Health Professionals Follow-up Study Cohorts Research Articles

Identification of Sweetness Preference-Related Single-Nucleotide Polymorphisms for Polygenic Risk Scores Associated with Obesity.

Our study aimed to identify sweetness preference-associated single-nucleotide polymorphisms (SNPs), characterize the related genetic loci, and develop SNP-based polygenic risk scores (PRS) to analyze their associations with obesity. For genotyping, we utilized a pooled genome-wide association study (GWAS) dataset of 18,499 females and 10,878 males. We conducted genome-wide association analyses, functional annotation, and employed the weighted method to calculate the levels of PRS from 677 sweetness preference-related SNPs. We used Cox proportional hazards modeling with time-varying covariates to estimate age-adjusted and multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) for obesity incidence. We also tested the correlation between PRS and environmental factors, including smoking and dietary components, on obesity. Our results showed that in males, the TT genotype of rs4861982 significantly increased obesity risk compared to the GG genotype in the Health Professionals Follow-up Study (HPFS) cohort (HR = 1.565; 95% CI, 1.122-2.184; p = 0.008) and in the pooled analysis (HR = 1.259; 95% CI, 1.030-1.540; p = 0.025). Protein tyrosine phosphatase receptor type O (PTPRO) was identified as strongly associated with sweetness preference, indicating a positive correlation between sweetness preference and obesity risk. Moreover, each 10 pack-year increment in smoking was significantly associated with an increased risk of obesity in the HPFS cohort (HR = 1.024; 95% CI, 1.000-1.048) in males but not in females. In conclusion, significant associations between rs4861982, sweetness preference, and obesity were identified, particularly among males, where environmental factors like smoking are also correlated with obesity risk.

Weight loss strategies, weight change, and type 2 diabetes in US health professionals: A cohort study.

BackgroundWeight loss is crucial for disease prevention among individuals with overweight or obesity. This study aimed to examine associations of weight loss strategies (WLSs) with weight change and type 2 diabetes (T2D) risk among US health professionals.Methods and findingsThis study included 93,110 participants (24 to 60 years old; 11.6% male) from the Nurses’ Health Study (NHS), NHSII, and Health Professionals Follow-Up Study (HPFS) cohorts who were free of T2D, cardiovascular disease, and cancer at baseline (1988 for NHS/HPFS and 1989 for NHSII) for analyses of weight change and 104,180 (24 to 78 years old; 14.2% male) for T2D risk assessment. WLSs used to achieve an intentional weight loss of 4.5+ kg were collected in 1992 (NHS/HPFS)/1993 (NHSII) and grouped into 7 mutually exclusive categories, including low-calorie diet, exercise, low-calorie diet and exercise, fasting, commercial weight loss program (CWLP), diet pills, and FCP (selected at least 2 methods from fasting, CWLP, and pill). The reference group was participants who did not attempt to lose weight. Generalized estimating equations and Cox regression were applied to estimate up to 10-year weight change trajectory and incident T2D risk through 2016 (NHS/HPFS)/2017 (NHSII), respectively.The associations of WLSs with weight change and T2D risk were differential by baseline body weight (Pinteraction < 0.01). Among individuals with obesity, all WLSs tended to associate with less weight gain [ranging from −4.2% (95% confidence interval (CI), −5.1% to −3.2%; P < 0.001) for exercise to −0.3% (−1.2% to 0.7%; P > 0.99) for FCP] and a lower T2D risk [hazard ratios (HRs) ranging from 0.79 (0.66 to 0.95; P = 0.04) for exercise to 0.87 (0.66 to 1.13; P = 0.30) for pill]. Such a pattern was less clear among overweight individuals: the difference of weight change varied from −2.5% (−3.0% to −2.1%; P < 0.001) for exercise to 2.0% (1.3% to 2.7%; P < 0.001) for FCP, and HRs of T2D varied from 0.91 (0.77 to 1.07; P = 0.29) for exercise to 1.42 (1.11 to 1.81; P = 0.02) for pill. The pattern was further inverted among lean individuals in that weight change ranged from −0.4% (−0.6% to −0.1%; P = 0.02) for exercise to 3.7% (3.1% to 4.3%; P < 0.001) for FCP, and the HRs of T2D ranged from 1.09 (0.91 to 1.30; P = 0.33) for exercise to 1.54 (1.13 to 2.10; P = 0.008) for pill. Approximately 15.6% to 46.8% of the association between WLSs and the T2D risk was attributed to weight changes. This study was limited by a single assessment of WLSs, heterogeneity within each WLS, and potential misclassification of the timing of weight loss and weight regain.ConclusionsThe current study showed that individuals with obesity who attempted to lose weight, regardless of the WLSs used, tended to gain less body weight and have a lower diabetes risk. In contrast, lean individuals who intentionally lost weight tended to gain more weight and have a higher diabetes risk. These data support the notion that intentional weight loss may not be beneficial for lean individuals and the use of WLSs for achieving weight loss shall be guided by medical indications only.

Abstract 027: Cumulative Consumption Of Sulfur Amino Acids And Risks Of Cardiovascular Disease And Mortality; Analysis Of Two Prospective Cohort Studies

Background: Preclinical studies suggested that high intakes of sulfur amino acids (SAA), including methionine and cysteine, may increase risk of age-related chronic diseases. Until now, no epidemiologic studies have investigated habitual dietary intake of SAA in relation to risk of cardiovascular disease (CVD) and mortality. Methods: We prospectively followed 120,699 participants in the Nurses’ Health Study (1984-2016) and Health Professionals Follow-up Study (1986-2016) cohorts who had no known history of cancer, CVD, or diabetes at baseline. Diet was assessed using a validated food frequency questionnaire that was updated every 2-4 years. Multivariable Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for CVD and all-cause and CVD mortality across quintiles of energy adjusted SAA intake. Results: During up to 32 years of follow up, we documented 13,547 incident CVD events and 33,958 deaths, of which 7637 were due to CVD. Participants on average consumed more than 2-fold the recommended daily allowance of SAA (19 mg/kg/day), and the main food sources included beef, chicken, and milk. After adjustment for non-dietary and dietary risk factors including total energy intake, higher SAA intake was significantly associated with higher risks of CVD, CVD mortality, and all-cause mortality in men and women. In the meta-analysis combining both cohorts, comparing participants in the highest quintile with those in the lowest quintile of SAA intake, HRs (95% CI) were 1.12 (1.05, 1.20) for CVD, 1.28 (1.11, 1.47) for CVD mortality, and 1.15 (1.11, 1.19) for all-cause mortality. These associations were similar across strata of age, body mass index, physical activity, ratio of animal to plant protein, smoking, and alcohol consumption (p interaction &gt; 0.05 for all), and they remained significant after further adjustment for total protein intake. Conclusions: Our data suggest that high SAA intake is associated with greater risks of CVD and mortality in men and women.

Body Mass Index and Mortality Among Adults With Incident Myocardial Infarction.

The relationship between body mass index (BMI; weight (kg)/height (m)2) and mortality among survivors of myocardial infarction (MI) remains controversial. We examined the relationships of BMI before and after MI and change in weight with all-cause mortality among participants in the Nurses' Health Study (1980-2016) and Health Professionals Follow-up Study (1988-2016) cohorts. During a follow-up period of up to 36 years, we documented 4,856 participants with incident nonfatal MI, among whom 2,407 died during follow-up. For pre-MI and post-MI BMI, overweight was not associated with lower mortality. Obesity (BMI≥30) was associated with higher risk of mortality. Compared with participants with post-MI BMI of 22.5-24.9, hazard ratios were 1.16 (95% confidence interval (CI): 1.01, 1.34) for BMI 30.0-34.9 and 1.52 (95% CI: 1.27, 1.83) for BMI≥35.0 (P for trend<0.001). Compared with stable weight from before MI to after MI, a reduction of more than4 BMI units was associated with increased mortality (hazard ratio=1.53, 95%: CI: 1.28, 1.83). This increase was seen only among participants who lost weight without improving their physical activity or diet. Our findings showed no survival benefit of excess adiposity in relation to risk of mortality. Weight loss from before to after MI without lifestyle improvement may reflect reverse causation and disease severity.

Categorising ultra-processed foods in large-scale cohort studies: evidence from the Nurses' Health Studies, the Health Professionals Follow-up Study, and the Growing Up Today Study.

This manuscript details the strategy employed for categorising food items based on their processing levels into the four NOVA groups. Semi-quantitative food frequency questionnaires (FFQs) from the Nurses' Health Studies (NHS) I and II, the Health Professionals Follow-up Study (HPFS) and the Growing Up Today Studies (GUTS) I and II cohorts were used. The four-stage approach included: (i) the creation of a complete food list from the FFQs; (ii) assignment of food items to a NOVA group by three researchers; (iii) checking for consensus in categorisation and shortlisting discordant food items; (iv) discussions with experts and use of additional resources (research dieticians, cohort-specific documents, online grocery store scans) to guide the final categorisation of the short-listed items. At stage 1, 205 and 315 food items were compiled from the NHS and HPFS, and the GUTS FFQs, respectively. Over 70% of food items from all cohorts were assigned to a NOVA group after stage 2. The remainder were shortlisted for further discussion (stage 3). After two rounds of reviews at stage 4, 95⋅6% of food items (NHS + HPFS) and 90⋅7% items (GUTS) were categorised. The remaining products were assigned to a non-ultra-processed food group (primary categorisation) and flagged for sensitivity analyses at which point they would be categorised as ultra-processed. Of all items in the food lists, 36⋅1% in the NHS and HPFS cohorts and 43⋅5% in the GUTS cohorts were identified as ultra-processed. Future work is needed to validate this approach. Documentation and discussions of alternative approaches for categorisation are encouraged.

Post-diagnosis dietary insulinemic potential and survival outcomes among colorectal cancer patients

BackgroundThe empirical dietary index for hyperinsulinemia (EDIH) score is a validated food-based dietary score that assesses the ability of whole-food diets to predict plasma c-peptide concentrations. Although the EDIH has been extensively applied and found to be predictive of risk of developing major chronic diseases, its influence on cancer survival has not been evaluated. We applied the EDIH score in a large cohort of colorectal cancer patients to assess the insulinemic potential of their dietary patterns after diagnosis and determine its influence on survival outcomes.MethodsWe calculated EDIH scores to assess the insulinemic potential of post-diagnosis dietary patterns and examined survival outcomes in a sample of 1718 stage I-III colorectal cancer patients in the Nurses’ Health Study and Health Professionals Follow-up Study cohorts. Multivariable-adjusted Cox regression was applied to compute hazard ratios (HR) and 95% confidence intervals (CI) for colorectal cancer-specific mortality and all-cause mortality. We also examined the influence of change in diet from pre- to post-diagnosis period, on mortality.ResultsDuring a median follow-up of 9.9 years, there were 1008 deaths, which included 272 colorectal cancer-specific deaths (27%). In the multivariable-adjusted analyses, colorectal cancer patients in the highest compared to lowest EDIH quintile, had a 66% greater risk of dying from colorectal cancer: HR, 1.66; 95% CI, 1.03, 2.69; and a 24% greater risk of all-cause death: HR, 1.24; 95%CI, 0.97, 1.58. Compared to patients who consumed low insulinemic diets from pre- to post-diagnosis period, patients who persistently consumed hyperinsulinemic diets were at higher risk of colorectal cancer death (HR,1.51; 95%CI, 0.98, 2.32) and all-cause death (HR, 1.31; 95%CI, 1.04, 2.64).ConclusionOur findings suggest that a hyperinsulinemic dietary pattern after diagnosis of colorectal cancer is associated with poorer survival. Interventions with dietary patterns to reduce insulinemic activity and impact survivorship are warranted.

Religious Services May Reduce Deaths of Despair

Religious Services May Reduce Deaths of Despair

Physical Activity and Mortality among Male Survivors of Myocardial Infarction.

An inverse association between physical activity (PA) and risk of CHD has been seen in many studies, but evidence for benefits of PA after myocardial infarction (MI) in reducing mortality is limited. Using data from the Health Professionals Follow-up Study cohort, we followed male survivors of MI. Short- and long-term changes in PA from before to after MI were calculated, and participants without ambulation impairment were classified into maintained low, decreased, increased, or maintained high PA categories. Cox models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for mortality across PA and PA change categories. During a mean of 14 yr of follow-up of 1651 incident nonfatal MI cases, we documented 678 deaths, 307 were due to cardiovascular disease. The adjusted HR for all-cause mortality comparing ≥21 with ≤1.5 MET·wk of PA before MI was 0.73 (95% CI = 0.59-0.89, Ptrend = 0.03). Compared with men who maintained low PA before and after MI, men who maintained high PA had a 39% (95% CI = 25-50) lower risk of all-cause mortality, and those who had a long-term increase in PA from before to after MI had a 27% (95% CI = 6-43) lower risk. Walking for ≥30 min·d after MI was associated with a 29% lower mortality (HR = 0.71, 95% CI = 0.58-0.84), independent of walking pace, and walking pace after MI was inversely associated with mortality (HR = 0.67, 95% CI = 0.49-0.92). Maintaining a high PA or having a long-term increase in PA from before to after MI was associated with lower mortality among male MI survivors. Walking time and walking pace after MI were each inversely associated with mortality.

Fish and marine fatty acids intakes, the FADS genotypes and long-term weight gain: a prospective cohort study

ObjectiveWe tested whether genetic variants near fatty acid desaturases gene (FADS) cluster, which were recently identified to be signatures of adaptation to fish-rich and n-3 polyunsaturated fatty acids (PUFAs)-rich diet,...

Gene-Environment Interactions and the Risk of Barrett's Esophagus in Three US Cohorts.

Several single-nucleotide polymorphisms (SNPs) have been associated with Barrett's esophagus (BE) risk. In addition, environmental factors including smoking, alcohol consumption, and heartburn increase BE risk. However, data on potential interactions between these genetic and environmental factors on BE risk are scant. Understanding how genes and environmental risk factors interact may provide key insight into the pathophysiology of BE, and potentially identify opportunities for targeted prevention and treatment. The objectives of this study were to examine the main effects and the potential effect modification between known genetic loci (SNPs) and established environmental risk factors for BE. We performed a nested case-control study using data on 401 incident BE cases and 436 age-matched controls from the Nurses' Health Study, Nurses' Health Study II, and Health Professionals Follow-up Study cohorts, who gave blood and completed biennial questionnaires. Overall, we genotyped 46 SNPs identified in previous BE genome-wide association studies as well as SNPs in candidate genes related to BE susceptibility (i.e., related to excess body fat, fat distribution, factors associated with insulin resistance, and inflammatory mediators). A genetic risk score (GRS) was constructed to evaluate the combined effect of the selected SNPs on BE risk. Interactions between SNPs and BE risk factors were also assessed. We observed a suggestive, but not statistically significant, association between our GRS and BE risk: a one-allele increase in the unweighted GRS increased the risk of BE by a factor of 1.20 (95% confidence interval = 1.00-1.44; P = 0.057). We did not observe any meaningful multiplicative interactions between smoking, alcohol consumption, or heartburn duration and BE genotypes. When we assessed the joint effect of weighted GRS and BE risk factors, we did not observe any significant interaction with alcohol and heartburn duration, whereas smoking showed a significant multiplicative interaction (P = 0.016). Our results suggest that SNPs associated with BE at genome-wide significant levels can be combined into a GRS with a potential positive association with BE risk.

Aspirin: Does it Have a Role for Chemoprevention of Hepatocellular Carcinoma?

Aspirin: Does it Have a Role for Chemoprevention of Hepatocellular Carcinoma?

Habitual consumption of long-chain n–3 PUFAs and fish attenuates genetically associated long-term weight gain

A growing amount of data suggests that n-3 (ω-3) polyunsaturated fatty acid (PUFA) intake may modify the genetic association with weight change. We aimed to prospectively test interactions of habitual consumption of n-3 PUFAs or fish, the major food source, with overall genetic susceptibility on long-term weight change. Gene-diet interactions were examined in 11,330 women from the Nurses' Health Study (NHS), 6773 men from the Health Professionals Follow-Up Study (HPFS), and 6254 women from the Women's Health Initiative (WHI). In the NHS and HPFS cohorts, food-sourced long-chain n-3 PUFA intake showed directionally consistent interactions with genetic risk score on long-term changes in BMI (P-interaction=0.01 in the HPFS, 0.15 in the NHS, and 0.01 in both cohorts combined). Such interactions were successfully replicated in the WHI, an independent cohort (P-interaction=0.02 in the WHI and 0.01 in the combined 3 cohorts). The genetic associations with changes in BMI (in kg/m2) consistently decreased (0.15, 0.10, 0.07, and -0.14 per 10 BMI-increasing alleles) across the quartiles of long-chain n-3 PUFAs in the combined cohorts. In addition, high fish intake also attenuated the genetic associations with long-term changes in BMI in the HPFS (P-interaction=0.01), NHS (P-interaction=0.03), WHI (P-interaction=0.10), and the combined cohorts (P-interaction=0.01); and the differences in BMI changes per 10 BMI-increasing alleles were 0.16, 0.06, -0.08, and -0.18, respectively, across the categories (≤1, 1∼4, 4∼6, and ≥7 servings/wk) of total fish intake. Similar interactions on body weight were observed for fish intake (P-interaction=0.003) and long-chain n-3 PUFA intake (P-interaction=0.12). Our study provides replicable evidence to show that high intakes of fish and long-chain n-3 PUFAs are associated with an attenuation of the genetic association with long-term weight gain based on results from 3 prospective cohorts of Caucasians.

Genetic and Epigenetic Determinants of Aggressiveness in Cribriform Carcinoma of the Prostate.

Among prostate cancers containing Gleason pattern 4, cribriform morphology is associated with unfavorable clinicopathologic factors, but its genetic features and association with long-term outcomes are incompletely understood. In this study, genetic, transcriptional, and epigenetic features of invasive cribriform carcinoma (ICC) tumors were compared with non-cribriform Gleason 4 (NC4) in The Cancer Genome Atlas (TCGA) cohort. ICC (n = 164) had distinctive molecular features when compared with NC4 (n = 102). These include: (i) increased somatic copy number variations (SCNV), specifically deletions at 6q, 8p and 10q, which encompassed PTEN and MAP3K7 losses and gains at 3q; (ii) increased SPOP mut and ATMmut ; (iii) enrichment for mTORC1 and MYC pathways by gene expression; and (iv) increased methylation of selected genes. In addition, when compared with the metastatic prostate cancer, ICC clustered more closely to metastatic prostate cancer than NC4. Validation in clinical cohorts and genomically annotated murine models confirmed the association with SPOPmut (n = 38) and PTENloss (n = 818). The association of ICC with lethal disease was evaluated in the Health Professionals Follow-up Study (HPFS) and Physicians' Health Study (PHS) prospective prostate cancer cohorts (median follow-up, 13.4 years; n = 818). Patients with ICC were more likely to develop lethal cancer [HR, 1.62; 95% confidence interval (CI), 1.05-2.49], independent from Gleason score (GS). IMPLICATIONS: ICC has a distinct molecular phenotype that resembles metastatic prostate cancer and is associated with progression to lethal disease.

Dietary Acrylamide Intake and Risk of Renal Cell Carcinoma in Two Large Prospective Cohorts.

Background: Accumulating evidence suggests that dietary acrylamide intake is not associated with the risk of most cancers in humans. However, a meta-analysis of five epidemiologic studies found a suggestion of an increased risk of kidney cancer with higher dietary acrylamide intake.Methods: We investigated this association in the prospective Health Professionals Follow-up Study (HPFS; 1986-2014) and Nurses' Health Study (NHS; 1980-2014) cohorts. Dietary acrylamide intake was calculated on the basis of 46 acrylamide-containing foods reported on food frequency questionnaires completed every 4 years. The associations with the incidence of total and fatal renal cell carcinoma (RCC; n = 292/84 HPFS, n = 337/87 NHS) during more than two decades of follow-up were assessed using Cox proportional hazards models adjusting for potential confounders.Results: There was no association between cumulative average or baseline acrylamide intake and the risk of total or fatal RCC risk in men or women. Acrylamide intake was also not associated with RCC risk among never-smokers, nor was it associated with the risk of clear cell RCC.Conclusions: Dietary acrylamide was not associated with risk of RCC in two long-term prospective cohorts with repeated measures of dietary intake.Impact: This analysis of RCC adds to the body of evidence that dietary acrylamide is not an important cancer risk factor in humans. Cancer Epidemiol Biomarkers Prev; 27(8); 979-82. ©2018 AACR.

Abstract NG03: Marine omega-3 polyunsaturated fatty acid and colorectal cancer prevention and treatment

Abstract NG03: Marine omega-3 polyunsaturated fatty acid and colorectal cancer prevention and treatment

Abstract 804: Gene-environment interactions and the risk of Barrett's esophagus in three US cohorts

Abstract Background: Several single nucleotide polymorphisms (SNPs) have been associated with Barrett's esophagus (BE) risk. Additionally, environmental factors including smoking, alcohol consumption and heartburn have been shown to increase BE risk. However, no studies have evaluated whether interactions between these genetic and environmental factors influence BE risk. Understanding how genes and environmental risk factors interact may provide key insight into the pathophysiology of BE. Objectives: To examine the main effects and the potential effect-modification between known genetic loci (SNPS) and established environmental risk factors for BE. Patients and Methods: We performed a nested case-control study using data on 401 incident BE cases and 436 age-matched controls from the Nurses’ Health Study, Nurses’ Health Study II, and Health Professionals Follow-up Study cohorts, who gave blood and completed biennial questionnaires. We genotyped SNPs identified in previous BE GWAS as well as SNPs in candidate genes related to BE susceptibility (i.e., related to excess body fat, fat distribution, factors associated with insulin resistance, and inflammatory mediators). A genetic risk score (GRS) was constructed to evaluate the combined effect of the selected SNPs on BE risk. Interactions between SNPs and BE risk factors were also assessed. Results and Conclusions: We found a borderline association between our GRS and BE risk: a one-allele increase in the unweighted GRS increased the risk of Barrett's esophagus by a factor of 1.20 (95%CI = 1.00-1.44; p = 0.057). We observed a significant interaction between smoking and BE genotypes (p-interaction = 0.016). However, while alcohol consumption and heartburn duration were strongly associated with BE, we did not observe any significant gene-environment interactions. Citation Format: Marta Crous-Bou, Diane Feskanich, Meir J. Stampfer, Charles S. Fuchs, Immaculata De Vivo, Brian C. Jacobson. Gene-environment interactions and the risk of Barrett's esophagus in three US cohorts. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 804.

Vitamin B2 intake and colorectal cancer risk; results from the Nurses' Health Study and the Health Professionals Follow-Up Study cohort.

Vitamin B2 serves as a cofactor to enhance one-carbon metabolism, maintain mucous membranes, and has been implicated in lowering colorectal cancer (CRC) risk. However, few prospective studies have examined the association between vitamin B2 intake and CRC. In this study, we estimated the associations between vitamin B2 intake and CRC risk using the Nurses' Health Study (NHS) and the Health Professionals Follow-Up Study (HPFS) cohorts. Vitamin B2 intake was measured by a validated food frequency questionnaire every 4 years. Among 100,033 women in the NHS and 44,007 men in the HPFS we documented a total of 3,037 incident CRC cases (2,093 women and 944 men) during 24-26 years of follow-up until 2010. Intakes of total (from food and supplements), dietary (from food only), and supplemental vitamin B2 were inversely related to CRC risk in age-adjusted analysis in NHS. However, the association was attenuated and no longer statistically significant in multivariate analysis (p-trend ≥0.08). The pooled multivariate relative risks (95% confidence interval) comparing individuals in the extreme quintiles of intakes were 0.93 (0.81-1.06) for total vitamin B2, 0.89 (0.61-1.28) for dietary vitamin B2 and 0.94 (0.81-1.08) for supplemental vitamin B2. These associations of total vitamin B2 intake were similar for risk of CRC with varying lag-time periods (0-4, 4-8, 8-12 or 12-16 years), for risk of CRC subtypes by tumor location, and across strata of intake of folate or alcohol. Our prospective data do not support a beneficial role of vitamin B2 intake in lowering incidence of CRC.

Population-wide Impact of Long-term Use of Aspirin and the Risk for Cancer.

The US Preventive Services Task Force recently recommended the use of aspirin to prevent colorectal cancer and cardiovascular disease among many US adults. However, the association of aspirin use with the risk for other cancer types and the potential population-wide effect of aspirin use on cancer, particularly within the context of screening, remain uncertain. To examine the potential benefits of aspirin use for overall and subtype-specific cancer prevention at a range of doses and durations of use and to estimate the absolute benefit of aspirin in the context of screening. Two large US prospective cohort studies, the Nurses' Health Study (1980-2010) and Health Professionals Follow-up Study (1986-2012), followed up 135 965 health care professionals (88 084 women and 47 881 men, respectively) who reported on aspirin use biennially. The women were aged 30 to 55 years at enrollment in 1976; the men, aged 40 to 75 years in 1986. Final follow-up was completed on June 30, 2012, for the Nurses' Health Study cohort and January 31, 2010, for the Health Professionals Follow-up Study cohort, and data were accessed from September 15, 2014, to December 17, 2015. Relative risks (RRs) for incident cancers and population-attributable risk (PAR). Among the 88 084 women and 47 881 men who underwent follow-up for as long as 32 years, 20 414 cancers among women and 7571 cancers among men were documented. Compared with nonregular use, regular aspirin use was associated with a lower risk for overall cancer (RR, 0.97; 95% CI, 0.94-0.99), which was primarily owing to a lower incidence of gastrointestinal tract cancers (RR, 0.85; 95% CI, 0.80-0.91), especially colorectal cancers (RR, 0.81; 95% CI, 0.75-0.88). The benefit of aspirin on gastrointestinal tract cancers appeared evident with the use of at least 0.5 to 1.5 standard aspirin tablets per week; the minimum duration of regular use associated with a lower risk was 6 years. Among individuals older than 50 years, regular aspirin use could prevent 33 colorectal cancers per 100 000 person-years (PAR, 17.0%) among those who had not undergone a lower endoscopy and 18 colorectal cancers per 100 000 person-years (PAR, 8.5%) among those who had. Regular aspirin use was not associated with the risk for breast, advanced prostate, or lung cancer. Long-term aspirin use was associated with a modest but significantly reduced risk for overall cancer, especially gastrointestinal tract tumors. Regular aspirin use may prevent a substantial proportion of colorectal cancers and complement the benefits of screening.

Association of Prostate Cancer Risk Variants with TMPRSS2:ERG Status: Evidence for Distinct Molecular Subtypes.

Numerous genetic variants have been confirmed as prostate cancer risk factors. These variants may confer susceptibility to the development of specific molecular alterations during tumor initiation and progression. The TMPRSS2:ERG gene fusion occurs in roughly 50% of prostate cancers. Genetic risk variants may influence the development of this fusion. We sought to determine whether prostate cancer risk variants are differentially associated with TMPRSS2:ERG fusion-positive and negative cancer. In the Health Professionals Follow-up Study and Physicians' Health Study Tumor Cohort, we evaluated the associations of 39 prostate cancer risk SNPs with TMPRSS2:ERG fusion status, measured by ERG protein expression. Logistic regression was performed to generate OR and 95% confidence intervals. The primary outcome was ERG(+) (n = 227) versus ERG(-) (n = 260) prostate cancer. A secondary outcome was ERG(+) or ERG(-) cancer versus controls without cancer. Six of 39 SNPs were significantly associated (P < 0.05) with ERG(+) versus ERG(-) disease. Three SNPs were exclusively associated with the risk of ERG(+), one with risk of ERG(-), and two with associations trending in opposite directions for ERG(+) and ERG(-) Only two significant SNPs would be expected by chance. Prostate cancer genetic risk variants are differentially associated with the development of ERG(+) and ERG(-) prostate cancer. Our findings suggest the molecular process of prostate carcinogenesis may be distinct for men with different underlying genetic predisposition. When examining risk factors for prostate cancer, the integration of molecular subtypes may enhance understanding of the etiology of this disease. Cancer Epidemiol Biomarkers Prev; 25(5); 745-9. ©2016 AACR.

A Prospective Analysis of Meat Mutagens and Colorectal Cancer in the Nurses' Health Study and Health Professionals Follow-up Study.

Background:Heterocyclic amines (HCAs) in cooked meats may play a role in colorectal cancer (CRC) development.Objectives:We aimed to prospectively examine the association between estimated intakes of HCAs and meat-derived mutagenicity (MDM) in two cohorts of health professionals, the Health Professionals Follow-up Study (HPFS) and the Nurses’ Health Study (NHS).Methods:In 29,615 men and 65,875 women, intake of the HCAs 2-amino-3,8-dimethylimidazo(4,5-j)quinoxaline (MeIQx), 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP), 2-amino-3,4,8-trimethylimidazo(4,5-f)quinoxaline (DiMeIQx), and MDM was estimated using a 1996 cooking questionnaire, the 1994 food frequency questionnaire, and an online database. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) and to adjust for potential confounders. Estimates for both cohorts were pooled using random-effects meta-analysis.Results:Between 1996 and 2010, 418 male and 790 female CRC cases were identified. Meat mutagen intake was not statistically significantly associated with risk of CRC [highest vs. lowest quintile, pooled HR (95% CI) for MeIQx: 1.12 (0.93, 1.34), p for trend 0.23; PhIP: 1.10 (0.90, 1.33), p for trend 0.35; MDM: 1.03 (0.86, 1.24), p for trend 0.75] or subtypes of CRC defined by tumor location (proximal or distal colon, or rectum). When analyzed by source of meat, PhIP from red but not from white meat was nonsignificantly positively associated with CRC and significantly positively associated with proximal cancers [HR (95% CI) per standard deviation increase of log-transformed intake: PhIP red meat: CRC: 1.06 (0.99, 1.12), proximal: 1.11 (1.02, 1.21); PhIP white meat: CRC: 0.99 (0.94, 1.04), proximal: 1.00 (0.93, 1.09)].Conclusions:Estimated intakes of meat mutagens were not significantly associated with CRC risk over 14 years of follow-up in the NHS and HPFS cohorts. Results for PhIP from red but not from white meat warrant further investigation.Citation:Le NT, Michels FA, Song M, Zhang X, Bernstein AM, Giovannucci EL, Fuchs CS, Ogino S, Chan AT, Sinha R, Willett WC, Wu K. 2016. A prospective analysis of meat mutagens and colorectal cancer in the Nurses’ Health Study and Health Professionals Follow-up Study. Environ Health Perspect 124:1529–1536; http://dx.doi.org/10.1289/EHP238