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Background: Helicobacter species (spp.) have been detected in human bile and hepatobiliary tissue Helicobacter spp. promote gallstone formation and hepatobiliary tumors in laboratory studies, though it remains unclear whether Helicobacter spp. contribute to these cancers in humans. We used a multiplex panel to assess whether seropositivity to Helicobacter (H.) hepaticus or H. bilis proteins was associated with the development of hepatobiliary cancers in the Finnish Alpha‐Tocopherol, Beta‐Carotene Cancer Prevention (ATBC) Study, and US‐based Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO). Methods: We included 62 biliary and 121 liver cancers, and 190 age‐matched controls from ATBC and 74 biliary and 105 liver cancers, and 364 age‐ and sex‐matched controls from PLCO. Seropositivity to 14 H. hepaticus and H. bilis antigens was measured using a multiplex assay. Odds ratios (ORs) and 95% confidence intervals (CIs) were adjusted for major hepatobiliary cancer risk factors and Helicobacter pylori serostatus. Results: Seropositivity to the H. bilis antigen, P167D, was associated with more than a twofold higher risk of liver cancer (OR: 2.38; 95% CI: 1.06, 5.36) and seropositivity to the H. hepaticus antigens HH0407 or HH1201, or H. bilis antigen, HRAG 01470 were associated with higher risk of biliary cancer (OR: 5.01; 95% CI: 1.53, 16.40; OR: 2.40; 95% CI: 1.00, 5.76; OR: 3.27; 95% CI: 1.14, 9.34, respectively) within PLCO. No associations for any of the H. hepaticus or H. bilis antigens were noted for liver or biliary cancers within ATBC. Conclusions: Further investigations in cohort studies should examine the role of Helicobacter spp. in the etiology of liver and biliary cancers. [ABSTRACT FROM AUTHOR]

Background: To evaluate the associations between pre-diagnostic levels of serum insulin, glucose and insulin resistance (HOMA-IR) and future risk of incident primary liver cancer (PLC) or chronic liver disease (CLD)-related mortality. Methods: We used a nested case-control design to evaluate subjects over 22 years of follow-up. Glucose, insulin, and three markers of hepatitis B virus (HBV) and hepatitis C virus were measured in fasting baseline serum from 119 incident PLCs, 157 CLD-death cases and 512 matched controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression to estimate the associations between insulin, glucose, HOMA-IR and the risk of PLC or CLD death. Results: Compared with the lowest quartile of insulin, multivariable adjusted models showed that subjects in the highest quartile had elevated odds of developing PLC (ORQ4/Q1 = 2.42, 95% CI = 1.26–4.75, Ptrend = 0.007), particularly in HBV-positive subjects (Pinteraction = 0.040), and of CLD death (ORQ4/Q1 = 1.80, 95% CI = 1.02–3.21, Ptrend = 0.018). For glucose, in the HBV-positive group, subjects in the fourth quartile had an increased risk of PLC (ORQ4/Q1 = 2.18, 95% CI = 1.07–4.60, Ptrend = 0.009), and of CLD mortality (ORQ4/Q1 = 1.75, 95% CI = 0.95–3.28, Ptrend = 0.019). Subjects with the highest HOMA-IR values had a threefold risk of developing PLC (ORQ4/Q1 = 2.94, 95% CI = 1.54–5.87, Ptrend = 0.001), and a twofold risk of CLD death (ORQ4/Q1 = 2.20, 95% CI = 1.25–3.94, Ptrend = 0.005). Conclusions: We found that serum insulin and HOMA-IR could potentially be risk factors for PLC or CLD death. [ABSTRACT FROM AUTHOR]

Background: Increasing proportions of smokers in Japan smoke <10 cigarettes per day (CPD). Yet, the health risks of low-intensity smoking in Asia are poorly understood.Methods: We performed a pooled analysis of 410 294 adults from nine population-based prospective cohort studies participating in the Japan Cohort Consortium. Cigarette-use data were collected at each study baseline in 1983-1994. Study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and cause-specific mortality were calculated using multivariable-adjusted Cox regression by CPD among current smokers and by age at cessation among former smokers, with never smokers as the referent group. Pooled HRs and CIs were computed using a random-effect model.Results: The smoking prevalence was 54.5% in men and 7.4% in women. About 15.5% of male and 50.4% of female current smokers smoked 1-10 CPD (low-intensity). Both male and female low-intensity smokers had higher all-cause mortality risks than never smokers. Risks were further higher with increasing CPD in a dose-response manner. HRs (95% CIs) were 1.27 (0.97-1.66), 1.45 (1.33-1.59) and 1.49 (1.38-1.62) for 1-2, 3-5 and 6-10 CPD, respectively, in men; 1.28 (1.01-1.62), 1.49 (1.34-1.66) and 1.68 (1.55-1.81) for 1-2, 3-5 and 6-10 CPD, respectively, in women. Similar associations were observed for smoking-related causes of death. Among former low-intensity smokers, younger age at cessation was associated with lower mortality risk.Conclusions: Smoking very low amounts was associated with increased mortality risks in Japan. All smokers should quit, even if they smoke very few CPD. [ABSTRACT FROM AUTHOR]

The article discusses a review by L. King and colleagues, published in the issue, which summarizes literature on polycyclic aromatic hydrocarbons (PAHs) in alcohol that suggests these chemicals could also play a role in alcohol-induced carcinogensis. Topics include factors that could advance understanding of the roles of specific PAHs and PAH mixtures and questions of interest for public health raised by the presence of known carcinogens in commonly consumed alcoholic beverages.

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. In a prospective cohort of 490,605 patients who were followed for 16 years, patients with a history of gastroesophageal reflux disease (GERD) have a 2‐fold higher risk of laryngeal squamous cell carcinoma and esophageal squamous cell carcinoma. Moreover, an estimated 17% of these cancer cases were associated with GERD. If replicated by future prospective studies, it may inform clinical surveillance of GERD patients and provide new avenues for prevention of these malignancies. [ABSTRACT FROM AUTHOR]

Despite decades of declining mortality rates, lung cancer remains the leading cause of cancer death in the United States. This article examines lung cancer incidence, stage at diagnosis, survival, and mortality using population‐based data from the National Cancer Institute, the Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries. Over the past 5 years, declines in lung cancer mortality became considerably greater than declines in incidence among men (5.0% vs. 2.6% annually) and women (4.3% vs. 1.1% annually), reflecting absolute gains in 2‐year relative survival of 1.4% annually. Improved outcomes likely reflect advances in treatment, increased access to care through the Patient Protection and Affordable Care Act, and earlier stage diagnosis; for example, compared with a 4.6% annual decrease for distant‐stage disease incidence during 2013–2019, the rate for localized‐stage disease rose by 3.6% annually. Localized disease incidence increased more steeply in states with the highest lung cancer screening prevalence (by 3%–5% annually) than in those with the lowest (by 1%–2% annually). Despite progress, disparities remain. For example, Native Americans have the highest incidence and the slowest decline (less than 1% annually among men and stagnant rates among women) of any group. In addition, mortality rates in Mississippi and Kentucky are two to three times higher than in most western states, largely because of elevated historic smoking prevalence that remains. Racial and geographic inequalities highlight longstanding opportunities for more concerted tobacco‐control efforts targeted at high‐risk populations, including improved access to smoking‐cessation treatments and lung cancer screening, as well as state‐of‐the‐art treatment. Recent declines in lung cancer mortality have outpaced those for incidence, reflecting gains in relative survival that are partly due to recent shifts to earlier stage at diagnosis. Persistent racial and geographic disparities reflect longstanding opportunities for public health intervention to reduce smoking and improve health care access. [ABSTRACT FROM AUTHOR]

Background: Coffee consumption has been associated with reduced risk for death in prospective cohort studies; however, data in nonwhites are sparse.Objective: To examine the association of coffee consumption with risk for total and cause-specific death.Design: The MEC (Multiethnic Cohort), a prospective population-based cohort study established between 1993 and 1996.Setting: Hawaii and Los Angeles, California.Participants: 185 855 African Americans, Native Hawaiians, Japanese Americans, Latinos, and whites aged 45 to 75 years at recruitment.Measurements: Outcomes were total and cause-specific mortality between 1993 and 2012. Coffee intake was assessed at baseline by means of a validated food-frequency questionnaire.Results: 58 397 participants died during 3 195 484 person-years of follow-up (average follow-up, 16.2 years). Compared with drinking no coffee, coffee consumption was associated with lower total mortality after adjustment for smoking and other potential confounders (1 cup per day: hazard ratio [HR], 0.88 [95% CI, 0.85 to 0.91]; 2 to 3 cups per day: HR, 0.82 [CI, 0.79 to 0.86]; ≥4 cups per day: HR, 0.82 [CI, 0.78 to 0.87]; P for trend < 0.001). Trends were similar between caffeinated and decaffeinated coffee. Significant inverse associations were observed in 4 ethnic groups; the association in Native Hawaiians did not reach statistical significance. Inverse associations were also seen in never-smokers, younger participants (<55 years), and those who had not previously reported a chronic disease. Among examined end points, inverse associations were observed for deaths due to heart disease, cancer, respiratory disease, stroke, diabetes, and kidney disease.Limitation: Unmeasured confounding and measurement error, although sensitivity analysis suggested that neither was likely to affect results.Conclusion: Higher consumption of coffee was associated with lower risk for death in African Americans, Japanese Americans, Latinos, and whites.Primary Funding Source: National Cancer Institute. [ABSTRACT FROM AUTHOR]

Background: Despite widespread popularity and possible health effects, the prevalence and distribution of coffee consumption in US adults are poorly characterized.Objective: We sought to estimate usual daily coffee intakes from all coffee-containing beverages, including decaffeinated and regular coffee, among US adults according to demographic, socioeconomic, and health-related factors.Methods: Dietary intake data from ≤2 nonconsecutive 24-h dietary recalls and a food-frequency questionnaire administered during the NHANES 2003-2006 were used to estimate the person-specific probability of consuming coffee on a particular day and the usual amount consumed on consumption days. Trends in population mean coffee consumption over time were evaluated by using multiple linear regression and 1-d 24-h recall data from NHANES 2003-2012. Analyses were weighted to be representative of the US adult population aged ≥20 y.Results: An estimated 154 million adults, or 75% of the US population, aged ≥20 y reported drinking coffee; 49% reported drinking coffee daily. Prevalence did not vary by sex, education, income, or self-reported general health (all P ≥ 0.05) but did vary by age, race/ethnicity, smoking status, and alcohol drinking (all P < 0.05). Among coffee drinkers, the mean ± SE usual intake was 14.1 ± 0.5 fluid ounces/d (417 ± 15 mL/d). Mean usual intakes were higher in men than women, in older age groups than in those aged 20 to <30 y, in non-Hispanic whites than in non-Hispanic blacks or Hispanic/other races, in smokers than in never smokers, and in daily alcohol consumers than in nonconsumers (all P < 0.05). Population mean coffee consumption was stable from 2003 to 2012 (P-trend = 0.09).Conclusions: Coffee is widely consumed in the United States, with usual intakes varying by lifestyle and demographic factors, most notably by age. Longitudinal studies are needed to determine whether observed differences by age reflect birth cohort effects or changes in drinking patterns over the lifetime. [ABSTRACT FROM AUTHOR]

Background: Coffee drinkers had a higher risk of lung cancer in some previous studies, but as heavy coffee drinkers tend to also be cigarette smokers, such findings could be confounded. Therefore, we examined this association in the nearly half a million participants of the US NIH-AARP Diet and Health Study.Methods: Typical coffee intake and smoking history were queried at baseline. During 4 155 256 person-years of follow-up, more than 9000 incident lung cancer cases occurred. We used Cox proportional hazards regression to estimate hazard ratios (HRs)and 95% confidence intervals for coffee intake and subsequent incidence of lung cancer. We also comprehensively adjusted for tobacco smoking and examined associations by detailed strata of tobacco use.Results: Coffee drinkers were far more likely to smoke than non-drinkers. Although coffee drinking was associated with lung cancer in age- and sex- adjusted models (HR for ≥ 6 cups/day compared with none: 4.56, 4.08-5.10), this association was substantially attenuated after adjusting for smoking (HR: 1.27, 1.14-1.42). Similar findings were observed for each different histological type of lung cancer, and for participants drinking predominantly caffeinated or decaffeinated coffee. Little evidence for an association was observed in our stratified analyses, either within never smokers or in most categories of tobacco use.Conclusions: Coffee drinking was positively associated with lung cancer in our study, although the association was substantially attenuated after adjustment for tobacco smoking. As our adjustment for lifetime tobacco use was imperfect, it is likely that the remaining association is due to residual confounding by smoking, although other explanations are possible. [ABSTRACT FROM AUTHOR]

Background: Historically, US women started smoking at a later age than men and had lower relative risks for smoking-related cancers. However, more recent birth cohorts of women and men have similar smoking histories and have now reached the high-risk age for cancer. The impact of these changes on cancer incidence has not been systematically examined.Methods: Relative risks (RR), 95% confidence intervals (CI) and attributable fractions were calculated for cigarette smoking and incidence of 20 smoking-related cancers in 186 057 women and 266 074 men of the National Institutes of Health-AARP cohort, aged 50 to 71 years in 1995 and followed for 11 years.Results: In the cohort, which included participants born between 1924 and 1945, most women and men started smoking as teenagers. RRs for current vs never smoking were similar in women and men for the following cancers: lung squamous-cell (RR women: 121.4, 95% CI: 57.3-257.4; RR men:114.6, 95% CI: 61.2-214.4), lung adenocarcinoma (RR women: 11.7, 95% CI: 9.8-14.0; RR men: 15.6, 95% CI: 12.5-19.6), laryngeal (RR women: 37.0, 95% CI: 14.9-92.3; RR men: 13.8, 95% CI: 9.3-20.2), oral cavity-pharyngeal (RR women:4.4, 95% CI: 3.3-6.0; RR men: 3.8, 95% CI: 3.0-4.7), oesophageal squamous cell (RR women: 7.3, 95% CI: 3.5-15.5; RR men: 6.2, 95% CI: 2.8-13.7), bladder (RR women: 4.7, 95% CI: 3.7-5.8; RR men: 4.0, 95% CI: 3.5-4.5), colon (RR women: 1.3, 95% CI: 1.2-1.5; RR men: 1.3, 95% CI: 1.1-1.4), and at other sites, with similar attributable fractions.Conclusions: RRs for current smoking and incidence of many smoking-related cancers are now similar in US women and men, likely reflecting converging smoking patterns. [ABSTRACT FROM AUTHOR]

Objective: Obesity and diabetes have been associated with liver cancer. However, recent US-based studies have suggested a lack of association between obesity and liver cancer among blacks and women.Methods: We conducted a nested case-control study within the Multiphasic Health Checkup (MHC) cohort of Kaiser Permanente Northern California (KPNC) members. Liver cancer was diagnosed using the KPNC Cancer Registry. Detailed self-administered questionnaires and a standardized examination that included measurement of height and weight and a 1-h glucose tolerance test were completed prior to diagnosis of liver cancer for cases (n=450) and matched controls (4489). Height and weight were utilized to calculate BMI (kg/m(2)) as a measure of adiposity: underweight (15-≤8.5kg/m(2)), normal weight (18.5-≤25kg/m(2)), overweight (25-≤30kg/m(2)), and obese (≥30kg/m(2)). Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI) for the association between BMI, diabetes, and serum glucose with subsequent incidence of liver cancer, in models that were stratified by birth cohort, race/ethnicity, and sex.Results: Compared to normal weight individuals, obese individuals had a 2.4-fold increased risk of liver cancer (OR=2.38, 95% CI: 1.68-3.36), and overweight individuals had a 32% increased risk (OR=1.32, 95% CI: 1.03-1.70). This association did not differ when stratified by birth cohort, race/ethnicity, or sex (pint>0.05). Among blacks and women, obesity was associated with at least a 2-fold increased risk of liver cancer (OR=2.29, 95% CI: 1.22-4.28 and OR=2.00, 95% CI: 1.14-3.52, respectively). More moderate increased odds ratios were noted for diabetes (OR=1.28, 95% CI: 0.65-2.54) and serum glucose ≥200mg/dL (OR=1.63, 95% CI: 0.48-5.55), although the results did not attain statistical significance.Conclusion: In summary, our finding of a positive association between obesity and liver cancer suggests that a higher BMI may increase the risk of liver cancer in the US, for both sexes and all race/ethnicities. [ABSTRACT FROM AUTHOR]

Concerns about high caffeine intake and coffee as a vehicle for added fat and sugar have raised questions about the net impact of coffee on health. Although inverse associations have been observed for overall mortality, data for cause-specific mortality are sparse. Additionally, few studies have considered exclusively decaffeinated coffee intake or use of coffee additives. Coffee intake was assessed at baseline by self-report in the Prostate, Lung, Colo-rectal and Ovarian Cancer Screening Trial. Hazard ratios were estimated using Cox proportional hazards models. Among 90,317 US adults without cancer at study baseline (1998-2001) or history of cardiovascular disease at study enrollment (1993-2001), 8,718 deaths occurred during 805,644 person-years of follow-up from 1998 through 2009. Following adjustment for smoking and other potential confounders, coffee drinkers, as compared with nondrinkers, had lower hazard ratios for overall mortality (<1 cup/day: hazard ratio (HR) = 0.99 (95% confidence interval (CI): 0.92, 1.07); 1 cup/day: HR = 0.94 (95% CI: 0.87, 1.02); 2-3 cups/day: HR = 0.82 (95% CI: 0.77, 0.88); 4-5 cups/ day: HR = 0.79 (95% CI: 0.72, 0.86); ≥6 cups/day: HR = 0.84 (95% CI: 0.75, 0.95)). Similar findings were observed for decaffeinated coffee and coffee additives. Inverse associations were observed for deaths from heart disease, chronic respiratory diseases, diabetes, pneumonia and influenza, and intentional self-harm, but not cancer. Coffee may reduce mortality risk by favorably affecting inflammation, lung function, insulin sensitivity, and depression. [ABSTRACT FROM AUTHOR]

Background: Chronic infection with the hepatitis B virus and obesity may both contribute synergistically to liver disease, although relatively few studies have investigated this hypothesis. Therefore, in this study, we evaluated the relationship between central obesity and the liver stiffness in the Golestan Hepatitis B cohort study (GHBCS). Methods: Our study included 304 chronic hepatitis B (CHB) patients enrolled from GHBCS. Liver stiffness measurement (LSM) and laboratory tests were performed after a follow-up of 4 years (2012). The hepatitis B viral load was measured at the baseline and follow-up using the real-time PCR method. VNfeist circumference ≥ 102 cm in men and ≥ 89 cm in women (central obesity) was considered to be abnormal. Advanced liver stiffness (ALS) was defined as LSM ≥ 8 KPa. Statistical analysis was performed using SPSS-V17. Logistic regression was used to test predictors of advanced liver stiffness (LSM ≥ 8 KPa). Linear regression was used to test the predictive value of variables in ALT (as a continuous variable). P-value of less than 0.05 was considered statistically significant. Results: Among these CHB patients, 19 (7.4%) cases with a mean (±SD) age of 49.5 (±6.3) developed ALS after 4 years of follow-up. Multivariate analysis showed a significant predictive role of central obesity and viral load in ALS. Conclusions: Central obesity is related to the liver stiffness in chronic hepatitis B patients. [ABSTRACT FROM AUTHOR]

Background: Chronic infection with the hepatitis B virus and obesity may both contribute synergistically to liver disease, although relatively few studies have investigated this hypothesis. Therefore, in this study, we evaluated the relationship between central obesity and the liver stiffness in the Golestan Hepatitis B cohort study (GHBCS). Methods: Our study included 304 chronic hepatitis B (CHB) patients enrolled from GHBCS. Liver stiffness measurement (LSM) and laboratory tests were performed after a follow-up of 4 years (2012). The hepatitis B viral load was measured at the baseline and follow-up using the real-time PCR method. VNfeist circumference ≥ 102 cm in men and ≥ 89 cm in women (central obesity) was considered to be abnormal. Advanced liver stiffness (ALS) was defined as LSM ≥ 8 KPa. Statistical analysis was performed using SPSS-V17. Logistic regression was used to test predictors of advanced liver stiffness (LSM ≥ 8 KPa). Linear regression was used to test the predictive value of variables in ALT (as a continuous variable). P-value of less than 0.05 was considered statistically significant. Results: Among these CHB patients, 19 (7.4%) cases with a mean (±SD) age of 49.5 (±6.3) developed ALS after 4 years of follow-up. Multivariate analysis showed a significant predictive role of central obesity and viral load in ALS. Conclusions: Central obesity is related to the liver stiffness in chronic hepatitis B patients. [ABSTRACT FROM AUTHOR]

In this issue of the Journal, Wyss et al. (Am J Epidemiol. 2016;184(10):703-716) describe the association between use of smokeless tobacco and head and neck cancer in 11 US case-control studies. Despite use by an estimated 300 million people worldwide and prior evidence for a causal association with cancer, these products remain understudied. Data are particularly needed for persons who do not use cigarettes or other smoking tobacco products. With 6,772 cancer cases and 8,375 controls, the current study is larger than previous efforts, allowing evaluation of associations among never cigarette smokers. Importantly, snuff use was positively associated with head and neck cancer, particularly for cancers of the oral cavity, whereas associations were weaker for chewing tobacco. Associations were observed among never cigarette smokers but not among ever cigarette smokers. Yet, despite the large sample size, only 44 cases and 62 controls had used snuff and only 61 cases and 96 controls had used chewing tobacco in the absence of cigarettes, precluding detailed examinations of dose response and cessation. Future studies set in high-prevalence populations with detailed assessment of lifetime use are needed to better understand the cancer risks of exclusive smokeless tobacco use and dual use of smokeless tobacco with other tobacco products, including cigarettes. [ABSTRACT FROM AUTHOR]

Gallstones and cholecystectomy may be related to digestive system cancer through inflammation, altered bile flux, and changes in metabolic hormone levels. Although gallstones are recognized causes of gallbladder cancer, associations with other cancers of the digestive system are poorly established. We used the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database (1992–2005), which includes 17 cancer registries that cover approximately 26% of the US population, to identify first primary cancers (n = 236,850) occurring in persons aged ≥66 years and 100,000 cancer-free population-based controls frequency-matched by calendar year, age, and gender. Odds ratios and 95% confidence intervals were calculated using logistic regression analysis, adjusting for the matching factors. Gallstones and cholecystectomy were associated with increased risk of noncardia gastric cancer (odds ratio (OR) = 1.21 (95% confidence interval (CI): 1.11, 1.32) and OR = 1.26 (95% CI: 1.13, 1.40), respectively), small-intestine carcinoid (OR = 1.27 (95% CI: 1.01, 1.60) and OR = 1.78 (95% CI: 1.41, 2.25)), liver cancer (OR = 2.35 (95% CI: 2.18, 2.54) and OR = 1.26 (95% CI: 1.12, 1.41)), and pancreatic cancer (OR = 1.24 (95% CI: 1.16, 1.31) and OR = 1.23 (95% CI: 1.15, 1.33)). Colorectal cancer risk associated with gallstones and cholecystectomy decreased with increasing distance from the common bile duct (P-trend < 0.001). Hence, gallstones and cholecystectomy are associated with the risk of cancers occurring throughout the digestive tract. [ABSTRACT FROM PUBLISHER]

In China, esophageal cancer is the fourth leading cause of cancer death where essentially all cases are histologically esophageal squamous cell carcinoma (ESCC), in contrast to esophageal adenocarcinoma in the West. Globally, ESCC is 2.4 times more common among men than women and recently it has been suggested that sex hormones may be associated with the risk of ESCC. We examined the association between genetic variants in sex hormone metabolic genes and ESCC risk in a population from north central China with high-incidence rates. A total of 1026 ESCC cases and 1452 controls were genotyped for 797 unique tag single-nucleotide polymorphisms (SNPs) in 51 sex hormone metabolic genes. SNP-, gene- and pathway-based associations with ESCC risk were evaluated using unconditional logistic regression adjusted for age, sex and geographical location and the adaptive rank truncated product (ARTP) method. Statistical significance was determined through use of permutation for pathway- and gene-based associations. No associations were observed for the overall sex hormone metabolic pathway (P = 0.14) or subpathways (androgen synthesis: P = 0.30, estrogen synthesis: P = 0.15 and estrogen removal: P = 0.19) with risk of ESCC. However, six individual genes (including SULT2B1, CYP1B1, CYP3A7, CYP3A5, SHBG and CYP11A1) were significantly associated with ESCC risk (P < 0.05). Our examination of genetic variation in the sex hormone metabolic pathway is consistent with a potential association with risk of ESCC. These positive findings warrant further evaluation in relation to ESCC risk and replication in other populations. [ABSTRACT FROM AUTHOR]

Objective The incidence of oesophageal adenocarcinoma (EAC) has increased rapidly over the past 40 years and accumulating evidence suggests that obesity, as measured by body mass index (BMI), is a major risk factor. It remains unclear whether abdominal obesity is associated with EAC and gastric adenocarcinoma. Design Cox proportional hazards regression was used to examine associations between overall and abdominal obesity with EAC and gastric adenocarcinoma among 218 854 participants in the prospective NIHeAARP cohort. Results 253 incident EAC, 191 gastric cardia adenocarcinomas and 125 gastric non-cardia adenocarcinomas accrued to the cohort. Overall obesity (BMI) was positively associated with EAC and gastric cardia adenocarcinoma risk (highest ($35 kg/m2) vs referent (18.5e<25 kg/m2); HR 2.11, 95% CI 1.09 to 4.09 and HR 3.67, 95% CI 2.00 to 6.71, respectively). Waist circumference was also positively associated with EAC and gastric cardia adenocarcinoma risk (highest vs referent; HR 2.01, 95% CI 1.35 to 3.00 and HR 2.22, 95% CI 1.43 to 3.47, respectively), whereas waist-to-hip ratio (WHR) was positively associated with EAC risk only (highest vs referent; HR 1.81, 95% CI 1.24 to 2.64) and persisted in patients with normal BMI (18.5e<25 kg/ m2). Mutual adjustment of WHR and BMI attenuated both, but did not eliminate the positive associations for either with risk of EAC. In contrast, the majority of the anthropometric variables were not associated with adenocarcinomas of the gastric non-cardia. Conclusion Overall obesity was associated with a higher risk of EAC and gastric cardia adenocarcinoma, whereas abdominal obesity was found to be associated with increased EAC risk; even in people with normal BMI. [ABSTRACT FROM AUTHOR]

Background: Coffee is one of the most widely consumed beverages, but the association between coffee consumption and the risk of death remains unclear. Methods: We examined the association of coffee drinking with subsequent total and cause-specific mortality among 229,119 men and 173,141 women in the National Institutes of Health–AARP Diet and Health Study who were 50 to 71 years of age at baseline. Participants with cancer, heart disease, and stroke were excluded. Coffee consumption was assessed once at baseline. Results: During 5,148,760 person-years of follow-up between 1995 and 2008, a total of 33,731 men and 18,784 women died. In age-adjusted models, the risk of death was increased among coffee drinkers. However, coffee drinkers were also more likely to smoke, and, after adjustment for tobacco-smoking status and other potential confounders, there was a significant inverse association between coffee consumption and mortality. Adjusted hazard ratios for death among men who drank coffee as compared with those who did not were as follows: 0.99 (95% confidence interval [CI], 0.95 to 1.04) for drinking less than 1 cup per day, 0.94 (95% CI, 0.90 to 0.99) for 1 cup, 0.90 (95% CI, 0.86 to 0.93) for 2 or 3 cups, 0.88 (95% CI, 0.84 to 0.93) for 4 or 5 cups, and 0.90 (95% CI, 0.85 to 0.96) for 6 or more cups of coffee per day (P<0.001 for trend); the respective hazard ratios among women were 1.01 (95% CI, 0.96 to 1.07), 0.95 (95% CI, 0.90 to 1.01), 0.87 (95% CI, 0.83 to 0.92), 0.84 (95% CI, 0.79 to 0.90), and 0.85 (95% CI, 0.78 to 0.93) (P<0.001 for trend). Inverse associations were observed for deaths due to heart disease, respiratory disease, stroke, injuries and accidents, diabetes, and infections, but not for deaths due to cancer. Results were similar in subgroups, including persons who had never smoked and persons who reported very good to excellent health at baseline. Conclusions: In this large prospective study, coffee consumption was inversely associated with total and cause-specific mortality. Whether this was a causal or associational finding cannot be determined from our data. (Funded by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics.) [ABSTRACT FROM PUBLISHER]

The article focuses on a study about the relationship between smoking and the risk of developing bladder cancer. It notes that tobacco smoking has been established as a risk factor for bladder cancer, adding that while tar and nicotine concentrations have been reduced in cigarettes, concentrations of certain carcinogens such as β-napthylamine and nitrosamine have been increased. Results show that cigarette smoking is a risk factor for such cancer in men and women while smoking cessation leads to a lesser risk of developing the disease. It discusses factors behind the strong cigarette smoking-bladder cancer relationship, one is increased awareness among smokers that results to earlier diagnostic workup.

Background and aims: Alcohol intake is a strong and well established risk factor for oesophageal squamous cell carcinoma (OSCC), but the association with oesophageal adenocarcinoma (OA) or adjacent tumours of the oesophagogastric junction (OGJA), remains unclear. Therefore, the association of alcohol intake with OSCC, OA, and OGJA was determined in nine caseecontrol studies and two cohort studies of the Barrett's Esophagus and Esophageal Adenocarcinoma Consortium (BEACON). Materials and methods: Information was collected on alcohol intake, age, sex, education, body mass index, gastro-oesophageal reflux, and tobacco smoking from each study. Along with 10 854 controls, 1821 OA, and 1837 OGJA, seven studies also collected OSCC cases (n¼1016). Study specific ORs and 95% CIs were calculated from multivariate adjusted logistic regression models for alcohol intake in categories compared to non-drinkers. Summary risk estimates were obtained by random effects models. Results: No increase was observed in the risk of OA or OGJA for increasing levels of any of the alcohol intake measures examined. ORs for the highest frequency category ($7 drinks per day) were 0.97 (95% CI 0.68 to 1.36) for OA and 0.77 (95% CI ¼ 0.54 to 1.10) for OGJA. Suggestive findings linked moderate intake (eg, 0.5 to <1 drink per day) to decreased risk of OA (OR 0.63, 95% CI 0.41 to 0.99) and OGJA (OR 0.78, 95% CI 0.62 to 0.99). In contrast, alcohol intake was strongly associated with increased risk of OSCC (OR for $7 drinks per day 9.62, 95% CI 4.26 to 21.71). Conclusions: In contrast to OSCC, higher alcohol consumption was not associated with increased risk of either OA or OGJA. The apparent inverse association observed with moderate alcohol intake should be evaluated in future prospective studies. [ABSTRACT FROM AUTHOR]

OBJECTIVES:Red and processed meats could increase cancer risk through several potential mechanisms involving iron, heterocyclic amines, polycyclic aromatic hydrocarbons, and N-nitroso compounds. Although there have been multiple studies of meat and colorectal cancer, other gastrointestinal malignancies are understudied.METHODS:We estimated hazard ratios (HR) and 95% confidence intervals (CI) for the association between meat, meat components, and meat cooking by-products and risk of esophageal or gastric cancer in a large cohort study. During ∼10 years of follow-up, we accrued 215 esophageal squamous cell carcinomas, 630 esophageal adenocarcinomas, 454 gastric cardia adenocarcinomas, and 501 gastric non-cardia adenocarcinomas.RESULTS:Red meat intake was positively associated with esophageal squamous cell carcinoma (HR for the top versus bottom quintile=1.79, 95% CI: 1.07-3.01, P for trend=0.019). Individuals in the highest intake quintile of 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) had an increased risk for gastric cardia cancer (HR=1.44, 95% CI: 1.01-2.07, P for trend=0.104). Furthermore, those in the highest quintile of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), or heme iron intake had a suggestive increased risk for esophageal adenocarcinoma (HR=1.35, 95% CI: 0.97-1.89, P for trend=0.022; HR=1.45, 95% CI: 0.99-2.12, P for trend=0.463; or HR=1.47, 95% CI: 0.99-2.20, P for trend=0.063, respectively). Benzo[a]pyrene, nitrate, and nitrite were not associated with esophageal or gastric cancer.CONCLUSIONS:We found positive associations between red meat intake and esophageal squamous cell carcinoma, and between DiMeIQx intake and gastric cardia cancer. [ABSTRACT FROM AUTHOR]

Background Several plausible mechanisms, including fat, iron, heterocyclic amines, and N-nitroso compounds, link meat intake with chronic liver disease (CLD) and hepatocellular carcinoma (HCC). Few studies have investigated these associations. Methods We prospectively examined the relationship between meat and associated exposures with CLD mortality (n = 551; not including HCC) and HCC incidence (n = 338) in 495 006 men and women of the National Institutes of Health-AARP Diet and Health Study. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the fifth (Q5) vs the first (Q1) quintile were estimated from multivariable adjusted Cox proportional hazards regression models. All tests of statistical significance were two-sided. Results We found inverse associations between white meat and risk of CLD (HR = 0.52, 95% CI = 0.39 to 0.70, 7.5 vs 18.2 cases per 100 000 person-years) and HCC (HR = 0.52, 95% CI = 0.36 to 0.77, 5.8 vs 14.3 cases per 100 000 personyears). Red meat was associated with higher risk of CLD (HR = 2.59, 95% CI = 1.86 to 3.61, 22.3 vs 6.2 cases per 100 000 person-years) and HCC (HR = 1.74, 95% CI = 1.16 to 2.61, 14.9 vs 5.7 cases per 100 000 person-years). Among fat types, results were strongest for saturated fat (for CLD, HR = 3.50, 95% CI = 2.48 to 4.96, 23.0 vs 6.5 cases per 100 000 person-years; for HCC, HR = 1.87, 95% CI = 1.23 to 2.85, 14.5 vs 6.3 cases per 100 000 personyears). After mutual adjustment, risk estimates persisted for saturated fat, red meat, and white meat. Heme iron, processed meat, nitrate, and nitrite were positively associated with CLD but not with HCC. Individual heterocyclic amines, 2-amino-3,4,8-trimethylimidazo[4,5,-f]quinoxaline (DiMeIQx), 2-amino-3,8-dimethylimidazo[4,5-f] quinoxaline (MeIQx), and 2-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine (PhIP), were not associated with either outcome. Conclusion Our results suggest that red meat and saturated fat may be associated with increased CLD and HCC risk, whereas white meat may be associated with reduced risk. [ABSTRACT FROM AUTHOR]

We conducted a genome-wide association study of gastric cancer and esophageal squamous cell carcinoma (ESCC) in ethnic Chinese subjects in which we genotyped 551,152 SNPs. We report a combined analysis of 2,240 gastric cancer cases, 2,115 ESCC cases and 3,302 controls drawn from five studies. In logistic regression models adjusted for age, sex and study, multiple variants at 10q23 had genome-wide significance for gastric cancer and ESCC independently. A notable signal was rs2274223, a nonsynonymous SNP located in PLCE1, for gastric cancer (P = 8.40 × 10−9; per-allele odds ratio (OR) = 1.31) and ESCC (P = 3.85 × 10−9; OR = 1.34). The association with gastric cancer differed by anatomic subsite. For tumors in the cardia the association was stronger (P = 4.19 × 10−15; OR = 1.57), and for those in the noncardia stomach it was absent (P = 0.44; OR = 1.05). Our findings at 10q23 could provide insight into the high incidence of both cancers in China. [ABSTRACT FROM AUTHOR]

The article reports on the study which establishes the association of menstrual and reproductive factors with the cancers in the upper gastrointestinal tract (UGI). It notes that the UGI tract cancers risks which involve the head and neck, esophagus, and stomach are higher in men to develop adenicarcinomas and squamous cell carcinomas. It implies that the higher levels of progesterone and estrogen levels in women could explain the lower incidence rates of UGI cancers in women than in men.

Little is known about the association between alcohol and breast cancer by different tumor characteristics. The study consisted of 184,418 postmenopausal women aged 50–71 years in the National Institutes of Health-AARP Diet and Health Study (1995–2003). Alcohol use, diet, and potential risk factors for cancer were assessed with a mailed questionnaire at baseline. The relative risks and 95% confidence intervals were estimated by using Cox proportional hazards regression. Breast cancer cases and estrogen receptor and progesterone receptor status were identified through linkage to state cancer registries. During an average of 7 years of follow-up, 5,461 breast cancer cases were identified. Alcohol was significantly positively associated with total breast cancer: Even a moderate amount of alcohol (>10 g/day) significantly increased breast cancer risk. In a comparison of >35 g versus 0 g/day, the multivariate relative risks were 1.35 (95% confidence interval (CI): 1.17, 1.56) for total breast cancer, 1.46 (95% CI: 1.22, 1.75) for ductal tumors, and 1.52 (95% CI: 0.95, 2.44) for lobular tumors. The multivariate relative risks for estrogen receptor-positive/progesterone receptor-positive, estrogen receptor-positive/progesterone receptor-negative, and estrogen receptor-negative/progesterone receptor-negative tumors were 1.46 (95% CI: 1.12, 1.91) for >35 g versus 0 g/day, 1.13 (95% CI: 0.73, 1.77) for >20 g versus 0 g/day, and 1.21 (95% CI: 0.79, 1.84) for >20 g versus 0 g/day, respectively. Moderate consumption of alcohol was associated with breast cancer, specifically hormone receptor-positive tumors. [ABSTRACT FROM PUBLISHER]

Summary: Background: Whether women are more susceptible than men to lung cancer caused by cigarette smoking has been controversial. To address this question, we aimed to compare incidence rates of lung cancer by stratum of smoking use in men and women of the National Institutes of Health (NIH)-AARP cohort. Methods: Participants in the NIH-AARP Diet and Health study responded to a postal questionnaire between Oct 13, 1995, and May 6, 1996, and were followed up until Dec 31, 2003. The questionnaire asked participants about their past and current smoking status, demographics, alcohol intake, tobacco smoking, physical activity, and included a food-frequency questionnaire of 124 items. Incident lung cancers were identified by linkage to individual state cancer registries. We present age-standardised incidence rates for cancer and multivariate hazard ratios (HRs) adjusted for potential confounders, with 95% CIs. This study conforms to the STROBE guidelines. Findings: 279 214 men and 184 623 women from eight states in the USA aged 50–71 years at study baseline were included in this analysis. During follow-up, lung cancers occurred in 4097 men and 2237 women. Incidence rates were 20·3 (95% CI 16·3–24·3) per 100 000 person-years in men who had never smoked (99 cancers) and 25·3 (21·3–29·3) in women who had never smoked (152 cancers); for this group, the adjusted HR for lung cancer was 1·3 (1·0–1·8) for women compared with men. Smoking was associated with increased risk of lung cancer in men and women. The incidence rate of current smokers who smoked more than two packs per day was 1259·2 (1035·0–1483·3) in men and 1308·9 (924·2–1693·6) in women. In current smokers, in a model adjusted for typical smoking dose, the HR was 0·9 (0·8–0·9) for women compared with men. For former smokers, in a model adjusted for years of cessation and typical smoking dose, the HR was 0·9 (0·9–1·0) for women compared with men. Incidence rates of adenocarcinoma, small-cell carcinoma, and undifferentiated tumours were similar in men and women; incidence rates of squamous tumours in men were about twice that in women. Interpretation: Our findings suggest that women are not more susceptible than men to the carcinogenic effects of cigarette smoking in the lung. In smokers, incidence rates tended to be higher in men than women with comparable smoking histories, but differences were modest; smoking was strongly associated with lung cancer risk in both men and women. Future studies should confirm whether incidence rates are indeed higher in women who have never smoked than in men who have never smoked. Funding: Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics, Bethesda, MD, USA. [Copyright &y& Elsevier]

Abstract: The incidence of oesophageal adenocarcinoma (EADC) is rapidly increasing in Western countries and obesity is thought to be a major risk factor. We examined the association between BMI and EADC, gastric cardia adenocarcinoma and gastric non-cardia adenocarcinoma in a cohort of approximately 500,000 people in the United States (US). We used Cox proportional hazards regression to estimate hazard ratios (HR) and 95% confidence intervals (CI) with control for many potential confounders. We found that compared to people with a BMI of 18.5–25kg/m2, a BMI ⩾35 was associated with significantly increased risk of EADC, HR (95% CI)=2.27 (1.44–3.59) and gastric cardia adenocarcinoma 2.46 (1.60–3.80), but not gastric non-cardia adenocarcinoma 0.84 (0.50–1.42). Using non-linear models, we found that higher BMI was associated with increased risk of EADC even within the normal BMI. Increased adiposity was associated with higher risk of EADC even within the normal weight range. [Copyright &y& Elsevier]

Background: Gastric cancer incidence rates are consistently lower in women than men in both high and low-risk regions worldwide. Sex hormones, such as progesterone and estrogen, may protect women against gastric cancer. Objective: To investigate the association of menstrual and reproductive factors and gastric cancer risk. Methods: These associations were prospectively investigated in 73 442 Shanghai women. After 419 260 person-years of follow-up, 154 women were diagnosed with gastric cancer. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using Cox proportional hazards models adjusted for age, body mass index, education, income, and cigarette use. Results: No associations were observed between gastric cancer risk and age of menarche, number of children, breast feeding, or oral contraceptive use. In contrast, associations were observed with age of menopause (HR 0.80 per five-year increase in menopausal age, 95% CI 0.66-0.97), years of fertility (participants with less than 30 years of fertility were at increased risk compared with those with 30-36 years of fertility, HR 1 .90, 95% CI 1.25-2.90), years since menopause (HR 1.26 per five years, 95% CI 1.03-1.53), and intrauterine device use (HR for users 1.61, 95% CI 1.08-2.39). Conclusions: These results support the hypothesis that female hormones play a protective role in gastric cancer risk. [ABSTRACT FROM AUTHOR]

The article focuses on the findings of a study that examined the association between cigarette smoking and cancers of the head and neck in women. The authors used age-standardized incidence rates and hazard ratios from Cox models adjusted for other risk factors for head and neck cancers. It notes that incidence rates of head and neck cancer were higher in male smokers than female smokers, but smoking may explain a higher proportion of head and neck cancer in women than in men.

Coffee drinking has been inversely associated with liver cancer consistently in prospective studies. Yet, the specific compounds underlying this association, and whether associations vary by preparation method, are unknown. Associations with other sites within the gastrointestinal tract are also unclear. A recent study by Tran et al. leverages the resources of the UK Biobank to begin answering these questions, and suggests important avenues for future work. [ABSTRACT FROM AUTHOR]

The editorialists discuss Yu and coworkers' findings in light of what is known about thermal irritation and cancer. [ABSTRACT FROM AUTHOR]

The human oral microbiome may alter oral and systemic disease risk. Consuming high sugar content beverages (HSB) can lead to caries development by altering the microbial composition in dental plaque, but little is known regarding HSB-specific oral microbial alterations. Therefore, we conducted a large, population-based study to examine associations of HSB intake with oral microbiome diversity and composition. Using mouthwash samples of 989 individuals in two nationwide U.S. cohorts, bacterial 16S rRNA genes were amplified, sequenced, and assigned to bacterial taxa. HSB intake was quantified from food frequency questionnaires as low (< 1 serving/week), medium (1–3 servings/week), or high (> 3 servings/week). We assessed overall bacterial diversity and presence of specific taxa with respect to HSB intake in each cohort separately and combined in a meta-analysis. Consistently in the two cohorts, we found lower species richness in high HSB consumers (> 3 cans/week) (p = 0.027), and that overall bacterial community profiles differed from those of non-consumers (PERMANOVA p = 0.040). Specifically, presence of a network of commensal bacteria (Lachnospiraceae, Peptostreptococcaceae, and Alloprevotella rava) was less common in high compared to non-consumers, as were other species including Campylobacter showae, Prevotella oulorum, and Mycoplasma faucium. Presence of acidogenic bacteria Bifodobacteriaceae and Lactobacillus rhamnosus was more common in high consumers. Abundance of Fusobacteriales and its genus Leptotrichia, Lachnoanaerobaculum sp., and Campylobacter were lower with higher HSB consumption, and their abundances were correlated. No significant interaction was found for these associations with diabetic status or with microbial markers for caries (S. mutans) and periodontitis (P. gingivalis). Our results suggest that soft drink intake may alter the salivary microbiota, with consistent results across two independent cohorts. The observed perturbations of overrepresented acidogenic bacteria and underrepresented commensal bacteria in high HSB consumers may have implications for oral and systemic disease risk. [ABSTRACT FROM AUTHOR]

Background Reducing cigarettes per day may lower the risk of lung cancer compared with continuing to smoke at the same intensity. Other changes in smoking behaviors, such as increasing cigarette consumption or quitting for a period and relapsing, may also affect lung cancer risk. Methods We examined changes in smoking status and cigarettes per day among 24 613 Finnish male smokers aged 50-69 years who participated in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Longitudinal data on smoking were collected during study follow-up visits 3 times a year (approximately every 4 months) between 1985 and 1993. Incident lung cancer patients through 2012 were identified by the Finnish Cancer Registry. Risk ratios (RRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression. Results Compared with smoking 20 cigarettes per day continuously across the intervention period, reducing an average of 5 cigarettes per day per year while smoking was associated with a 20% lower risk of lung cancer (95% CI = 0.71 to 0.90). A substantially lower risk of lung cancer was also observed when participants smoked at 50% (RR = 0.72, 95% CI = 0.57 to 0.90) and 10% (RR = 0.55, 95% CI = 0.36 to 0.83) of study visits, relative to smoked at 100% of study visits. Conclusions Smokers may lower their risk of lung cancer by reducing smoking intensity (cigarettes per day while smoking) and the time they smoke. However, quitting smoking completely is the most effective way for smokers to reduce their risk of lung cancer. [ABSTRACT FROM AUTHOR]

Background In the United States, lung cancer death rates have been declining for decades, primarily as a result of pronounced decreases in cigarette smoking. It is unclear, however, whether there have been similar declines in mortality rates of lung cancer unrelated to smoking. We estimated trends in US lung cancer death rates attributable and not attributable to smoking from 1991 to 2018. Methods The study included 30- to 79-year-olds in the National Health Interview Survey who were linked to the National Death Index, 1991-2014. Adjusted hazard ratios for smoking status and lung cancer death were estimated, and age-specific population attributable fractions were calculated. Annual population attributable fractions were multiplied by annual US national lung cancer mortality, partitioning rates into smoking-attributable and smoking-unrelated lung cancer deaths. All statistical tests were 2-sided. Results During 1991-2018, the proportion of never smokers increased among both men (35.1%-54.6%) and women (54.0%-65.4%). Compared with those who had ever smoked, those who had never smoked had 86% lower risk (hazard ratio = 0.14; 95% confidence interval [CI] = 0.12 to 0.16) of lung cancer death. The fraction of lung cancer deaths attributable to smoking decreased from 81.4% (95% CI = 78.9 to 81.4) to 74.7% (95% CI = 78.1 to 71.4). Smoking-attributable lung cancer death rates declined 2.7% per year (95% CI = ‒2.9% to ‒2.5%) and smoking-unrelated lung cancer death rates declined 1.8% per year (95% CI = ‒2.0% to ‒1.5%); these declines have accelerated in recent years. Conclusions An increasing proportion of lung cancer deaths are unrelated to smoking based on declines in smoking prevalence. Smoking-unrelated lung cancer death rates have declined, however, perhaps because of decreases in secondhand smoke and air pollution exposure as well as treatment improvements. [ABSTRACT FROM AUTHOR]

Background: The hygiene hypothesis posits that microbial exposure reduces risk of asthma and other respiratory-related diseases. Helicobacter pylori and hepatitis A virus (HAV) are common fecal–oral infections. Our study aimed to examine associations of seropositivity to these agents with asthma in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Methods: A total of 12,471 HCHS/SOL participants with baseline data on self-reported physician-diagnosed asthma, and antibodies anti-H. pylori and anti-HAV were included in this cross-sectional analysis. Multivariable logistic regression models were used to estimate the odds ratios and 95% confidence intervals for the overall associations of seropositivity to each agent with asthma. Analyses were also stratified by Hispanic/Latino background. Effect modification by smoking status and nativity were tested. An analysis restricted to individuals with spirometry-defined chronic obstructive pulmonary disease (COPD) was also considered. Results: The weighted overall prevalence of asthma was 16.6%. The weighted seroprevalence of H. pylori was 56.6% and of HAV was 76.6%, and they significantly differed by Hispanic/Latino background. After accounting for age, sex, education and other key confounders, we found no associations between H. pylori or HAV seropositivity with asthma (with and without COPD), either for all individuals combined or for any of the six specific backgrounds. There were no significant interactions by smoking and nativity. Conclusion: Our findings did not provide support for the role of H. pylori or HAV, as evidence of the hygiene hypothesis in asthma among the large and diverse Hispanic/Latino populations of the HCHS/SOL. Trial registration NCT02060344 [ABSTRACT FROM AUTHOR]

Background: Coffee consumption has been associated with a reduced risk of some cancers, but the evidence for renal cell carcinoma (RCC) is inconclusive. We investigated the relationship between coffee and RCC within a large cohort.Methods: Coffee intake was assessed at baseline in the National Institutes of Health-American Association of Retired Persons Diet and Health Study. Among 420 118 participants eligible for analysis, 2674 incident cases were identified. We fitted Cox-regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for coffee consumption vs non-drinkers.Results: We observed HRs of 0.94 (95% CI 0.81, 1.09), 0.94 (0.81, 1.09), 0.80 (0.70, 0.92) and 0.77 (0.66, 0.90) for usual coffee intake of <1, 1, 2-3 and ≥4 cups/day, respectively (Ptrend = 0.00003). This relationship was observed among never-smokers (≥4 cups/day: HR 0.62, 95% CI 0.46, 0.83; Ptrend = 0.000003) but not ever-smokers (HR 0.85, 95% CI 0.70, 1.05; Ptrend = 0.35; Pinteraction = 0.0009) and remained in analyses restricted to cases diagnosed >10 years after baseline (HR 0.65, 95% CI 0.51, 0.82; Ptrend = 0.0005). Associations were similar between subgroups who drank predominately caffeinated or decaffeinated coffee (Pinteraction = 0.74).Conclusion: In this investigation of coffee and RCC, to our knowledge the largest to date, we observed a 20% reduced risk for intake of ≥2 cups/day vs not drinking. Our findings add RCC to the growing list of cancers for which coffee consumption may be protective. [ABSTRACT FROM AUTHOR]

Background: Recent therapeutic advances and screening technologies have improved survival among patients with lung cancer, who are now at high risk of developing second primary lung cancer (SPLC). Recently, an SPLC risk‐prediction model (called SPLC‐RAT) was developed and validated using data from population‐based epidemiological cohorts and clinical trials, but real‐world validation has been lacking. The predictive performance of SPLC‐RAT was evaluated in a hospital‐based cohort of lung cancer survivors. Methods: The authors analyzed data from 8448 ever‐smoking patients diagnosed with initial primary lung cancer (IPLC) in 1997–2006 at Mayo Clinic, with each patient followed for SPLC through 2018. The predictive performance of SPLC‐RAT and further explored the potential of improving SPLC detection through risk model‐based surveillance using SPLC‐RAT versus existing clinical surveillance guidelines. Results: Of 8448 IPLC patients, 483 (5.7%) developed SPLC over 26,470 person‐years. The application of SPLC‐RAT showed high discrimination area under the receiver operating characteristics curve: 0.81). When the cohort was stratified by a 10‐year risk threshold of ≥5.6% (i.e., 80th percentile from the SPLC‐RAT development cohort), the observed SPLC incidence was significantly elevated in the high‐risk versus low‐risk subgroup (13.1% vs. 1.1%, p < 1 × 10–6). The risk‐based surveillance through SPLC‐RAT (≥5.6% threshold) outperformed the National Comprehensive Cancer Network guidelines with higher sensitivity (86.4% vs. 79.4%) and specificity (38.9% vs. 30.4%) and required 20% fewer computed tomography follow‐ups needed to detect one SPLC (162 vs. 202). Conclusion: In a large, hospital‐based cohort, the authors validated the predictive performance of SPLC‐RAT in identifying high‐risk survivors of SPLC and showed its potential to improve SPLC detection through risk‐based surveillance. Plain Language Summary: Lung cancer survivors have a high risk of developing second primary lung cancer (SPLC).However, no evidence‐based guidelines for SPLC surveillance are available for lung cancer survivors.Recently, an SPLC risk‐prediction model was developed and validated using data from population‐based epidemiological cohorts and clinical trials, but real‐world validation has been lacking.Using a large, real‐world cohort of lung cancer survivors, we showed the high predictive accuracy and risk‐stratification ability of the SPLC risk‐prediction model.Furthermore, we demonstrated the potential to enhance efficiency in detecting SPLC using risk model‐based surveillance strategies compared to the existing consensus‐based clinical guidelines, including the National Comprehensive Cancer Network. Given the rapidly growing number of lung cancer survivors who are now at high risk of developing second primary lung cancer (SPLC), previous studies have identified SPLC risk factors and developed SPLC risk‐prediction models, but they lack insight into real‐world validation to help improve clinical decision‐making in SPLC surveillance for lung cancer survivors. Using a large, hospital‐based real‐world cohort of lung cancer survivors, the authors validated the predictive accuracy of an SPLC risk‐prediction model (area under the curve of 0.81), that can identify high‐risk lung cancer survivors for SPLC and can be incorporated into clinical decision‐making for SPLC surveillance to improve the systematic management of lung cancer survivors. [ABSTRACT FROM AUTHOR]

Background The incidence of differentiated thyroid cancer (DTC) is higher in women than in men but whether sex steroid hormones contribute to this difference remains unclear. Studies of reproductive and hormonal factors and thyroid cancer risk have provided inconsistent results. Methods Original data from 1 252 907 women in 16 cohorts in North America, Europe, Australia and Asia were combined to evaluate associations of DTC risk with reproductive and hormonal factors. Multivariable-adjusted Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% CIs. Results During follow-up, 2142 women were diagnosed with DTC. Factors associated with higher risk of DTC included younger age at menarche (<10 vs 10–11 years; HR, 1.28; 95% CI, 1.00–1.64), younger (<40; HR, 1.31; 95% CI, 1.05–1.62) and older (≥55; HR, 1.33; 95% CI, 1.05–1.68) ages at menopause (vs 40–44 years), ever use of menopausal hormone therapy (HR, 1.16; 95% CI, 1.02–1.33) and previous hysterectomy (HR, 1.25; 95% CI, 1.13–1.39) or bilateral oophorectomy (HR, 1.14; 95% CI, 1.00–1.29). Factors associated with lower risk included longer-term use (≥5 vs <5 years) of oral contraceptives (HR, 0.86; 95% CI, 0.76–0.96) among those who ever used oral contraception and baseline post-menopausal status (HR, 0.82; 95% CI, 0.70–0.96). No associations were observed for parity, duration of menopausal hormone therapy use or lifetime number of reproductive years or ovulatory cycles. Conclusions Our study provides some evidence linking reproductive and hormonal factors with risk of DTC. Results should be interpreted cautiously considering the modest strength of the associations and potential for exposure misclassification and detection bias. Prospective studies of pre-diagnostic circulating sex steroid hormone measurements and DTC risk may provide additional insight. [ABSTRACT FROM AUTHOR]

Background Fine particulate matter (PM2.5) has been inconsistently associated with breast cancer incidence, however, few studies have considered historic exposure when levels were higher. Methods Outdoor residential PM2.5 concentrations were estimated using a nationwide spatiotemporal model for women in the National Institutes of Health–AARP Diet and Health Study, a prospective cohort located in 6 states (California, Florida, Louisiana, New Jersey, North Carolina, and Pennsylvania) and 2 metropolitan areas (Atlanta, GA, and Detroit, MI) and enrolled in 1995-1996 (n = 196 905). Annual average PM2.5 concentrations were estimated for a 5-year historical period 10 years prior to enrollment (1980-1984). We used Cox regression to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between a 10 µg/m3 increase in PM2.5 and breast cancer incidence overall and by estrogen receptor status and catchment area. Results With follow-up of participants through 2017, a total of 15 870 breast cancer cases were identified. A 10 ug/m3 increase in PM2.5 was statistically significantly associated with overall breast cancer incidence (HR = 1.08, 95% CI = 1.02 to 1.13). The association was evident for estrogen receptor–positive (HR = 1.10, 95% CI = 1.04 to 1.17) but not estrogen receptor–negative tumors (HR = 0.97, 95% CI = 0.84 to 1.13; P heterogeneity = .3). Overall breast cancer hazard ratios were more than 1 across the catchment areas, ranging from a hazard ratio of 1.26 (95% CI = 0.96 to 1.64) for North Carolina to a hazard ratio of 1.04 (95% CI = 0.68 to 1.57) for Louisiana (P heterogeneity = .9). Conclusions In this large US cohort with historical air pollutant exposure estimates, PM2.5 was associated with risk of estrogen receptor–positive breast cancer. State-specific estimates were imprecise but suggest that future work should consider region-specific associations and the potential contribution of PM2.5 chemical constituency in modifying the observed association. [ABSTRACT FROM AUTHOR]

Background: Number of opiate users worldwide has doubled over the past decade, but not all of them are diagnosed with opioid use disorder. We aimed to identify the prevalence and risk factors for OUD after ten years of follow-up. Methods: Among 8,500 chronic opiate users at Golestan Cohort Study baseline (2004–2008), we recalled a random sample of 451 subjects in 2017. We used three questionnaires: a questionnaire about current opiate use including type and route of use, the drug use disorder section of the Composite International Diagnostic Interview lifetime version, and the validated Kessler10 questionnaire. We defined opioid use disorder and its severity based on the DSM-5 criteria and used a cutoff of 12 on Kessler10 questionnaire to define psychological distress. Results: Mean age was 61.2 ± 6.6 years (84.7% males) and 58% were diagnosed with opioid use disorder. Starting opiate use at an early age and living in underprivileged conditions were risk factors of opioid use disorder. Individuals with opioid use disorder were twice likely to have psychological distress (OR = 2.25; 95%CI: 1.44–3.52) than the users without it. In multivariate regression, former and current opiate dose and oral use of opiates were independently associated with opioid use disorder. Each ten gram per week increase in opiate dose during the study period almost tripled the odds of opioid use disorder (OR = 3.18; 95%CI: 1.79–5.63). Conclusions: Chronic opiate use led to clinical opioid use disorder in more than half of the users, and this disorder was associated with psychological distress, increasing its physical and mental burden in high-risk groups. [ABSTRACT FROM AUTHOR]

Background. Benzene is a known human carcinogen. Human exposure to benzene can be assessed by measuring trans, trans-muconic acid (MUCA) in urine. Golestan Province in northeastern Iran has been reported to have high incidence of esophageal cancer linked to the use of tobacco products. This manuscript evaluates the urinary MUCA concentrations among the participants of the Golestan Cohort Study (GCS). Methods. We analyzed MUCA concentration in 177 GCS participants' urine samples and performed nonparametric pairwise multiple comparisons to determine statistically significant difference among six different product use groups. Mixed effects model was fitted on 22 participants who exclusively smoked cigarette and 51 participants who were classified as nonusers. The urinary MUCA data were collected at the baseline and approximately five years later, and intraclass correlation coefficient (ICC) was calculated from the model. Results. Compared with nonusers, tobacco smoking was associated with higher urinary MUCA concentrations. Based on the nonparametric test of pairwise multiple comparisons, MUCA concentrations among participants who smoked combusted tobacco products were statistically significantly higher compared to nonusers. Urinary MUCA collected five years apart from the same individuals showed moderate reliability (ICC = 0.41), which was expected given the relatively short half-life (∼6 h) of MUCA. Conclusion. Our study revealed that tobacco smoke was positively associated with increased levels of urinary MUCA concentration, indicating that it is a significant source of benzene exposure among GCS participants. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Association between smoking and risk of bladder cancer among men and women," by N. D. Freedman and colleagues in a 2011 issue, along with the authors' reply.

Background: Online questionnaires are commonly used to collect information from participants in epidemiological studies. This requires building questionnaires using machine-readable formats that can be delivered to study participants using web-based technologies such as progressive web applications. However, the paucity of open-source markup standards with support for complex logic make collaborative development of web-based questionnaire modules difficult. This often prevents interoperability and reusability of questionnaire modules across epidemiological studies. Results: We developed an open-source markup language for presentation of questionnaire content and logic, Quest, within a real-time renderer that enables the user to test logic (e.g., skip patterns) and view the structure of data collection. We provide the Quest markup language, an in-browser markup rendering tool, questionnaire development tool and an example web application that embeds the renderer, developed for The Connect for Cancer Prevention Study. Conclusion: A markup language can specify both the content and logic of a questionnaire as plain text. Questionnaire markup, such as Quest, can become a standard format for storing questionnaires or sharing questionnaires across the web. Quest is a step towards generation of FAIR data in epidemiological studies by facilitating reusability of questionnaires and data interoperability using open-source tools. [ABSTRACT FROM AUTHOR]

Background We sought to develop a proteomics-based risk model for lung cancer and evaluate its risk-discriminatory performance in comparison with a smoking-based risk model (PLCOm2012) and a commercially available autoantibody biomarker test. Methods We designed a case-control study nested in 6 prospective cohorts, including 624 lung cancer participants who donated blood samples at most 3 years prior to lung cancer diagnosis and 624 smoking-matched cancer free participants who were assayed for 302 proteins. We used 470 case-control pairs from 4 cohorts to select proteins and train a protein-based risk model. We subsequently used 154 case-control pairs from 2 cohorts to compare the risk-discriminatory performance of the protein-based model with that of the Early Cancer Detection Test (EarlyCDT)-Lung and the PLCOm2012 model using receiver operating characteristics analysis and by estimating models' sensitivity. All tests were 2-sided. Results The area under the curve for the protein-based risk model in the validation sample was 0.75 (95% confidence interval [CI] = 0.70 to 0.81) compared with 0.64 (95% CI = 0.57 to 0.70) for the PLCOm2012 model (P difference =.001). The EarlyCDT-Lung had a sensitivity of 14% (95% CI = 8.2% to 19%) and a specificity of 86% (95% CI = 81% to 92%) for incident lung cancer. At the same specificity of 86%, the sensitivity for the protein-based risk model was estimated at 49% (95% CI = 41% to 57%) and 30% (95% CI = 23% to 37%) for the PLCOm2012 model. Conclusion Circulating proteins showed promise in predicting incident lung cancer and outperformed a standard risk prediction model and the commercialized EarlyCDT-Lung. [ABSTRACT FROM AUTHOR]