Association between physical activity changes and risk of incident ischemic stroke following cancer diagnosis: A nationwide retrospective cohort study.

BACKGROUND: Physical inactivity is prevalent after cancer treatment, which could increase ischemic stroke risk in cancer survivors. This study investigated the association between physical activity change from pre- to post-diagnosis and ischemic stroke risk among cancer survivors. METHODS: Using data from the Korean National Health Insurance Service database, 269,943 cancer survivors (mean [SD] age, 56.3 [12.1] years; 45.7% male) with no history of cardiovascular disease were evaluated based on changes in physical activity from pre- to post-diagnosis. Using the Fine-Gray model, subdistribution hazard ratios (sHRs) and 95% confidence intervals (CIs) for ischemic stroke risk were calculated, considering death as a competing risk. RESULTS: After cancer diagnosis, 62.0% remained inactive, 10.1% remained active, 16.6% became active, and 11.4% became inactive. During a mean (SD) follow-up of 4.1 (2.0) years, being active both pre- and post-diagnosis was associated with a 15% decreased risk of ischemic stroke (sHR, 0.85; 95% CI, 0.75-0.96), compared with those who remained inactive. Cancer survivors who became active and inactive post-diagnosis showed a 16% and 11% lower ischemic stroke risk (sHR, 0.84; 95% CI, 0.75-0.93; sHR, 0.89; 95% CI, 0.79-0.99), respectively, than those who remained inactive. Analysis by the primary cancer site did not substantially differ from the main findings. CONCLUSIONS: Physical activity is associated with reduced ischemic stroke risk among cancer survivors. The potential benefits of physical activity are not limited to individuals who were physically active before cancer diagnosis, thus preventive strategies against ischemic stroke should emphasize physical activity throughout the cancer journey.

Changes in physical activity and diabetes risk after cancer diagnosis: a nationwide cohort study.

PURPOSE: Physical activity has the potential to reduce the risk of diabetes after cancer diagnosis. However, current evidence supporting its effects is limited. This study aims to examine the associations between changes in physical activity and subsequent risk of diabetes among cancer survivors. METHODS: A total of 264,250 cancer survivors (mean age 56.7 (12.5) years, 44.2% males) without a prior history of diabetes were assessed for adherence to physical activity both before and after their diagnosis. The primary outcome was incident diabetes. The Fine-Gray proportional sub-distribution hazards model was used to calculate sub-distribution hazard ratios (sHRs) and 95% confidence intervals (CIs) for diabetes risk, considering death as a competing risk. RESULTS: Over a follow-up of 1,065,802 person-years, maintaining regular physical activity from pre-diagnosis was associated with a 10% reduced risk of diabetes after cancer diagnosis (sHR 0.90, 95% CI 0.85-0.96), considering traditional diabetes risk factors, sociodemographics, and primary cancer sites. Cancer survivors who became active and inactive after their cancer diagnosis exhibited a marginally decreased risk of diabetes (sHR 0.98, 95% CI 0.93-1.03; sHR 0.97, 95% CI 0.92-1.03). The strength and direction of the association varied depending on the primary site of cancer. CONCLUSIONS: Regular physical activity starting before a cancer diagnosis is associated with a lower risk of diabetes following the diagnosis, independent of established diabetes risk factors. IMPLICATIONS FOR CANCER SURVIVORS: The study underscores the importance of engaging in sufficient physical activity to mitigate the risk of diabetes in cancer survivors.

Income variability and incident cardiovascular disease in diabetes: a population-based cohort study.

BACKGROUND AND AIMS: Longitudinal change in income is crucial in explaining cardiovascular health inequalities. However, there is limited evidence for cardiovascular disease (CVD) risk associated with income dynamics over time among individuals with type 2 diabetes (T2D). METHODS: Using a nationally representative sample from the Korean National Health Insurance Service database, 1 528 108 adults aged 30-64 with T2D and no history of CVD were included from 2009 to 2012 (mean follow-up of 7.3 years). Using monthly health insurance premium information, income levels were assessed annually for the baseline year and the four preceding years. Income variability was defined as the intraindividual standard deviation of the percent change in income over 5 years. The primary outcome was a composite event of incident fatal and nonfatal CVD (myocardial infarction, heart failure, and stroke) using insurance claims. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated after adjusting for potential confounders. RESULTS: High-income variability was associated with increased CVD risk (HRhighest vs. lowest quartile 1.25, 95% CI 1.22-1.27; Ptrend < .001). Individuals who experienced an income decline (4 years ago vs. baseline) had increased CVD risk, which was particularly notable when the income decreased to the lowest level (i.e. Medical Aid beneficiaries), regardless of their initial income status. Sustained low income (i.e. lowest income quartile) over 5 years was associated with increased CVD risk (HRn = 5 years vs. n = 0 years 1.38, 95% CI 1.35-1.41; Ptrend < .0001), whereas sustained high income (i.e. highest income quartile) was associated with decreased CVD risk (HRn = 5 years vs. n = 0 years 0.71, 95% CI 0.70-0.72; Ptrend < .0001). Sensitivity analyses, exploring potential mediators, such as lifestyle-related factors and obesity, supported the main results. CONCLUSIONS: Higher income variability, income declines, and sustained low income were associated with increased CVD risk. Our findings highlight the need to better understand the mechanisms by which income dynamics impact CVD risk among individuals with T2D.

Mid- and long-term risk of atrial fibrillation among breast cancer surgery survivors.

BACKGROUND: The risk of incident atrial fibrillation (AF) among breast cancer survivors, especially for younger women, and cancer treatment effects on the association remain unclear. This study aimed to investigate the risk of AF among breast cancer survivors and evaluate the association by age group, length of follow-up, and cancer treatment. METHODS: Using data from the Korean Health Insurance Service database (2010-2017), 113,232 women newly diagnosed with breast cancer (aged ≥ 18 years) without prior AF history who underwent breast cancer surgery were individually matched 1:5 by birth year to a sample female population without cancer (n = 566,160) (mean[SD] follow-up, 5.1[2.1] years). Sub-distribution hazard ratios (sHRs) and 95% confidence intervals (CIs) considering death as a competing risk were estimated, adjusting for sociodemographic factors and cardiovascular/non-cardiovascular comorbidities. RESULTS: BCS had a slightly increased AF risk compared to their cancer-free counterparts (sHR 1.06; 95% CI 1.00-1.13), but the association disappeared over time. Younger BCS (age < 40 years) had more than a 2-fold increase in AF risk (sHR 2.79; 95% CI 1.98-3.94), with the association remaining similar over 5 years of follow-up. The increased risk was not observed among older BCS, especially those aged > 65 years. Use of anthracyclines was associated with increased AF risk among BCS (sHR 1.57; 95% CI 1.28-1.92), which was more robust in younger BCS (sHR 1.94; 95% CI 1.40-2.69 in those aged ≤ 50 years). CONCLUSIONS: Our findings suggest that younger BCS had an elevated risk of incident AF, regardless of the length of follow-up. Use of anthracyclines may be associated with increased mid-to-long-term AF risk among BCS.

Association between healthy dietary patterns and markers of oxidative stress in the Sister Study.

PURPOSE: We assessed the cross-sectional association between healthy dietary patterns [alternate Mediterranean diet (aMED), Dietary Approaches to Stop Hypertension (DASH), alternative Healthy Eating Index (aHEI), and Healthy Eating Index 2015 (HEI-2015)] and urinary biomarkers of oxidative stress. METHODS: Between 2003 and 2009, the Sister Study enrolled 50,884 breast cancer-free US women aged 35 to 74 (non-Hispanic White, 83.7%). Data were analyzed for 844 premenopausal and 454 postmenopausal women who had urine samples analyzed for F2-isoprostanes and non-missing covariate data. Food frequency questionnaire responses were used to calculate dietary pattern scores. Concentrations of 8-iso-prostaglandin F2α (8-iso-PGF2α) and its metabolite (8-iso-PGF2α-M) were measured in urine samples by GC/MS for premenopausal women and LC/MS for postmenopausal women. Multivariable linear regression models were used to estimate associations between aMED, DASH, aHEI, and HEI-2015 and urinary F2-isoprostanes by menopausal status. Effect modification by sociodemographic, lifestyle, and clinical characteristics was also evaluated. RESULTS: Among premenopausal women, the four dietary indices were inversely associated with 8-iso-PGF2α (aMED ßQ4vsQ1: - 0.17, 95% CI - 0.27, - 0.08; DASH ßQ4vsQ1: - 0.18, 95% CI - 0.28, - 0.08; aHEI ßQ4vsQ1: - 0.20, 95% CI - 0.30, - 0.10; HEI-2015 ßQ4vsQ1: - 0.19, 95% CI - 0.29, - 0.10). In contrast, inverse associations with 8-iso-PGF2α-M were found for the continuous aMED, aHEI, and HEI-2015. Associations between dietary indices and 8-iso-PGF2α were generally stronger among younger women, women with lower income, and women with higher BMI. Similar results were observed among postmenopausal women, though only the continuous DASH and aHEI models were statistically significant. CONCLUSION: Healthy dietary patterns were associated with lower levels of oxidative stress.

Dietary patterns, socioeconomic disparities, and risk of type 2 diabetes in the Sister Study.

AIMS: We investigated the role of socioeconomic disparities in the association between diet and risk of type 2 diabetes (T2D). METHODS: We used prospective data from 40,243 Sister Study participants aged 35 to 74 years who were enrolled in 2003-2009. Scores for healthy eating indices (alternate Mediterranean diet, Dietary Approaches to Stop Hypertension, alternative Healthy Eating Index, and Healthy Eating Index 2015 (HEI-2015)) were calculated using data from a 110-item food frequency questionnaire completed at enrollment. Incident T2D was defined based on self-reported physician's diagnosis or use of anti-diabetic medications. Multivariable-adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. RESULTS: We observed inverse associations between all four dietary indices and incident T2D after multivariable adjustment. These associations were most pronounced among women with higher educational attainment, higher income, and lower area deprivation index (ADI) (e.g., for the HEI-2015: low ADI, aHRQ4vsQ1: 0.44, 95% CI: 0.35, 0.56 vs high ADI, aHRQ4vsQ1: 0.75, 95% CI: 0.63, 0.90; pinteraction: 0.0007). CONCLUSIONS: Weaker associations among women with lower socioeconomic status and higher neighborhood deprivation suggests that other factors play a larger role in T2D incidence than diet quality among individuals with low SES.

Inflammatory potential of diet and risk of mortality in normal-weight adults with central obesity.

BACKGROUND & AIMS: Inflammatory potential of diet may contribute to poor health outcomes in individuals with metabolic disorders. In a representative sample of the U.S. population, we investigated the association between consuming a pro-inflammatory diet and mortality risk in adults with normal range of body mass index (BMI) but with central obesity. METHODS: This prospective cohort study included 3521 adults 20-90 years of age with normal BMI who participated in the National Health and Nutrition Examination Survey III, 1988-1994 and did not have a history of cardiovascular disease (CVD) or cancer and did not change their dietary intake in the year preceding baseline measurements. Mortality from all causes, CVD, and cancer was ascertained from the National Death Index. Normal-weight central obesity (NWCO, n = 1777) was defined as those with BMI 18.5 to <25 kg/m2 and waist-to-hip ratio (WHR) ≥0.85 in women and ≥0.90 in men. Severe central obesity was defined as WHR ≥0.92 in women and ≥1.00 in men. The dietary inflammatory index (DII®) was computed based on baseline dietary intake using 24-h dietary recalls, and associations with mortality were estimated using multivariable Cox proportional hazards regression. RESULTS: In individuals with NWCO, DII score (i.e., more pro-inflammatory diet) was associated with increased risk of CVD mortality (HRT3 vs T1, 1.89 [95% CI, 1.01-3.53], P trend = 0.04; HR 1 SD increase 1.29 [95% CI, 1.06-1.57]). This association was stronger with more severe central obesity (HRT3 vs T1, 2.79 [95% CI, 1.10-7.03], P trend = 0.03; HR 1 SD increase 1.52 [95% CI, 1.05-2.21]). DII score was not associated with increased risk of mortality in normal-weight individuals without central obesity or with risk of cancer mortality in either group. CONCLUSION: Among individuals in the normal-weight range of BMI, a pro-inflammatory diet assessed by high DII scores was associated with increased risk of CVD mortality in those with central obesity.

Association of dietary and plasma carotenoids with urinary F2-isoprostanes.

PURPOSE: Carotenoids may protect against chronic diseases including cancer and cardiometabolic disease by mitigating oxidative stress and/or inflammation. We cross-sectionally evaluated associations between carotenoids and biomarkers of oxidative stress or inflammation. METHODS: From 2003 to 2009, the Sister Study enrolled 50,884 breast cancer-free US women aged 35-74. Post-menopausal participants (n = 512) were randomly sampled to measure carotenoids and biomarkers of oxidative stress. Dietary carotenoid consumption was assessed using a validated 110-item Block 1998 food frequency questionnaire; use of ß-carotene-containing supplements was also assessed. Plasma carotenoids were quantified, adjusting for batch. Urinary markers of lipid peroxidation, 8-iso-prostaglandin F2α (8-iso-PGF2α) and its metabolite (8-iso-PGF2α-M) were also measured. Since the biomarker 8-iso-PGF2α can reflect both oxidative stress and inflammation, we used a modeled 8-iso-PGF2α to prostaglandin F2α ratio approach to distinguish effects reflecting oxidative stress versus inflammation. Multivariable linear regression was used to assess the associations of dietary and plasma carotenoids with the estimated biomarker concentrations. RESULTS: Total plasma carotenoids were inversely associated with 8-iso-PGF2α-M concentrations (P for trend across quartiles = 0.009). Inverse trends associations were also seen for α-carotene and ß-carotene. In contrast, lutein/zeaxanthin showed associations with both 8-iso-PGF2α and 8-iso-PGF2α-M concentrations. The inverse association for total carotenoids appeared to be specific for oxidative stress (chemical 8-iso-PGF2α; Phighest vs. lowest quartile = 0.04 and P for trend across quartiles = 0.02). The pattern was similar for α-carotene. However, lutein/zeaxanthin tended to have a stronger association with enzymatic 8-iso-PGF2α, suggesting an additional anti-inflammatory effect. Supplemental ß-carotene was inversely associated with both 8-iso-PGF2α and 8-iso-PGF2α-M concentrations, as well as with both chemical and enzymatic 8-iso-PGF2α. Dietary carotenoids were not associated with either biomarker. CONCLUSION: Plasma carotenoids and supplemental ß-carotene were associated with lower concentrations of 8-iso-PGF2α metabolite. Plasma carotenoids associations may reflect antioxidant effects.

Persistence of Risk for Type 2 Diabetes After Gestational Diabetes Mellitus.

OBJECTIVE: Gestational diabetes mellitus complicates ∼6% of pregnancies and strongly predicts subsequent type 2 diabetes. It has not been fully elucidated how risk depends on the number of affected pregnancies or how long the excess risk persists. RESEARCH DESIGN AND METHODS: We assessed reproductive histories in relation to risk of type 2 diabetes using a nationwide cohort of 50,884 women. Among participants who initially did not have diabetes, 3,370 were diagnosed with diabetes during 10 years of follow-up. We used Cox proportional hazards models that allowed risk to depend on age, cumulative number of pregnancies with gestational diabetes mellitus, and time since the most recent affected pregnancy, adjusting for BMI, educational level, and race/ethnicity. RESULTS: History of one or more pregnancies with gestational diabetes mellitus predicted elevated age-specific risk of type 2 diabetes, with a hazard ratio of 3.87 (95% CI 2.60-5.75) 6-15 years after an affected pregnancy. Risk increased steeply with multiple affected pregnancies. The age-specific associations attenuated over time after an affected pregnancy, with an estimated 24% reduction of the hazard ratio per decade. Risk remained elevated, however, for >35 years. CONCLUSIONS: Gestational diabetes mellitus predicted markedly increased rates of type 2 diabetes. Relative risk increased substantially with each additional affected pregnancy. The estimated hazard ratio declined with time after a pregnancy with gestational diabetes mellitus but remained elevated for >35 years. Women recalling a history of gestational diabetes mellitus should be screened regularly for type 2 diabetes, even late in life.

Healthy eating patterns and epigenetic measures of biological age.

BACKGROUND: Healthy eating is associated with lower risks of disease and mortality, but the mechanisms underlying these associations are unclear. Age is strongly related to health outcomes, and biological age can be estimated using the blood methylome. OBJECTIVES: To determine whether healthy eating patterns are associated with methylation-based measures of biological age. METHODS: Among women in the Sister Study, we calculated scores on 4 recommendation-based healthy eating indexes [Dietary Approaches to Stop Hypertension diet, Healthy Eating Index-2015, Alternative Healthy Eating Index (aHEI-2010), and the Alternative Mediterranean diet] using a validated 110-item Block FFQ completed at enrollment. Genome-wide DNA methylation data were generated using the HumanMethylation450 BeadChip on whole blood samples collected at enrollment from a case-cohort sample of 2694 women and were used to calculate 4 measures of epigenetic age acceleration (Hannum AgeAccel, Horvath AgeAccel, PhenoAgeAccel, and GrimAgeAccel). Linear regression models, adjusted for covariates and cohort sampling weights, were used to examine cross-sectional associations between eating patterns and measures of biological age. RESULTS: All 4 healthy eating indexes had inverse associations with epigenetic age acceleration, most notably with PhenoAgeAccel and GrimAgeAccel. Of these, the strongest associations were for aHEI-2010 [per 1-SD increase in diet quality, PhenoAgeAccel ß = -0.5 y (95% CI: -0.8 to -0.2 y) and GrimAgeAccel ß = -0.4 y (95% CI: -0.6 to -0.3 y)]. Although effect modification was not observed for most lifestyle factors, in analyses stratified by physical activity, the benefits of a healthy diet on epigenetic age acceleration were more pronounced among women who did not meet physical activity guidelines (reporting <2.5 h/wk of exercise). CONCLUSIONS: Higher diet quality is inversely associated with methylation-based measures of biological age. Improving diet could have the most benefits in lowering biological age among women with lower levels of physical activity. This trial was registered at clinicaltrials.gov as NCT00047970.

A prospective study of multiple sleep dimensions and hypertension risk among white, black and Hispanic/Latina women: findings from the Sister Study.

BACKGROUND: Poor sleep is associated with increased hypertension risk, but few studies have evaluated multiple sleep dimensions or investigated racial/ethnic disparities in this association among women. METHOD: We investigated multiple sleep dimensions (sleep duration, inconsistent weekly sleep patterns, sleep debt, frequent napping and difficulty falling or staying asleep) and hypertension risk among women, and determined modification by age, race/ethnicity and menopausal status. We used data from the Sister Study, a national cohort of 50 884 women who had sisters diagnosed with breast cancer in the United States enrolled in 2003-2009 and followed through September 2018. RESULTS: Of 33 497 women without diagnosed hypertension at baseline (mean age ±â€Šstandard deviation: 53.9 ±â€Š8.8 years; 88.7% White, 6.4% Black and 4.9% Hispanic/Latina), 23% (n = 7686) developed hypertension over a median follow-up of 10.1 years [interquartile range: 8.2-11.9 years]. Very short, short or long sleep duration, inconsistent weekly sleep patterns, sleep debt, frequent napping, insomnia, insomnia symptoms as well as short sleep and exploratory cumulative poor sleep score were associated with incident hypertension after adjustment for demographics factors. After additional adjustment for lifestyle and clinical factors, insomnia [hazard ratio = 1.09, 95% confidence interval (95% CI): 1.03-1.15] and insomnia symptoms plus short sleep (hazard ratio = 1.13, 95% CI: 1.05-1.21) remained associated with incident hypertension. These associations were stronger in younger (age<54 vs. ≥54 years) and premenopausal vs. postmenopausal women (all P-interaction < 0.05). Associations did not differ by race/ethnicity (all P-interaction > 0.05). CONCLUSION: Thus, screening for multiple sleep dimensions and prioritizing younger and premenopausal women may help identify individuals at high risk for hypertension.

Making sense of associations between type 2 diabetes, metformin, and breast cancer risk.

The relationship between type 2 diabetes (T2D), metformin, and breast cancer is complex. T2D may increase risk, but metformin used as first-line treatment of T2D may decrease breast cancer risk. This comment explores efforts to disentangle effects of T2D and metformin use on breast cancer risk in a prospective study.

Dietary inflammatory potential, oxidative balance score, and risk of breast cancer: Findings from the Sister Study.

Diet, inflammation, and oxidative stress may be important in breast carcinogenesis, but evidence on the role of the inflammatory and prooxidative potential of dietary patterns is limited. Energy adjusted-Dietary Inflammatory Index (E-DII™) and dietary oxidative balance score (D-OBS) were calculated for 43 563 Sister Study cohort participants who completed a Block 1998 food frequency questionnaire at enrollment in 2003-2009 and satisfied eligibility criteria. D-OBS was validated using measured F2 -isoprostanes and metabolites. High E-DII score and low D-OBS represent a more proinflammatory and prooxidant diet, respectively, and associations of quartiles of each index with breast cancer (BC) risk were estimated using multivariable Cox proportional hazards regression. There were 2619 BCs diagnosed at least 1 year after enrollment (mean follow-up 8.4 years). There was no overall association between E-DII and BC risk, whereas there was a suggestive inverse association for the highest vs lowest quartile of D-OBS (HR 0.92 [95% CI, 0.81-1.03]). The highest quartile of E-DII was associated with risk of triple-negative BC (HR 1.53 [95% CI, 0.99-2.35]). When the two indices were combined, a proinflammatory/prooxidant diet (highest tertile of E-DII and lowest tertile of D-OBS) was associated with increased risk for all BC (HR 1.13 [95% CI, 1.00-1.27]) and for triple-negative BC (1.72 [95% CI, 1.10-2.70]), compared to an antiinflammatory/antioxidant diet (lowest tertile of E-DII and highest tertile of D-OBS). Diets with increased inflammatory potential and reduced oxidative balance were positively associated with overall and triple-negative BC.

Association between meat consumption and risk of breast cancer: Findings from the Sister Study.

Meat consumption has been postulated to increase the risk of breast cancer, but this association has not been consistently seen. We examined the association between consumption of different types of meat, meat mutagens and incident invasive breast cancer. Information on consumption of different meat categories and meat cooking practice behaviors was obtained from 42,012 Sister Study participants who completed a Block 1998 Food Frequency Questionnaire at enrollment (2003-2009) and satisfied eligibility criteria. Exposure to meat type and meat mutagens was calculated, and associations with invasive breast cancer risk were estimated using multivariable Cox proportional hazards regression. During follow-up (mean, 7.6 years), 1,536 invasive breast cancers were diagnosed at least 1 year after enrollment. Increasing consumption of red meat was associated with increased risk of invasive breast cancer (HRhighest vs. lowest quartile :1.23, 95% CI: 1.02-1.48, ptrend = 0.01). Conversely, increasing consumption of poultry was associated with decreased invasive breast cancer risk (HR highest vs. lowest quartile : 0.85; 95% CI: 0.72-1.00; ptrend = 0.03). In a substitution model with combined red meat and poultry consumption held constant, substituting poultry for red meat was associated with decreased invasive breast cancer risk (HR highest vs. lowest quartile of poultry consumption: 0.72, 95% CI: 0.58-0.89). No associations were observed for cooking practices, estimated heterocyclic amines or heme iron from red meat consumption with breast cancer risk. Red meat consumption may increase the risk of invasive breast cancer, whereas poultry consumption may be associated with reduced risk. Substituting poultry for red meat could reduce breast cancer risk.

A Prospective Analysis of Red and Processed Meat Consumption and Risk of Colorectal Cancer in Women.

BACKGROUND: Red and processed meats have been implicated as risk factors in the development of colorectal cancer in U.S. women, but associations with cooking practices are less well established. METHODS: Data are from the Sister Study, a cohort of women ages 35 to 74 years from the United States and Puerto Rico who have a sister diagnosed with breast cancer. Red and processed meat consumption, meat cooking practices, and intake of common meat products were collected at baseline using self-administered questionnaires (N = 48,704). Multivariable HRs (HRadj) and 95% confidence intervals (95% CI) were estimated. RESULTS: During a median 8.7 years' follow-up (range <1-12.7 years), 216 colorectal cancer cases were diagnosed. In categorical analyses, an increased risk of colorectal cancer was seen in the highest quartile of processed meat consumption compared with the lowest [HRadj = 1.52 (95% CI, 1.01-2.30); P trend = 0.02], and for specific meat products, including breakfast sausages [HRadj = 1.85 (95% CI, 1.30-2.64)] and bacon [HRadj = 1.46 (95% CI, 1.01-2.11)]. The HRadj for the highest quartile of red meat consumption was 1.04 (95% CI, 0.68-1.60), and little evidence of association was observed for cooking practices or doneness of red meat. We observed positive associations with specific red meat products when cooking methods were considered, for example, grilled/barbequed steaks [HRadj = 2.23 (95% CI, 1.20-4.14)] and hamburgers [HRadj = 1.98 (95% CI, 1.00-3.91)]. CONCLUSIONS: Higher reported daily intake of processed meats and consumption of barbecued/grilled red meat products were associated with increased risk of colorectal cancer in women. IMPACT: Variability in colorectal risk risk by meat type and cooking method should be considered when evaluating meat consumption.

Association of Exposure to Artificial Light at Night While Sleeping With Risk of Obesity in Women.

IMPORTANCE: Short sleep has been associated with obesity, but to date the association between exposure to artificial light at night (ALAN) while sleeping and obesity is unknown. OBJECTIVE: To determine whether ALAN exposure while sleeping is associated with the prevalence and risk of obesity. DESIGN, SETTING, AND PARTICIPANTS: This baseline and prospective analysis included women aged 35 to 74 years enrolled in the Sister Study in all 50 US states and Puerto Rico from July 2003 through March 2009. Follow-up was completed on August 14, 2015. A total of 43 722 women with no history of cancer or cardiovascular disease who were not shift workers, daytime sleepers, or pregnant at baseline were included in the analysis. Data were analyzed from September 1, 2017, through December 31, 2018. EXPOSURES: Artificial light at night while sleeping reported at enrollment, categorized as no light, small nightlight in the room, light outside the room, and light or television in the room. MAIN OUTCOMES AND MEASURES: Prevalent obesity at baseline was based on measured general obesity (body mass index [BMI] ≥30.0) and central obesity (waist circumference [WC] ≥88 cm, waist-to-hip ratio [WHR] ≥0.85, or waist-to-height ratio [WHtR]≥0.5). To evaluate incident overweight and obesity, self-reported BMI at enrollment was compared with self-reported BMI at follow-up (mean [SD] follow-up, 5.7 [1.0] years). Generalized log-linear models with robust error variance were used to estimate multivariable-adjusted prevalence ratios (PRs) and relative risks (RRs) with 95% CIs for prevalent and incident obesity. RESULTS: Among the population of 43 722 women (mean [SD] age, 55.4 [8.9] years), having any ALAN exposure while sleeping was positively associated with a higher prevalence of obesity at baseline, as measured using BMI (PR, 1.03; 95% CI, 1.02-1.03), WC (PR, 1.12; 95% CI, 1.09-1.16), WHR (PR, 1.04; 95% CI, 1.00-1.08), and WHtR (PR, 1.07; 95% CI, 1.04-1.09), after adjusting for confounding factors, with P < .001 for trend for each measure. Having any ALAN exposure while sleeping was also associated with incident obesity (RR, 1.19; 95% CI, 1.06-1.34). Compared with no ALAN, sleeping with a television or a light on in the room was associated with gaining 5 kg or more (RR, 1.17; 95% CI, 1.08-1.27; P < .001 for trend), a BMI increase of 10% or more (RR, 1.13; 95% CI, 1.02-1.26; P = .04 for trend), incident overweight (RR, 1.22; 95% CI,1.06-1.40; P = .03 for trend), and incident obesity (RR, 1.33; 95% CI, 1.13-1.57; P < .001 for trend). Results were supported by sensitivity analyses and additional multivariable analyses including potential mediators such as sleep duration and quality, diet, and physical activity. CONCLUSIONS AND RELEVANCE: These results suggest that exposure to ALAN while sleeping may be a risk factor for weight gain and development of overweight or obesity. Further prospective and interventional studies could help elucidate this association and clarify whether lowering exposure to ALAN while sleeping can promote obesity prevention.

Dietary index scores and invasive breast cancer risk among women with a family history of breast cancer.

BACKGROUND: Many epidemiologic studies have analyzed the relations of individual foods and nutrients and breast cancer risk with inconsistent results. Few studies have examined recommendation-based dietary indices and breast cancer risk. OBJECTIVE: The aim of this study was to determine associations between recommendation-based dietary index scores and incident invasive breast cancer. METHODS: The Sister Study is a prospective cohort of 50,884 US women (baseline: 2003-2009) who had a sister with breast cancer but no prior breast cancer themselves. We created scores for the Dietary Approaches to Stop Hypertension (DASH) diet, Alternative Mediterranean Diet (AMED), and Alternative Healthy Eating Index-2010 (AHEI-2010) from dietary intakes estimated by a baseline-validated Block food-frequency questionnaire (FFQ). We used Cox regression to estimate multivariable-adjusted HRs and 95% CIs for total invasive breast cancer risk and by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status. RESULTS: We documented 1,700 invasive breast cancer cases through 2015 (mean follow-up, 7.6 y). Individuals in the highest quartile of DASH scores had a lower risk of invasive breast cancer compared with those in the lowest quartile (HR: 0.78; 95% CI: 0.67, 0.90; P-trend = 0.001), with stronger associations for ER- (HR: 0.61; 95% CI: 0.40, 0.94; P-trend = 0.006) as well as ER-/PR- and ER-/PR-/HER2- subtypes. AHEI-2010 (HR for highest compared with lowest quartile: 0.90; 95% CI: 0.78, 1.03; P-trend = 0.15) and AMED (HR for highest compared with lowest quartile: 0.90; 95% CI: 0.77, 1.06; P-trend = 0.07) were weakly and nonsignificantly associated with breast cancer risk, but after excluding alcohol, AHEI-2010 was inversely associated with risk of ER-/PR- (HR: 0.64; 95% CI: 0.42, 0.98; P-trend = 0.04) and ER-/PR-/HER2- subtypes. We did not observe any significant interactions by menopausal status or other participant characteristics. CONCLUSIONS: DASH scores were inversely associated with breast cancer risk; DASH and AHEI-2010 scores excluding alcohol were particularly inversely associated with risk of ER-/PR- and ER-/PR-/HER2- breast cancers. This trial was registered at clinicaltrials.gov as NCT00047970.

Dietary inflammatory potential and risk of mortality in metabolically healthy and unhealthy phenotypes among overweight and obese adults.

BACKGROUND & AIMS: This study was designed to investigate the association between the dietary inflammatory index (DII®) scores, metabolic phenotypes, and risk of mortality risk in overweight/obese individuals from a representative sample of the U.S. METHODS: Data from 3733 overweight/obese adults (BMI ≥ 25 kg/m2) aged 20-90 years from the National Health and Nutrition Examination Survey III, 1988-1994 were analyzed; these participants were followed for mortality through December 31, 2011. DII scores were computed based on baseline dietary intake using 24-h dietary recalls. Metabolically unhealthy status was defined as having 2 or more of these metabolic abnormalities: high glucose, insulin resistance, elevated blood pressure, triglycerides, C-reactive protein levels, or low high-density lipoprotein-cholesterol values. RESULTS: In metabolically unhealthy overweight/obese (MUO) individuals, DII score was associated with increased risk of all-cause mortality (HRTertile 3 vs Tertile 1 1.44; 95% CI 1.11-1.86 Ptrend = 0.008; HR1SD increase 1.08; 95% CI 0.99-1.18). Additionally, a stronger association with cardiovascular mortality was observed (HRT3 vs T1 3.29; 95% CI 2.01-5.37 Ptrend < 0.001; HR1SD increase 1.40; 95% CI 1.18-1.66), after adjusting for potential confounders. Furthermore, when analyses were restricted to obese individuals (BMI ≥ 30 kg/m2), the association was more pronounced, especially for cardiovascular mortality (HRT3 vs T1 5.55; 95% CI 2.11-14.57 Ptrend = 0.006; HR1SD increase 1.74; 95% CI 1.21-2.50). No association was observed between DII score and risk of mortality in individuals with metabolically healthy overweight/obese (MHO) phenotype, or for cancer mortality in either MHO or MUO phenotype. CONCLUSIONS: A pro-inflammatory diet appears to increase risk of all-cause and cardiovascular mortality in the MUO phenotype, but not among the MHO phenotype.

Higher diet-dependent acid load is associated with risk of breast cancer: Findings from the sister study.

Dietary factors that contribute to chronic low-grade metabolic acidosis have been linked to breast cancer risk, but to date no epidemiologic study has examined diet-dependent acid load and breast cancer. We used data from 43,570 Sister Study participants who completed a validated food frequency questionnaire at enrollment (2003-2009) and satisfied eligibility criteria. The Potential Renal Acid Load (PRAL) score was used to estimate diet-dependent acid load. Higher scores reflect greater consumption of protein and phosphorus, and lower consumption of potassium, calcium and magnesium. The association between PRAL and breast cancer was evaluated using multivariable Cox proportional hazards regression. We identified 1,614 invasive breast cancers diagnosed at least 1 year after enrollment (mean follow-up, 7.6 years). The highest PRAL quartile, reflecting greater acid-forming potential, was associated with increased risk of breast cancer (HRhighest vs. lowest quartile : 1.21 [95% CI, 1.04-1.41], ptrend = 0.04). The association was more pronounced for estrogen receptor (ER)-negative (HRhighest vs. lowest quartile : 1.67 [95% CI, 1.07-2.61], ptrend = 0.03) and triple-negative breast cancer (HRhighest vs. lowest quartile : 2.20 [95% CI, 1.23-3.95], ptrend = 0.02). Negative PRAL scores, representing consumption of alkaline diets, were associated with decreased risk of ER-negative and triple-negative breast cancer, compared to a PRAL score of 0 representing neutral pH. Higher diet-dependent acid load may be a risk factor for breast cancer while alkaline diets may be protective. Since PRAL scores are positively correlated with meat consumption and negatively correlated with fruit and vegetable intake, results also suggest that diets high in fruits and vegetables and low in meat may be protective against hormone receptor negative breast cancer.