Supplementary Table S1: Cohorts participating in analysis of coffee variables, Liver Cancer Pooling Project. Supplementary Table S2: Assessment of coffee consumption, Liver Cancer Pooling Project. Supplementary Table S3: Characteristics of participants in the Liver Cancer Pooling Project by coffee drinking. Supplementary Table S4: Adjusted Hazard Ratios (HR) and 95% Confidence Intervals (CI) for Associations Between Coffee Consumption and Intrahepatic Cholangiocarcinoma Incidence by Sex, Smoking Status, Body Mass Index, and Diabetes, Liver Cancer Pooling Project. Supplementary Table S5: Adjusted Hazard Ratios (HR) and 95% Confidence Intervals (CI) for Associations Between Coffee Consumption and Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma Incidence by Caffeine Content; Sensitivity Analysis Excluding WHI and Jointly Modeling Caffeine Content and Drinking Intensity, Liver Cancer Pooling Project. Supplementary Table S6: Adjusted Hazard Ratios (HR) and 95% Confidence Intervals (CI) for Associations Between Coffee Consumption and Suspected Hepatocellular Carcinoma Incidence by Caffeine Content, Liver Cancer Pooling Project. Supplementary Table S7: Adjusted Hazard Ratios (HR) and 95% Confidence Intervals (CI) for Associations Between Coffee Consumption and Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma Incidence by Caffeine Content in the AARP Study, Liver Cancer Pooling Project. Supplementary Table S8: Adjusted Hazard Ratios (HR) and 95% Confidence Intervals (CI) for Associations Between Coffee Consumption and Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma Incidence by Sex in the AARP Study, Liver Cancer Pooling Project. Supplementary Table S9: Adjusted Hazard Ratios (HR) and 95% Confidence Intervals (CI) for Associations Between Coffee Consumption and Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma Incidence by Caffeine Content excluding the AARP Study, Liver Cancer Pooling Project. Supplementary Table S10: Adjusted Hazard Ratios (HR) and 95% Confidence Intervals (CI) for Associations Between Coffee Consumption and Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma Incidence by Sex excluding the AARP Study, Liver Cancer Pooling Project. Supplementary Figure S1: Meta-influence Graph of the Influence of Individuals Studies for Associations between Coffee Consumption versus No Consumption and Hepatocellular Carcinoma, Liver Cancer Pooling Project.

Breast cancer mortality is higher in Black women than in White women. The prevalence of type 2 diabetes mellitus is also higher, yet data on whether diabetes affects breast cancer mortality in this population are lacking. We investigated the relation of diabetes at the time of breast cancer diagnosis to breast cancer mortality in the Black Women’s Health Study, a prospective cohort study.

Purpose Breast cancer risk prediction models have underestimated risk for African American women, contributing to lower recruitment rates in prevention trials. A model previously developed for African American women was found to underestimate risk in the Black Women's Health Study (BWHS). Methods We developed a breast cancer risk model for African American women using relative risks derived from 10 years of follow-up of BWHS participants age 30 to 69 years at baseline. Using the subsequent 5 years of follow-up data, we evaluated calibration as the ratio of expected to observed number of breast cancers and assessed discriminatory accuracy using the concordance statistic. Results The BWHS model included family history, previous biopsy, body mass index at age 18 years, age at menarche, age at first birth, oral contraceptive use, bilateral oophorectomy, estrogen plus progestin use, and height. There was good agreement between predicted and observed number of breast cancers overall (expected-to-observed ratio, 0.96; 95% CI, 0.88 to 1.05) and in most risk factor categories. Discriminatory accuracy was higher for women younger than age 50 years (area under the curve [AUC], 0.62; 95% CI, 0.58 to 0.65) than for women age ≥ 50 years (AUC, 0.56; 95% CI, 0.53 to 0.59). Using a 5-year predicted risk of 1.66% or greater as a cut point, 2.8% of women younger than 50 years old and 32.2% of women ≥ 50 years old were classified as being at elevated risk of invasive breast cancer. Conclusion The BWHS model was well calibrated overall, and the predictive ability was best for younger women. The proportion of women predicted to meet the 1.66% cut point commonly used to determine eligibility for breast cancer prevention trials was greatly increased relative to previous models.

Abstract Background: Coffee consumption has been reported to be inversely associated with hepatocellular carcinoma (HCC), the most common type of liver cancer. Caffeine has chemopreventive properties, but whether caffeine is responsible for the coffee–HCC association is not well studied. In addition, few studies have examined the relationship by sex, and no studies have examined whether there is an association between coffee and intrahepatic cholangiocarcinoma (ICC), the second most common type of liver cancer. Methods: In the Liver Cancer Pooling Project, a consortium of U.S.-based cohort studies, data from 1,212,893 individuals (HCC, n = 860; ICC, n = 260) in nine cohorts were pooled. Multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI) were estimated using proportional hazards regression. Results: Higher coffee consumption was associated with lower risk of HCC (HR>3 cups/day vs. non-drinker, 0.73; 95% CI, 0.53–0.99; Ptrend cups/day = <0.0001). More notable reduced risk was seen among women than men (Pinteraction = 0.07). Women who consumed more than three cups of coffee per day were at a 54% lower risk of HCC (HR, 0.46; 95% CI, 0.26–0.81), whereas men had more modest reduced risk of HCC (HR, 0.93; 95% CI, 0.63–1.37). The associations were stronger for caffeinated coffee (HR>3 cups/day vs. non-drinker, 0.71; 95% CI, 0.50–1.01) than decaffeinated coffee (HR, 0.92; 95% CI, 0.55–1.54). There was no association between coffee consumption and ICC. Conclusions: These findings suggest that, in a U.S. population, coffee consumption is associated with reduced risk of HCC. Impact: Further research into specific coffee compounds and mechanisms that may account for these associations is needed. Cancer Epidemiol Biomarkers Prev; 24(9); 1398–406. ©2015 AACR.

African American women are more likely to undergo hysterectomy, with or without bilateral oophorectomy, at younger ages than white women. It is well established that women who have a bilateral oophorectomy at younger ages are at reduced risk of breast cancer, and there is some evidence of an increased risk of colorectal and lung cancer.

BACKGROUND:Diet quality has been inversely associated with overall mortality in white populations, but the evidence in African-American populations is limited. OBJECTIVE:The goal of the present study was to assess diet quality in relation to all-cause mortality in the Black Women's Health Study, a follow-up study of African-American women begun in 1995. METHODS:Data used in this study were obtained via biennial questionnaires from 1995 to 2011. Based on food-frequency questionnaire data collected in 1995 and 2001, we calculated an index-based diet quality score [Dietary Approaches to Stop Hypertension (DASH)] and derived dietary patterns (prudent and Western) with the use of factor analysis. We followed 37,001 women who were aged 30-69 y and free of cancer, cardiovascular disease, and diabetes at baseline for mortality through 2011. Multivariable Cox regression was used to estimate HRs and 95% CIs. Analyses were conducted in 2014. RESULTS:Based on a total of 1678 deaths during 16 y of follow-up, higher DASH scores were associated with reduced all-cause mortality (HR: 0.75; 95% CI: 0.63, 0.89 for highest vs. lowest quintiles). The DASH components most strongly associated with lower mortality were high intake of whole grains and low intake of red and processed meat. A Western dietary pattern, characterized by high intake of red and processed meat, was associated with increased all-cause mortality rates (HR: 1.37; 95% CI: 1.17, 1.60 for highest vs. lowest quintiles of score); a prudent dietary pattern was not associated with risk. CONCLUSION:A DASH-style diet high in intake of whole grains and low in consumption of red meat is associated with reduced mortality rates in healthy African-American women.

Background: Gestational diabetes is a precursor to type 2 diabetes. Little is known about the relation of other common pregnancy complications, such as preterm birth, to risk of type 2 diabetes. Methods: We assessed preterm birth in relation to incident type 2 diabetes among 31,101 participants from the Black Women's Health Study. Preterm birth, defined as <37 weeks gestation, was reported at baseline (1995) and on subsequent biennial follow-up questionnaires. Self-reported type 2 diabetes diagnoses were ascertained on biennial questionnaires through 2009. We used Cox proportional hazards models to calculate incidence rate ratios (IRRs) and 95% confidence intervals (CIs), adjusting for potential confounders. Results: At baseline, 5162 participants (19%) reported a history of giving birth preterm, of which 16% occurred at <32 weeks gestation. A total of 3261 cases of type 2 diabetes were ascertained during follow-up. Ever having had a preterm birth was associated with a 20% increased risk (95% CI = 1.11–1.31) after adjusting for age at first birth, family history of diabetes, education, respondent having been born preterm, and body mass index. Gestational age <32 weeks was associated with the greatest risk (IRR = 1.27 [95% CI = 1.06–1.51]). Among women without a history of gestational diabetes, the IRR for type 2 diabetes among women who ever had a preterm birth was 1.17 (1.07–1.28). Conclusion: Preterm birth was associated with an increased type 2 diabetes risk in black mothers, independent of gestational diabetes.

Pooled analyses among whites and East Asians have demonstrated positive associations between all-cause mortality and body mass index (BMI), but studies of African Americans have yielded less consistent results. We examined the association between BMI and all-cause mortality in a sample of African Americans pooled from seven prospective cohort studies: NIH-AARP, 1995-2009; Adventist Health Study 2, 2002-2008; Black Women's Health Study, 1995-2009; Cancer Prevention Study II, 1982-2008; Multiethnic Cohort Study, 1993-2007; Prostate, Lung, Colorectal and Ovarian Screening Trial, 1993-2009; Southern Community Cohort Study, 2002-2009. 239,526 African Americans (including 100,175 never smokers without baseline heart disease, stroke, or cancer), age 30-104 (mean 52) and 71% female, were followed up to 26.5 years (mean 11.7). Hazard ratios (HR) and 95% confidence intervals (CI) for mortality were derived from multivariate Cox proportional hazards models. Among healthy, never smokers (11,386 deaths), HRs (CI) for BMI 25-27.4, 27.5-29.9, 30-34.9, 35-39.9, 40-49.9, and 50-60 kg/m(2) were 1.02 (0.92-1.12), 1.06 (0.95-1.18), 1.32 (1.18-1.47), 1.54 (1.29-1.83), 1.93 (1.46-2.56), and 1.93 (0.80-4.69), respectively among men and 1.06 (0.99-1.15), 1.15 (1.06-1.25), 1.24 (1.15-1.34), 1.58 (1.43-1.74), 1.80 (1.60-2.02), and 2.31 (1.74-3.07) respectively among women (reference category 22.5-24.9). HRs were highest among those with the highest educational attainment, longest follow-up, and for cardiovascular disease mortality. Obesity was associated with a higher risk of mortality in African Americans, similar to that observed in pooled analyses of whites and East Asians. This study provides compelling evidence to support public health efforts to prevent excess weight gain and obesity in African Americans.

Purpose Prenatal DES exposure has been associated with increased risk of breast cancer, but the mechanisms are unknown. Larger bra cup size has also been associated with increased breast cancer risk, although not consistently. We investigated the relation of prenatal DES exposure to mammary gland mass, as estimated by bra cup size. Methods In 2006, 3,222 DES-exposed and 1,463 unexposed women reported their bra cup size, band size (chest circumference), and weight at age 20. Prevalence ratios (PR) were calculated for DES exposure in relation to large bra cup size, with control for year of birth and study cohort. Primary analyses were carried out among women who reported a chest circumference of no more than 32 inches because their cup size would be less influenced by fat mass. Results Within this group, DES-exposed women had an estimated 45 % increased prevalence (95 % CI 0.97‐2.18) of large cup size (C or greater) relative to unexposed women. The PR was further increased among women in this group who had a body mass index of 21 at age 20: PR = 1.83 (95 % CI 1.11‐3.00). The PR for high-dose DES exposure relative to no exposure was 1.67, 95 % CI 1.02‐2.73, whereas there was no association of bra cup size with low-dose exposure. Conclusions These results provide support for the hypothesis that in utero DES exposure may result in greater mammary gland mass. Taken together with previous research on bra size and breast cancer risk, these findings suggest a mechanism for a possible association of in utero DES exposure with increased risk of breast cancer.

OBJECTIVES:Early age at natural menopause has been associated with increased all-cause mortality in several studies, although the literature is not consistent. This relation has not been examined among African American women.STUDY DESIGN:Data were from the Black Women's Health Study, a follow-up study of African-American women enrolled in 1995. Among 11,212 women who were naturally menopausal at entry to the study or during follow-up through 2008, we assessed the relation of age at natural menopause to all-cause and cause-specific mortality. At baseline and biennially, participants reported on reproductive and medical history, including gynecologic surgeries and exogenous hormone use. Mortality data were obtained from the National Death Index. Multivariable Cox proportional hazard models were used to estimate mortality rate ratios (MRR) and 95% confidence intervals (CI) for categories of age at menopause.RESULTS:Of 692 deaths identified during 91,829 person years of follow-up, 261 were due to cancer, 199 to cardiovascular diseases and 232 to other causes. Natural menopause before age 40 was associated with increased all-cause mortality (MRR=1.34, 95% CI 0.96-1.84, relative to menopause at 50-54 years; P-trend=0.04) and with the subcategories of death considered - cancer, cardiovascular disease, and all other causes. The associations were present among never and ever users of postmenopausal female hormones and among never and ever smokers.CONCLUSIONS:In this large prospective cohort of African-American women, natural menopause before age 40 was associated with a higher rate of all-cause and cause-specific mortality. These findings provide support for the theory that natural menopause before age 40 may be a marker of accelerated somatic aging.

The prevalence of obesity [body mass index (BMI) ≥30 kg/m2] is high among African American women, with most weight gain occurring before middle age. We assessed diet quality, as measured by the Alternate Healthy Eating Index-2010 (AHEI-2010) and the Dietary Approaches to Stop Hypertension (DASH) diet score in relation to incident obesity in the Black Women's Health Study. Prospective data were collected via biennial questionnaires from 1995 to 2011. AHEI-2010 and DASH scores were calculated from food-frequency questionnaire data collected in 1995 and 2001. We restricted the analysis to 19,885 nonobese women aged 21-39 y at baseline. Multivariable Cox regression was used to estimate HRs and 95% CIs. Among women with consistent diet scores in 1995 and 2001, higher diet quality scores were inversely associated with obesity incidence: the multivariable HRs comparing highest with lowest quintiles of the AHEI-2010 and DASH scores were 0.76 (95% CI: 0.58, 0.98) and 0.68 (95% CI: 0.53, 0.88), respectively, among women with a BMI in the normal range (18.5-24.9 kg/m2) at baseline. There were no significant associations among women who were overweight at baseline. The findings suggest that a high-quality diet that is sustained over time is associated with reduced obesity risk among young African American women with a normal BMI at baseline.

Active smoking and passive smoking have been associated with increased risk of breast cancer. The purpose of the present study was to prospectively assess associations of smoking with breast cancer and identify subgroups at higher risk among African-American women.

Purpose The incidence of estrogen receptor positive (ER+) breast cancer is higher among white women relative to black women. In two large prospective cohorts, the Black Women’s Health Study (BWHS) and the Nurses’ Health Study II (NHSII), we investigated whether reproductive factors explain the difference. Methods During 1,582,083 person-years of follow-up of 140,914 women observed from 1995 to 2007, 327 ER+ breast cancers were identified among black women in BWHS and NHSII and 1,179 among white women in NHSII. Cox proportional hazards regression models, stratified by race and pooled, were used to estimate hazard ratios (HR) and 95 % confidence intervals (CI) for the association of race, parity, age at first birth, and lactation in relation to risk of ER+ cancer with adjustment for age and other breast cancer risk factors. Results Age at first birth differed markedly in the two groups, with 66 % of parous black women having their first child before age 25 as compared with 36 % of white women. Each additional year of age at first birth was associated with a 4 % increased risk of ER+ breast cancer among both racial groups. Relative to nulliparous women, parous women were at decreased risk of ER+ breast cancer (HR 0.59, 95 % CI 0.20, 1.77), in black women and (HR 0.63, 95 % CI 0.45, 0.87) in white women. The HR for the association of black race with ER+ cancer was 0.67 (95 % CI 0.53, 0.84) in a model that adjusted for age only, 0.77 (95 % CI 0.61, 0.99) in a model that controlled for parity, age at first birth, and other reproductive/hormonal factors, and 0.83 (95 % CI 0.70, 0.98) in a model that additionally controlled for other breast cancer risk factors such as alcohol consumption and use of hormone supplements. Similar associations were seen among premenopausal women and in an analysis restricted to ER+PR+ tumors. Conclusions Reproductive factors explained some of the higher incidence of ER+ tumors among white women as compared to black women.

Prenatal DES exposure has been associated with increased risk of breast cancer, but the mechanisms are unknown. Larger bra cup size has also been associated with increased breast cancer risk, although not consistently. We investigated the relation of prenatal DES exposure to mammary gland mass, as estimated by bra cup size.

BACKGROUND The prevalence of obesity is disproportionately high in African American women, and consumption of fast foods and sugar-sweetened soft drinks is also especially high among African Americans. OBJECTIVE We investigated the relation of intakes of sugar-sweetened soft drinks and specific types of restaurant foods to obesity in the Black Women's Health Study. DESIGN In this prospective cohort study, 19,479 non-obese women aged 21-39 years at baseline were followed for 14 years (1995-2009). Dietary intake was assessed by validated food frequency questionnaire in 1995 and 2001. MAIN OUTCOME MEASURES Cox regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association of intakes of restaurant foods and sugar-sweetened soft drinks with incident obesity. RESULTS Higher intakes of burgers from restaurants and sugar-sweetened soft drinks were associated with greater risk of becoming obese. The associations were present in models that included both factors and adjusted for overall dietary pattern. The HR of obesity in relation to restaurant burger consumption of > or = 2 times/week compared with < 5 times/year was 1.26 (95% CI: 1.14-1.40; P-trend<.001). For sugar-sweetened soft drink intake, the HR was 1.10 (95% CI: .99-1.23; P-trend = .14) for > or = 2 drinks/day compared with < 1 drink/month. The associations were stronger among women younger than age 30 with normal weight at baseline. CONCLUSIONS Frequent consumption of burgers from restaurants and sugar-sweetened soft drinks contribute to obesity among young African American women.

BACKGROUND Estrogen receptor-negative (ER(-)) breast cancer has few known or modifiable risk factors. Because ER(-) tumors account for only 15% to 20% of breast cancers, large pooled analyses are necessary to evaluate precisely the suspected inverse association between fruit and vegetable intake and risk of ER(-) breast cancer. METHODS Among 993 466 women followed for 11 to 20 years in 20 cohort studies, we documented 19 869 estrogen receptor positive (ER(+)) and 4821 ER(-) breast cancers. We calculated study-specific multivariable relative risks (RRs) and 95% confidence intervals (CIs) using Cox proportional hazards regression analyses and then combined them using a random-effects model. All statistical tests were two-sided. RESULTS Total fruit and vegetable intake was statistically significantly inversely associated with risk of ER(-) breast cancer but not with risk of breast cancer overall or of ER(+) tumors. The inverse association for ER(-) tumors was observed primarily for vegetable consumption. The pooled relative risks comparing the highest vs lowest quintile of total vegetable consumption were 0.82 (95% CI = 0.74 to 0.90) for ER(-) breast cancer and 1.04 (95% CI = 0.97 to 1.11) for ER(+) breast cancer (P (common-effects) by ER status < .001). Total fruit consumption was non-statistically significantly associated with risk of ER(-) breast cancer (pooled multivariable RR comparing the highest vs lowest quintile = 0.94, 95% CI = 0.85 to 1.04). CONCLUSIONS We observed no association between total fruit and vegetable intake and risk of overall breast cancer. However, vegetable consumption was inversely associated with risk of ER(-) breast cancer in our large pooled analyses.

BACKGROUND:Obesity occurs more commonly among African-American women than among other racial/ethnic groups, and most weight gain occurs before middle age.PURPOSE:The study prospectively investigated the relationship of vigorous exercise and brisk walking to the incidence of obesity (BMI ≥ 30) among African-American women aged <40 years.METHODS:During 1995-2009 in the Black Women's Health Study, the current authors followed 20,259 African-American women who were aged <40 years and not obese at baseline. BMI, exercise, and walking were assessed at baseline and on biennial follow-up questionnaires. Data for BMI were collected through 2009. Data for exercise and walking were collected through 2007. Validation and reproducibility data indicated that reporting was more accurate for vigorous exercise than for brisk walking. Cox proportional hazards models estimated incidence rate ratios (IRRs) and 95% CIs of incident obesity for hours/week of vigorous exercise and walking relative to "little or no exercise" (<1 hour/week of vigorous exercise and <1 hour/week of brisk walking). The analyses were conducted in 2012.RESULTS:The incidence of obesity decreased with increasing vigorous exercise; the IRR was 0.77 (95% CI=0.69, 0.85) for ≥ 7 hours/week relative to little or no exercise; the IRRs were reduced both among women with a healthy weight (BMI <25) at baseline and among women who were overweight (BMI 25-<30) at baseline. The IRRs for brisk walking for exercise and walking for transport were <1.0 for most levels of walking, but without clear trends of decreasing risk with increasing time spent walking.CONCLUSIONS:The results suggest that vigorous exercise may reduce the incidence of obesity among young African-American women. Results for brisk walking were inconclusive.