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ObjectiveSeveral attributes of female reproductive history, including age at natural menopause (ANM), have been related to primary open-angle glaucoma (POAG). We assembled 18 previously reported common genetic variants that predict ANM to determine their association with ANM or POAG.MethodsUsing data from the Nurses' Health Study (7,143 women), we validated the ANM weighted genetic risk score in relation to self-reported ANM. Subsequently, to assess the relation with POAG, we used data from 2,160 female POAG cases and 29,110 controls in the National Eye Institute Glaucoma Human Genetics Collaboration Heritable Overall Operational Database (NEIGHBORHOOD), which consists of 8 datasets with imputed genotypes to 5.6+ million markers. Associations with POAG were assessed in each dataset, and site-specific results were meta-analyzed using the inverse weighted variance method.ResultsThe genetic risk score was associated with self-reported ANM (P = 2.2 × 10) and predicted 4.8% of the variance in ANM. The ANM genetic risk score was not associated with POAG (Odds Ratio (OR) = 1.002; 95% Confidence Interval (CI): 0.998, 1.007; P = 0.28). No single genetic variant in the panel achieved nominal association with POAG (P ≥0.20). Compared to the middle 80 percent, there was also no association with the lowest 10 percentile or highest 90 percentile of genetic risk score with POAG (OR = 0.75; 95% CI: 0.47, 1.21; P = 0.23 and OR = 1.10; 95% CI: 0.72, 1.69; P = 0.65, respectively).ConclusionsA genetic risk score predicting 4.8% of ANM variation was not related to POAG; thus, genetic determinants of ANM are unlikely to explain the previously reported association between the two phenotypes.

PurposeAccurate risk assessment is necessary for decision-making around breast cancer prevention. We aimed to develop a breast cancer prediction model for postmenopausal women that would take into account their individualized competing risk of non-breast cancer death.MethodsWe included 73,066 women who completed the 2004 Nurses' Health Study (NHS) questionnaire (all ≥57 years) and followed participants until May 2014. We considered 17 breast cancer risk factors (health behaviors, demographics, family history, reproductive factors) and 7 risk factors for non-breast cancer death (comorbidities, functional dependency) and mammography use. We used competing risk regression to identify factors independently associated with breast cancer. We validated the final model by examining calibration (expected-to-observed ratio of breast cancer incidence, E/O) and discrimination (c-statistic) using 74,887 subjects from the Women's Health Initiative Extension Study (WHI-ES; all were ≥55 years and followed for 5 years).ResultsWithin 5 years, 1.8 % of NHS participants were diagnosed with breast cancer (vs. 2.0 % in WHI-ES, p = 0.02), and 6.6 % experienced non-breast cancer death (vs. 5.2 % in WHI-ES, p

Background: We investigated the associations of reproductive factors known to influence breast cancer risk with the expression of breast stem cell markers CD44, CD24, and ALDH1A1 in benign breast biopsy samples. Methods: We included 439 cancer-free women with biopsy-confirmed benign breast disease within the Nurses' Health Study (NHS) and NHSII. The data on reproductive and other breast cancer risk factors were obtained from biennial questionnaires. Immunohistochemistry (IHC) was performed on tissue microarrays. For each core, the IHC expression was assessed using a semi-automated platform and expressed as % of cells that stained positive for a specific marker out of the total cell count. Generalized linear regression was used to examine the associations of reproductive factors with a log-transformed expression of each marker (in epithelium and stroma), adjusted for other breast cancer risk factors. Results: In multivariate analysis, the time between menarche and age at first birth was inversely associated with CD44 in epithelium (β per 5 years = -0.38, 95% CI -0.69; -0.06). Age at first birth and the time between menarche and age at first birth were inversely associated with ALDH1A1 (stroma: β per 5 years = -0.43, 95% CI -0.76; -0.10 and β = -0.47, 95% CI -0.79; -0.15, respectively; epithelium: β = -0.15, 95% CI -0.30; -0.01 and β = -0.17, 95% CI -0.30; -0.03, respectively). Time since last pregnancy was inversely associated with stromal ALDH1A1 (β per 5 years = -0.55, 95% CI -0.98; -0.11). No associations were found for CD24. The observed associations were similar in premenopausal women. In postmenopausal women, lifetime duration of breastfeeding was inversely associated with stromal ALDH1A1 expression (β for ≥24 vs. 0 to <1 months = -2.24, 95% CI 3.96; -0.51, p-trend = 0.01). Conclusion: Early-life reproductive factors may influence CD44 and ALDH1A1 expression in benign breast tissue. [ABSTRACT FROM AUTHOR]

IntroductionWe examined the association between endogenous sex hormones and both objective and subjective measures of cognitive function.MethodsWe followed 3044 women up to 23 years in a prospective cohort study. We measured plasma levels of estrone, estrone sulfate, estradiol, androstenedione, testosterone, dehydroepiandrosterone (DHEA), and dehydroepiandrosterone sulfate (DHEA-S) in 1989-1990, conducted neuropsychologic testing in 1999-2008, and inquired about subjective cognition in 2012.ResultsOverall, we observed little relation between plasma levels of hormones and either neuropsychologic test performance or subjective cognition. However, after adjustment for age and education, we observed a borderline significant association of higher levels of plasma estrone with higher scores for both overall cognition (P trend = .10) and verbal memory (P trend = .08).DiscussionThere were no clear associations of endogenous hormone levels at midlife and cognition in later life, although a suggested finding of higher levels of plasma estrone associated with better cognitive function merits further research.

The relationship between various diet quality indices and risk of type 2 diabetes (T2D) remains unsettled. We compared associations of 4 diet quality indices--the Alternate Mediterranean Diet Index, Healthy Eating Index 2010, Alternate Healthy Eating Index 2010, and the Dietary Approaches to Stop Hypertension (DASH) Index--with reported T2D in the Women's Health Initiative, overall, by race/ethnicity, and with/without adjustment for overweight/obesity at enrollment (a potential mediator). This cohort (n = 101,504) included postmenopausal women without T2D who completed a baseline food frequency questionnaire from which the 4 diet quality index scores were derived. Higher scores on the indices indicated a better diet. Cox regression was used to estimate multivariate hazard ratios for T2D. Pearson coefficients for correlation among the indices ranged from 0.55 to 0.74. Follow-up took place from 1993 to 2013. During a median 15 years of follow-up, 10,815 incident cases of T2D occurred. For each diet quality index, a 1-standard-deviation higher score was associated with 10%-14% lower T2D risk (P < 0.001). Adjusting for overweight/obesity at enrollment attenuated but did not eliminate associations to 5%-10% lower risk per 1-standard-deviation higher score (P < 0.001). For all 4 dietary indices examined, higher scores were inversely associated with T2D overall and across racial/ethnic groups. Multiple forms of a healthful diet were inversely associated with T2D in these postmenopausal women.

BackgroundThere is limited evidence that supports etiologically distinct molecular subtypes of prostate cancer, the identification of which may improve prevention. Given their antioxidant properties, we hypothesized that lycopene and tomato sauce may be especially protective against diseases harboring the common gene fusion transmembrane protease, serine 2 (TMPRSS2):v-ets avian erythroblastosis virus E26 oncogene homolog (ERG).ObjectiveWe aimed to examine associations between estimated lycopene and tomato sauce intake and the risk of prostate cancer defined by ERG protein expression subtype.DesignOur study population consisted of a prospective cohort of 46,719 men from the Health Professionals Follow-Up Study. TMPRSS2:ERG was assessed by ERG immunohistochemistry on tumor tissue microarrays constructed from radical prostatectomy specimens. We used multivariable competing risk models to calculate HRs and 95% CIs for the risk of ERG-positive and, separately, ERG-negative disease. We implemented inverse probability weighting to account for evaluating ERG status only in surgically treated cases.ResultsDuring 23 y of follow-up, 5543 men were diagnosed with prostate cancer, among whom 884 were assayed for ERG (426 ERG-positive). With inclusion of only the latter cases, increasing cumulative average tomato sauce intake was associated with a decreased risk of prostate cancer overall (≥2 servings/wk compared with

BackgroundThe Breast Cancer Risk Assessment Tool (BCRAT, "Gail model") is commonly used for breast cancer prediction; however, it has not been validated for women age 75 years and older.MethodsWe used Nurses' Health Study (NHS) data beginning in 2004 and Women's Health Initiative (WHI) data beginning in 2005 to compare BCRAT's performance among women age 75 years and older with that in women age 55 to 74 years in predicting five-year breast cancer incidence. BCRAT risk factors include: age, race/ethnicity, age at menarche, age at first birth, family history, history of benign breast biopsy, and atypia. We examined BCRAT's calibration by age by comparing expected/observed (E/O) ratios of breast cancer incidence. We examined discrimination by computing c-statistics for the model by age. All statistical tests were two-sided.ResultsSeventy-three thousand seventy-two NHS and 97 081 WHI women participated. NHS participants were more likely to be non-Hispanic white (96.2% vs 84.7% in WHI, P < .001) and were less likely to develop breast cancer (1.8% vs 2.0%, P = .02). E/O ratios by age in NHS were 1.16 (95% confidence interval [CI] = 1.09 to 1.23, age 57-74 years) and 1.31 (95% CI = 1.18 to 1.45, age ≥ 75 years, P = .02), and in WHI 1.03 (95% CI = 0.97 to 1.09, age 55-74 years) and 1.10 (95% CI = 1.00 to 1.21, age ≥ 75 years, P = .21). E/O ratio 95% confidence intervals crossed one among women age 75 years and older when samples were limited to women who underwent mammography and were without significant illness. C-statistics ranged between 0.56 and 0.58 in both cohorts regardless of age.ConclusionsBCRAT accurately predicted breast cancer for women age 75 years and older who underwent mammography and were without significant illness but had modest discrimination. Models that consider individual competing risks of non-breast cancer death may improve breast cancer risk prediction for older women.

Obesity is well established as a cause of postmenopausal breast cancer incidence and mortality. In contrast, adiposity in early life reduces breast cancer incidence. However, whether short-term weight change influences breast cancer risk is not well known. We followed a cohort of 77,232 women from 1980 to 2006 (1,445,578 person-years), with routinely updated risk factor information, documenting 4196 incident cases of invasive breast cancer. ER and PR status were obtained from pathology reports and medical records yielding a total of 2033 ER+/PR+ tumors, 595 ER-/PR- tumors, 512 ER+/PR- tumors. The log incidence breast cancer model was used to assess the association of short-term weight gain (over past 4 years) while controlling for average BMI before and after menopause. Short-term weight change was significantly associated with breast cancer risk (RR 1.20; 95 % CI 1.09-1.33) for a 4-year weight gain of ≥15 lbs versus no change (≤5 lbs) (P_trend < 0.001). The association was stronger for premenopausal women (RR 1.38; 95 % CI 1.13-1.69) (P_trend = 0.004) than for postmenopausal women (RR 1.10; 95 % CI 0.97-1.25) (P_trend = 0.063). Short-term weight gain during premenopause had a stronger association for ER+/PR- (RR per 25 lb weight gain = 2.19; 95 % CI 1.33-3.61, P = 0.002) and ER-/PR- breast cancer (RR per 25 lb weight gain = 1.61; 95 % CI 1.09-2.38, P = 0.016) than for ER+/PR+ breast cancer (RR per 25 lb weight gain = 1.13; 95 % CI 0.89-1.43, P = 0.32). There are deleterious effects of short-term weight gain, particularly during pre-menopause, even after controlling for average BMI before and after menopause. The association was stronger for ER+/PR- and ER-/PR- than for ER+/PR+ breast cancer.

BackgroundYouth spend more time with screens than any activity except sleeping. Screen time is a risk factor for obesity, possibly because of the influence of food and beverage advertising on diet.ObjectiveWe sought to assess longitudinal relations of screen time [ie, television, electronic games, digital versatile discs (DVDs)/videos, and total screen time] with the 2-y changes in consumption of foods of low nutritional quality (FLNQ) that are commonly advertised on screens [ie, sugar-sweetened beverages, fast food, sweets, salty snacks, and the sum of these foods (total FLNQ)] and fruit and vegetables.DesignWith the use of 2004, 2006, and 2008 waves of the Growing Up Today Study II, which consisted of a cohort of 6002 female and 4917 male adolescents aged 9-16 y in 2004, we assessed screen time (change and baseline) in relation to the 2-y dietary changes. Regression models included 4604 girls and 3668 boys with complete screen time and diet data on ≥2 consecutive questionnaires.ResultsEach hour-per-day increase in television, electronic games, and DVDs/videos was associated with increased intake of total FLNQ (range: 0.10-0.28 servings/d; P < 0.05). Each hour-per-day increase in total screen time predicted increased intakes of sugar-sweetened beverages, fast food, sweets, and salty snacks (range: 0.02-0.06 servings/d; P < 0.001) and decreased intakes of fruit and vegetables (range: -0.05 to -0.02 servings/d; P < 0.05). Greater screen time at baseline (except electronic games in boys) was associated with subsequent increased intake of total FLNQ, and greater screen time at baseline (except DVDs/videos) was associated with decreased intake of fruit and vegetables (P < 0.05). Across sex and food groups and in sensitivity analyses, television was most consistently associated with dietary changes.ConclusionsIncreases in screen time were associated with increased consumption of foods and beverages of low nutritional quality and decreased consumption of fruit and vegetables. Our results caution against excessive use of screen media, especially television, in youth.

ObjectiveSales of regular soda were declining, but sales of other sweetened beverages, such as sports drinks, were increasing. Our objective was to determine the prospective associations between sports drinks and body mass index (BMI) gains among adolescents and young adults.Methods4121 females and 3438 males in the Growing Up Today Study II, aged 9-16 in 2004, from across the United States were followed prospectively. Data were collected by questionnaire in 2004, 2006, 2008, and 2011. Servings per day of various beverages were assessed with a food frequency questionnaire.ResultsAmong the girls, each serving per day of sports drink predicted an increase of 0.3 BMI units (95% confidence interval (CI) CI 0.03-0.54) more than their peers over the next 2-3 years. Among the males, each serving of sports drinks predicted a 0.33 BMI (95% CI 0.09, 0.66) increase. In addition, boys who increased their intake over the 2-3 year interval gained significantly more than their peers during the same time interval.ConclusionsIntake of sports drinks predicted larger increases in BMI among both females and males. Our results suggest that school policies focused on obesity prevention should be augmented to restrict sports drinks.

Context Black women have a higher prevalence of hypertension as compared to White women. Differences in dietary sodium intake have been implicated as a contributing factor for the disparities in hypertension. Objective Our objective was to understand whether young Black women would have higher systolic blood pressure (SBP) than White women even on controlled sodium diets and to determine whether SBP differences were due to differences in dietary sodium intake and/or aldosterone regulation. Design The analyses included 525 hypertensive and normotensive women (ages 18-71) from the International Hypertensive Pathotype consortium, who were maintained on liberal sodium (LIB; >200 mEq sodium/day) and restricted sodium (RES; 10 mEq sodium/day) diets. Results Multivariate regression analyses (adjusted for age, race, study site, body mass index) found that Black women (ages 18-50) had significantly higher SBP than White women on both sodium diets: +8.7 ± 2.7 mmHg (P -value =.002) on a LIB diet and +8.5 ± 2.5 mmHg (P -value =.001) on a RES diet. Even among 18- to 35-year-olds—who were normotensive and nonobese—Black women had higher SBP: +7.9 ± 2.4 mmHg (P -value =.001) on a LIB diet and +7.6 ± 2.7 mmHg (P -value =.005) on a RES diet. Younger Black women also had higher plasma aldosterone concentration to plasma renin activity ratio (ARR) on both LIB and RES diets as well as a higher sodium-modulated aldosterone suppression-stimulation index—an indicator of aldosterone dysregulation. In younger Black women—but not in White women—there was a significant association between SBP and ARR on both LIB and RES diets. Conclusion Young Black women had increased SBP and ARR as compared to White women on LIB and RES diets, which offers insights into the possible mechanisms for the increased hypertension and cardiovascular disease risk in an at-risk and understudied population. [ABSTRACT FROM AUTHOR]

Background To support mammography screening decision making, we developed a competing-risk model to estimate 5-year breast cancer risk and 10-year nonbreast cancer death for women aged 55 years and older using Nurses' Health Study data and examined model performance in the Black Women's Health Study (BWHS). Here, we examine model performance in predicting 10-year outcomes in the BWHS, Women's Health Initiative-Extension Study (WHI-ES), and Multiethnic Cohort (MEC) and compare model performance to existing breast cancer prediction models. Methods We used competing-risk regression and Royston and Altman methods for validating survival models to calculate our model's calibration and discrimination (C index) in BWHS (n = 17 380), WHI-ES (n = 106 894), and MEC (n = 49 668). The Nurses' Health Study development cohort (n = 48 102) regression coefficients were applied to the validation cohorts. We compared our model's performance with breast cancer risk assessment tool (Gail) and International Breast Cancer Intervention Study (IBIS) models by computing breast cancer risk estimates and C statistics. Results When predicting 10-year breast cancer risk, our model's C index was 0.569 in BWHS, 0.572 in WHI-ES, and 0.576 in MEC. The Gail model's C statistic was 0.554 in BWHS, 0.564 in WHI-ES, and 0.551 in MEC; IBIS's C statistic was 0.547 in BWHS, 0.552 in WHI-ES, and 0.562 in MEC. The Gail model underpredicted breast cancer risk in WHI-ES; IBIS underpredicted breast cancer risk in WHI-ES and in MEC but overpredicted breast cancer risk in BWHS. Our model calibrated well. Our model's C index for predicting 10-year nonbreast cancer death was 0.760 in WHI-ES and 0.763 in MEC. Conclusions Our competing-risk model performs as well as existing breast cancer prediction models in diverse cohorts and predicts nonbreast cancer death. We are developing a website to disseminate our model. [ABSTRACT FROM AUTHOR]

We evaluated the validity and reproducibility of a semiquantitative food frequency questionnaire (FFQ) for measuring intakes of 149 foods and 25 food groups among 736 participants of the Women's Lifestyle Validation Study (WLVS, 2010–2012) and 649 participants of the Men's Lifestyle Validation Study (MLVS, 2011–2013). Validity of the FFQ compared with two 7-day dietary records measured 6 months apart and the reproducibility between 2 FFQs administered 1 year apart (FFQ1 and FFQ2) were assessed using Spearman correlations and intraclass correlation coefficients. The average 1-year reproducibility of FFQ-measured foods was 0.64 in both the WLVS and MLVS. Reproducibility of the food groups (mean = 0.71 among women and 0.72 among men) was generally higher than that for individual foods. Among women, the average validity correlation for individual foods was 0.59 when comparing FFQ2 with the 7-day dietary records. Among men, the corresponding average validity correlation was 0.61. Compared with individual foods, food groups had slightly higher validity correlations in both women (range, 0.45–0.92; mean = 0.61) and men (range, 0.46–0.88; mean = 0.65). This study reaffirms that the FFQ performs well in measuring most foods and food groups and provides data to adjust for measurement errors in epidemiologic studies of foods and food groups. [ABSTRACT FROM AUTHOR]