Lifetime dairy product consumption and breast cancer risk: a prospective cohort study by tumor subtypes.

BACKGROUND: Previous literature on dairy products and risk of breast cancer is inconsistent, and the relationship may depend on the life-period of dietary assessment. OBJECTIVE: We examined dairy consumption from adolescence through later adulthood and incidence of breast cancer by menopausal status and tumor molecular subtypes in the Nurses' Health Study (NHS), a prospective cohort study. METHODS: We analyzed data from 63,847 females in the NHS collected from 1980 to 2018. Average intake of dairy products during adulthood was assessed by validated semiquantitative food frequency questionnaires throughout follow-up. Participants recalled adolescent dietary intake in 1986. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HRs) relating dairy product consumption to breast cancer risk overall, by menopausal status, and by subtypes. RESULTS: We documented 5733 incident cases of invasive breast cancer during 32 y of follow-up (n = 5298 postmenopausal). Lifetime, adolescent, adulthood, and postmenopausal total dairy and milk intakes were not associated with overall breast cancer risk (nonsignificant HRs comparing highest with lowest quintile range = 0.97-1.08), although there was a suggestive positive association between adolescent milk intake and breast cancer risk (HR: 1.09; 95% CI: 1.00, 1.18). Higher lifetime and premenopausal cheese intakes were associated with modestly lower risks of breast cancer (comparing highest with lowest quintile, HR for lifetime cheese intake: 0.90; 95% CI: 0.82, 0.98; HR for premenopausal cheese intake: 0.89; 95% CI: 0.79, 1.00). Results varied by tumor subtype and some evidence for heterogeneity was observed for an association between premenopausal milk intake and breast cancer (HR for estrogen receptor [ER]-positive: 0.84; 95% CI: 0.72, 0.99; ER-negative: 1.36; 95% CI: 1.00, 1.84; P heterogeneity = 0.04). CONCLUSIONS: These findings suggest that overall dairy consumption was not associated with risk of breast cancer. However, heterogeneity was observed for type of dairy food, period of life, and tumor subtypes.

Different operationalizations of the 2018 WCRF/AICR cancer prevention recommendations and risk of cancer.

BACKGROUND: The standardized scoring system assessing adherence to the 2018 World Cancer Research Fund (WCRF)/American Institute for Cancer Research (AICR) cancer prevention recommendations assigns equal weight for each recommendation, thereby giving higher weight to dietary factors collectively (5 points) than adiposity (1 point) and physical activity (1 point). An alternative score assigning equal weights to the adiposity, physical activity, alcohol, and other dietary (composite) recommendations may better predict cancer associations. METHODS: We examined associations between standardized and alternative scores with cancer risk in two US prospective cohorts. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox regression. RESULTS: During 28 years of follow-up, 16,342 incident cancer cases in women and 8729 cases in men occurred. Individuals in the highest versus lowest quintile of the standardized score had a reduced overall cancer risk (women: HR = 0.89, 95% CI: 0.85, 0.94; men: HR = 0.87, 95% CI: 0.81, 0.94). Results were slightly stronger for the alternative score (women: HR = 0.83, 95% CI: 0.79, 0.87; men: HR = 0.81, 95% CI: 0.75, 0.86). Similar patterns were observed for obesity-related, alcohol-related, smoking-related, and digestive system cancers. CONCLUSIONS: Greater adherence to the WCRF/AICR cancer prevention recommendations was associated with lower cancer risk. A score assigning equal weights to the adiposity, physical activity, alcohol, and all remaining diet components yielded stronger associations than the standardized score.

In utero exposure to diethylstilbestrol and blood DNA methylation in adult women: Results from a meta-analysis of two cohort studies.

BACKGROUND: Prenatal exposure to diethylstilbestrol (DES) is associated with several adverse health outcomes. Animal studies have shown associations between prenatal DES exposure and DNA methylation. OBJECTIVE: The aim of this study was to explore blood DNA methylation in women exposed and unexposed to DES in utero. METHODS: Sixty women (40 exposed and 20 unexposed) in the National Cancer Institute's Combined DES Cohort Study and 199 women (99 exposed and 100 unexposed women) in the Sister Study Cohort were included in this analysis. Within each study, robust linear regression models were used to assess associations between DES exposure and blood DNA methylation. Study-specific associations were combined using fixed-effect meta-analysis with inverse variance weights. Our analysis focused on CpG sites located within nine candidate genes identified in animal models. We further explored whether in utero DES exposure was associated with age acceleration. RESULTS: Blood DNA methylation levels at 10 CpG sites in six of the nine candidate genes were statistically significantly associated with prenatal DES exposure (P < 0.05) in this meta-analysis. Genes included EGF, EMB, EGFR, WNT11, FOS, and TGFB1, which are related to cell proliferation and differentiation. The most statistically significant CpG site was cg19830739 in gene EGF, and it was associated with lower methylation levels in women prenatally exposed to DES compared with those not exposed (P < 0.0001; false discovery rate<0.05). The association between prenatal DES exposure in utero and age acceleration was not statistically significant (P = 0.07 for meta-analyzed results). CONCLUSIONS: There are few opportunities to investigate the effects of prenatal DES exposure. These findings suggest that in utero DES exposure may be associated with differential blood DNA methylation levels, which could mediate the increased risk of several adverse health outcomes observed in exposed women. Our findings need further evaluation using larger data sets.

Multipollutant, longitudinal analysis of the association between urinary tungsten and incident diabetes in a rural population.

BACKGROUND: Cross-sectional studies suggest tungsten (W) exposure may be associated with diabetes. We assessed longitudinal associations between urinary W and fasting glucose, 2-hour glucose, insulin resistance (HOMA-IR), ß-cell function (HOMA-ß), and incident type 2 diabetes. METHODS: We used data from 1,609 Hispanic and non-Hispanic White adults with 20 to 74 years of age residing in rural Colorado and participating in the San Luis Valley Diabetes Study. Urinary metal exposure values were measured at baseline and natural log-transformed. We assessed longitudinal associations between urinary W and continuous outcome measures using linear-mixed effect models and associations with incident diabetes using Fine and Gray competing risks regression models (competing event = all-cause mortality). The main adjustment set of covariates included: age, sex, ethnicity, education, smoking status, hypertension, body mass index, caloric intake, alcohol intake, and urinary creatinine levels. Secondary models were further adjusted for arsenic, cadmium, and lead exposures. We assessed whether sex or ethnicity were effect modifiers. RESULTS: At baseline, the median W concentration was 0.22 µg/L (interquartile range = 0.20, 0.59). In the main cross-sectional analyses, lnW levels were significantly associated with 3% higher lnHOMA-IR (95% CI = 1 to 5). In the main longitudinal models, lnW was significantly associated with 1% higher natural log-transformed fasting glucose (95% CI = <1 to 1), 3% higher natural log-transformed HOMA-IR (95% CI = 2 to 5), and 28% higher incident diabetes (subdistribution hazard ratio=1.28, 95% CI = 1.09 to 1.50). Results remained significant when further adjusting for other metals. We observed evidence for effect modification by sex and ethnicity. CONCLUSION: Urinary W was longitudinally associated with adverse metabolic health indicators.