome Assay. Differential expression analysis of miRNAs in relation to case-control status was conducted. In cases, Cox regression models were fit to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality. P values were adjusted using the Benjamini-Hochberg (BH) procedure for false discovery rate control. Predictive performance was assessed using cross-validation.

Results: Sixty-eight distinct miRNAs were significantly upregulated between cases and controls (e.g., miR-1255b-2-3p fold change = 1.74, BH-adjusted P = 0.01). Assessing the predictive performance of these significantly upregulated miRNAs yielded 60% sensitivity, 65% specificity, and 0.62 AUC. miR-4253 and miR-1238-5p were associated with risk of mortality after EA diagnosis (HR = 4.85, 95% CI: 2.30-10.23, BH-adjusted P = 0.04 and HR = 3.81, 95% CI: 2.02-7.19, BH-adjusted P = 0.04, respectively).

Conclusions: While they require replication, these findings suggest that circulating miRNAs may be associated with EA diagnosis and survival.
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http://dx.doi.org/10.1007/s10620-020-06740-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257775PMC
November 2021

Association Between Serological Responses to Two Zoonotic Ruminant Pathogens and Esophageal Squamous Cell Carcinoma.

Vector Borne Zoonotic Dis 2021 Feb 29;21(2):125-127. Epub 2020 Oct 29.

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

Questionnaire data have linked contact with ruminants to the risk of esophageal squamous cell carcinoma (ESCC) in high-risk Asian populations. To better understand this observed association, we investigated exposure to two major zoonotic ruminant pathogens relative to ESCC risk. Using enzyme-linked immunosorbent assay, immunofluorescence assay, and microagglutination test assays, we measured immunoglobulin G anti- and anti- spp. antibodies in patients with ESCC ( = 177) and population-based controls ( = 177) matched by age, gender, and residence area from the Golestan case-control study in Iran. We found a similarly high seroprevalence of in ESCC cases and controls (75% and 80%, respectively), and a similarly low seroprevalence of spp. (0% and 0.6%, respectively). While documenting a high exposure to one of two zoonotic ruminant infections, this exposure failed to explain the observed association of ruminant contact and ESCC risk in this high-risk population.
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http://dx.doi.org/10.1089/vbz.2020.2668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876355PMC
February 2021

Serum Metabolomics for Biomarker Screening of Esophageal Squamous Cell Carcinoma and Esophageal Squamous Dysplasia Using Gas Chromatography-Mass Spectrometry.

ACS Omega 2020 Oct 12;5(41):26402-26412. Epub 2020 Oct 12.

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, 17 South Panjiayuan Lane, Beijing 100021, China.

Background: Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies with poor diagnosis. Esophageal squamous dysplasia (ESD) is considered as an immediate precancerous lesion of ESCC. Lack of biomarkers for discriminating ESCC and ESD from healthy subjects limits the early diagnosis and treatment of ESCC. Therefore, a serum metabolomic strategy was conducted to identify and validate potential metabolic markers for the screening of ESCC and ESD subjects.

Methods: A total of 74 patients with ESCC, 72 patients with ESD, and 75 normal control (NC) subjects were enrolled in this study. Gas chromatography-mass spectrometry was used to acquire serum metabolic profiles. Pathway analysis was conducted to uncover the fluctuated metabolic pathways during ESCC. Multivariate analyses were used to screen and validate the biomarkers.

Results: ESCC, ESD, and NC subjects revealed progressively altered metabolic profiles, in which amino acids globally increased, while fatty acids decreased in ESCCs compared with the control groups. Pathway analysis demonstrated the activated biosynthesis of amino acids and inhibited desaturation of saturated fatty acids. The panel constructed with propanoic acid, linoleic acid, glycerol-3-phosphate, and l-glutamine showed the area under the curve (AUC), sensitivity, and specificity of 0.817, 0.75, and 0.74, respectively, in the discrimination of ESCC/ESD patients from NC subjects. The panel constructed by propanoic acid, l-leucine, and hydroxyproline revealed the AUC, sensitivity, and specificity of 0.819, 0.76, and 0.72, respectively, in the discrimination of ESD from NC subjects. The combination of hypoxanthine, 2-ketoisocaproic acid, l-glutamate, and l-aspartate showed the AUC, sensitivity, and specificity of 0.818, 0.83, and 0.74, respectively, in the discrimination of ESCC patients from ESD subjects.

Conclusions: Our study revealed the systematic landscape for metabolic alterations in sera of ESD and ESCC patients. The defined metabolite markers showed reasonable performance in the discrimination of ESCC and ESD patients, and may provide helpful reference for clinicians and biologists.
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http://dx.doi.org/10.1021/acsomega.0c02600DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7581083PMC
October 2020

Habitual dietary intake of flavonoids and all-cause and cause-specific mortality: Golestan cohort study.

Nutr J 2020 09 28;19(1):108. Epub 2020 Sep 28.

Digestive Oncology Research Center, Digestive Diseases Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.

Background And Objectives: Flavonoids are the most important group of polyphenols with well-known beneficial effects on health. However; the association of intake of total flavonoid or their subclasses with all-cause or cause-specific mortality is not fully understood. The present study aims to evaluate the association between intake of total flavonoid, flavonoid subclasses, and total and cause-specific mortality in a developing country.

Methods: A total number of 49,173 participants from the Golestan cohort study, who completed a validated food frequency questionnaire at recruitment, were followed from 2004 till 2018. Phenol-Explorer database was applied to estimate dietary intakes of total flavonoid and different flavonoid subclasses. Associations were examined using adjusted Cox proportional hazards models.

Results: During a mean follow-up of 10.63 years, 5104 deaths were reported. After adjusting for several potential confounders, the hazard ratios (HRs) of all-cause mortality for the highest versus the lowest quintile of dietary flavanones, flavones, isoflavonoids, and dihydrochalcones were 0.81 (95% confidence interval = 0.73-0.89), 0.83(0.76-0.92), 0.88(0.80-0.96) and 0.83(0.77-0.90), respectively. However, there was no association between total flavonoid intake or other flavonoid subclasses with all-cause mortality. In cause-specific mortality analyses, flavanones and flavones intakes were inversely associated with CVD mortality [HRs: 0.86(0.73-1.00) and 0.85(0.72-1.00)] and isoflavonoids and dihydrochalcones were the only flavonoid subclasses that showed a protective association against cancer mortality [HR: 0.82(0.68-0.98)].

Conclusion: The results of our study suggest that certain subclasses of flavonoids can reduce all-cause mortality and mortality rate from CVD and cancer.
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http://dx.doi.org/10.1186/s12937-020-00627-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523365PMC
September 2020

Methylated DNA Markers of Esophageal Squamous Cancer and Dysplasia: An International Study.

Cancer Epidemiol Biomarkers Prev 2020 12 18;29(12):2642-2650. Epub 2020 Sep 18.

Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.

Background: Discovery of methylated DNA markers (MDM) of esophageal squamous cell carcinoma (ESCC) has sparked interest in assessing these markers in tissue. We evaluated MDMs in ESCC from three geographically and ethnically distinct populations, and explored the feasibility of assaying MDMs from DNA obtained by swallowed balloon devices.

Methods: MDMs were assayed in ESCC and normal tissues obtained from the populations of United States, Iran, and China, and from exfoliative cytology specimens obtained by balloons in a Chinese population. Areas under the receiver operating curve (AUC) of MDMs discriminating ESCC from normal tissues were calculated. Random forest prediction models were built, trained on U.S. cases and controls, and calibrated to U.S.-only controls (model 1) and three-country controls (model 2). Statistical tests were used to assess the relationship between dysplasia and MDM levels in balloons.

Results: Extracted DNA from 333 ESCC and 322 normal tissues was analyzed, in addition to archival DNA from 98 balloons. For ESCC, model 1 validated in Iranian and Chinese tissues with AUCs of 0.90 and 0.87, and model 2 yielded AUCs of 0.99, 0.96, and 0.94 in tissues from the United States, Iran, and China, respectively. In Chinese balloons, MDMs showed a statistically significant trend of increasing levels with increasing grades of dysplasia ( < 0.004).

Conclusions: MDMs accurately discriminate ESCC from normal esophagus in tissues obtained from high- and low-incidence countries. Preliminary data suggest that levels of MDMs assayed in DNA from swallowed balloon devices increase with dysplasia grade. Larger studies are needed to validate these results.

Impact: MDMs coupled with minimally invasive collection methods have the potential for worldwide application in ESCC screening.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-0616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710574PMC
December 2020

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

Genetics and geography of leukocyte telomere length in sub-Saharan Africans.

Hum Mol Genet 2020 11;29(18):3014-3020

Department of Genetics, University of Pennsylvania, Philadelphia, PA, 19104, USA.

Leukocyte telomere length (LTL) might be causal in cardiovascular disease and major cancers. To elucidate the roles of genetics and geography in LTL variability across humans, we compared LTL measured in 1295 sub-Saharan Africans (SSAs) with 559 African-Americans (AAms) and 2464 European-Americans (EAms). LTL differed significantly across SSAs (P = 0.003), with the San from Botswana (with the oldest genomic ancestry) having the longest LTL and populations from Ethiopia having the shortest LTL. SSAs had significantly longer LTL than AAms [P = 6.5(e-16)] whose LTL was significantly longer than EAms [P = 2.5(e-7)]. Genetic variation in SSAs explained 52% of LTL variance versus 27% in AAms and 34% in EAms. Adjustment for genetic variation removed the LTL differences among SSAs. LTL genetic variation among SSAs, with the longest LTL in the San, supports the hypothesis that longer LTL was ancestral in humans. Identifying factors driving LTL variation in Africa may have important ramifications for LTL-associated diseases.
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http://dx.doi.org/10.1093/hmg/ddaa187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7645709PMC
November 2020

Joint effect of diabetes and opiate use on all-cause and cause-specific mortality: the Golestan cohort study.

Int J Epidemiol 2021 03;50(1):314-324

Digestive Oncology Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran.

Background: Many diabetic individuals use prescription and non-prescription opioids and opiates. We aimed to investigate the joint effect of diabetes and opiate use on all-cause and cause-specific mortality.

Methods: Golestan Cohort study is a prospective population-based study in Iran. A total of 50 045 people-aged 40-75, 28 811 women, 8487 opiate users, 3548 diabetic patients-were followed during a median of 11.1 years, with over 99% success follow-up. Hazard ratio and 95% confidence intervals (HRs, 95% CIs), and preventable death attributable to each risk factor, were calculated.

Results: After 533 309 person-years, 7060 deaths occurred: 4178 (10.8%) of non-diabetic non-opiate users, 757 (25.3%) diabetic non-users, 1906 (24.0%) non-diabetic opiate users and 219 (39.8%) diabetic opiate users. Compared with non-diabetic non-users, HRs (95% CIs) for all-cause mortality were 2.17 (2.00-2.35) in diabetic non-opiate users, 1.63 (1.53-1.74) in non-diabetic opiate users and 2.76 (2.40-3.17) in diabetic opiate users. Among those who both had diabetes and used opiates, 63.8% (95% CI: 58.3%-68.5%) of all deaths were attributable to these risk factors, compared with 53.9% (95% CI: 50%-57.4%) in people who only had diabetes and 38.7% (95% CI: 34.6%-42.5%) in non-diabetic opiate users. Diabetes was more strongly associated with cardiovascular than cancer mortality. The risk of early mortality in known cases of diabetes did not depend on whether they started opiate use before or after their diagnosis.

Conclusions: Using opiates is detrimental to the health of diabetic patients. Public awareness about the health effects of opiates, and improvement of diabetes care especially among individuals with or at risk of opiate use, are necessary.
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http://dx.doi.org/10.1093/ije/dyaa126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938504PMC
March 2021

Comparison of Oral Microbiota Collected Using Multiple Methods and Recommendations for New Epidemiologic Studies.

mSystems 2020 Jul 7;5(4). Epub 2020 Jul 7.

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

Epidemiologic studies use various biosample collection methods to study associations between human oral microbiota and health outcomes. However, the agreement between the different methods is unclear. We compared a commercially available OMNIgene ORAL kit to three alternative collection methods: Saccomanno's fixative, Scope mouthwash, and nonethanol mouthwash. Oral samples were collected from 40 individuals over 4 visits. Two samples were collected from each subject per visit: one with OMNIgene and one with an alternative method. DNA was extracted using the DSP DNA Virus Pathogen kit, and the V4 region of the 16S rRNA gene was PCR amplified and sequenced using MiSeq. Oral collection methods were compared based on alpha and beta diversity metrics and phylum- and genus-level relative abundances. All alpha diversity metrics were significantly lower for Saccomanno's fixative than for OMNIgene ( < 0.001), whereas the two mouthwashes were more similar to OMNIgene. Principal-coordinate analysis (PCoA) using the Bray-Curtis and weighted UniFrac beta diversity matrices showed large differences in the microbial compositions of samples collected with Saccomanno's compared to those with OMNIgene and the mouthwashes. Clustering by collection method was not observed in unweighted UniFrac PCoA plots, suggesting differences in relative abundances but not specific taxa detected by the collection methods. Relative abundances of most taxa were significantly different between OMNIgene and the other methods at each taxonomic level, with Saccomanno's showing the least agreement with OMNIgene. There were clear differences in oral microbial communities between the four oral collection methods, particularly for Saccomanno's fixative. We compared four different oral collection methods for studying the human oral microbiome: an OMNIgene ORAL kit, Scope mouthwash, nonethanol mouthwash, and Saccomanno's fixative. Our study shows that the type of the collection method can have a large impact on the results of an oral microbiome analysis. We recommend that one consistent oral collection method should be used for all oral microbiome comparisons. While Scope and nonethanol mouthwashes are less expensive and provide results similar to those with OMNIgene, Saccomanno's fixative may be unfavorable due to the microbial differences detected in this study. Our results will help guide the design of future oral microbiome studies.
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http://dx.doi.org/10.1128/mSystems.00156-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7343307PMC
July 2020

Esophageal Histological Precursor Lesions and Subsequent 8.5-Year Cancer Risk in a Population-Based Prospective Study in China.

Am J Gastroenterol 2020 07;115(7):1036-1044

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.

Introduction: Data on the associations between esophageal histological lesions and risk of esophageal squamous cell carcinoma (ESCC) in general populations are limited. We aimed to investigate these associations in a large Chinese general population to inform future Chinese ESCC screening guidelines.

Methods: We performed endoscopic screening of 21,111 participants aged 40-69 years from 3 high-risk areas of China in 2005-2009, and followed the cohort through 2016. Cumulative incidence and mortality rates of ESCC were calculated by baseline histological diagnosis, and hazard ratios of ESCC, overall and by age and sex, were assessed using the Cox proportional hazards models.

Results: We identified 143 new ESCC cases (0.68%) and 62 ESCC deaths (0.29%) during a median follow-up of 8.5 years. Increasing grades of squamous dysplasia were associated with the increasing risk of ESCC incidence and mortality. The cumulative ESCC incidence rates for severe dysplasia/carcinoma in situ, moderate dysplasia (MD), and mild dysplasia were 15.5%, 4.5%, and 1.4%, respectively. Older individuals (50-69 years) had 3.1 times higher ESCC incidence than younger individuals (40-49 years), and men had 2.4 times higher ESCC incidence than women.

Discussion: This study confirmed that increasing grades of squamous dysplasia are associated with increasing risk of ESCC and that severe dysplasia and carcinoma in situ require clinical treatment. This study suggests that in high-risk areas of China, patients with endoscopically worrisome MD should also receive therapy, the first screening can be postponed to 50 years, and endoscopic surveillance intervals for unremarkable MD and mild dysplasia can be lengthened to 3 and 5 years, respectively.
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http://dx.doi.org/10.14309/ajg.0000000000000640DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7477846PMC
July 2020

Household Fuel Use and the Risk of Gastrointestinal Cancers: The Golestan Cohort Study.

Environ Health Perspect 2020 06 17;128(6):67002. Epub 2020 Jun 17.

Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran.

Background: Three billion people burn nonclean fuels for household purposes. Limited evidence suggests a link between household fuel use and gastrointestinal (GI) cancers.

Objectives: We investigated the relationship between indoor burning of biomass, kerosene, and natural gas with the subsequent risk of GI cancers.

Methods: During the period 2004-2008, a total of 50,045 Iranian individuals 40-75 years of age were recruited to this prospective population-based cohort. Upon enrollment, validated data were collected on demographics, lifestyle, and exposures, including detailed data on lifetime household use of different fuels and stoves. The participants were followed through August 2018 with loss.

Results: During the follow-up, 962 participants developed GI cancers. In comparison with using predominantly gas in the recent 20-y period, using predominantly biomass was associated with higher risks of esophageal [hazard ratio (HR): 1.89; 95% confidence interval (CI): 1.02, 3.50], and gastric HR: 1.83; 95% CI: 1.01, 3.31) cancers, whereas using predominantly kerosene was associated with higher risk of esophageal cancer (HR: 1.84; 95% CI: 1.10, 3.10). Lifetime duration of biomass burning for both cooking and house heating (exclusive biomass usage) using heating-stoves without chimney was associated with higher risk of GI cancers combined (10-y HR: 1.14; 95% CI: 1.07, 1.21), esophageal (10-y HR: 1.19; 95% CI: 1.08, 1.30), gastric (10-y HR: 1.11; 95% CI: 1.00, 1.23), and colon (10-y HR: 1.26; 95% CI: 1.03, 1.54) cancers. The risks of GI cancers combined, esophageal cancer, and gastric cancer were lower when biomass was burned using chimney-equipped heating-stoves (strata difference , 0.003, and 0.094, respectively). Duration of exclusive kerosene burning using heating-stoves without chimney was associated with higher risk of GI cancers combined (10-y HR: 1.05; 95% CI: 1.00, 1.11), and esophageal cancer (10-y HR: 1.14; 95% CI: 1.04, 1.26).

Discussion: Household burning of biomass or kerosene, especially without a chimney, was associated with higher risk of some digestive cancers. Using chimney-equipped stoves and replacing these fuels with natural gas may be useful interventions to reduce the burden of GI cancers worldwide. https://doi.org/10.1289/EHP5907.
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http://dx.doi.org/10.1289/EHP5907DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299082PMC
June 2020

Opium use and subsequent incidence of cancer: results from the Golestan Cohort Study.

Lancet Glob Health 2020 05;8(5):e649-e660

Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran; Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran; Digestive Disease Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Background: Evidence is emerging for a role of opiates in various cancers. In this study, we aimed to investigate the association between regular opium use and cancer incidence.

Methods: This study was done in a population-based cohort of 50 045 individuals aged 40-75 years from northeast Iran. Data on participant demographics, diet, lifestyle, opium use, and different exposures were collected upon enrolment using validated questionnaires. We used proportional hazards regression models to estimate hazard ratios (HRs) and corresponding 95% CIs for the association between opium use and different cancer types.

Findings: During a median 10 years of follow-up, 1833 participants were diagnosed with cancer. Use of opium was associated with an increased risk of developing all cancers combined (HR 1·40, 95% CI 1·24-1·58), gastrointestinal cancers (1·31, 1·11-1·55), and respiratory cancers (2·28, 1·58-3·30) in a dose-dependent manner (p<0·001). For site-specific cancers, use of opium was associated with an increased risk of developing oesophageal (1·38, 1·06-1·80), gastric (1·36, 1·03-1·79), lung (2·21, 1·44-3·39), bladder (2·86, 1·47-5·55), and laryngeal (2·53, 1·21-5·29) cancers in a dose-dependent manner (p<0·05). Only high-dose opium use was associated with pancreatic cancer (2·66, 1·23-5·74). Ingestion of opium (but not smoking opium) was associated with brain (2·15, 1·00-4·63) and liver (2·46, 1·23-4·95) cancers in a dose-dependent manner (p<0·01). We observed consistent associations among ever and never tobacco users, men and women, and individuals with lower and higher socioeconomic status.

Interpretation: Opium users have a significantly higher risk of developing cancers in different organs of the respiratory, digestive, and urinary systems and the CNS. The results of this analysis show that regular use of opiates might increase the risk of a range of cancer types.

Funding: World Cancer Research Fund International, Cancer Research UK, Tehran University of Medical Sciences, US National Cancer Institute, International Agency for Research on Cancer.
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http://dx.doi.org/10.1016/S2214-109X(20)30059-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7196888PMC
May 2020
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