Perceived Interpersonal Racism in Relation to Incident Coronary Heart Disease Among Black Women.

BACKGROUND: Racism is highly prevalent in the United States. Few data exist about whether perceived interpersonal racism is associated with risk of coronary heart disease (CHD). METHODS: We followed 48 305 participants in the Black Women's Health Study through biennial mailed and Internet-based health questionnaires from 1997, when they provided information on perceived interpersonal racism and were free of cardiovascular disease and cancer, until the end of 2019. We averaged participant responses to 5 validated questions about perceived interpersonal racism in everyday activities, such as "people act as if they think you are dishonest." We summed the positive responses to 3 questions about perceived racism in interactions that involved jobs, housing, and police; scores ranged from 0 (no to all) to 3 (yes to all). CHD cases were defined as nonfatal myocardial infarctions confirmed through medical records, fatal cases identified through the National Death Index, and self-reported revascularization events. We used Cox proportional hazard models adjusting for major confounders to estimate hazard ratios (HRs). RESULTS: During 22 years of follow-up, we identified 1947 incident CHD cases. For women who reported experiences of racism in employment, housing, or involving the police relative to women who reported no such experiences, the age-adjusted HR for CHD was 1.35 (95% CI, 1.13-1.61; Ptrend=0.006), and the multivariable HR for CHD was 1.26 (95% CI, 1.05-1.51; Ptrend=0.05). For women in the highest quartile of perceived interpersonal racism in daily life relative to women in the lowest quartile, the age-adjusted HR for CHD was 1.25 (95% CI, 1.07-1.46; Ptrend=0.006). After multivariable adjustment, the HR was attenuated and no longer statistically significant. CONCLUSIONS: Perceived experiences of interpersonal racism in employment, in housing, and with the police were associated with higher incidence of CHD among Black women, whereas perceived racism in everyday life was not associated with higher risk.

A Population-Based Study of Genes Previously Implicated in Breast Cancer.

BACKGROUND: Population-based estimates of the risk of breast cancer associated with germline pathogenic variants in cancer-predisposition genes are critically needed for risk assessment and management in women with inherited pathogenic variants. METHODS: In a population-based case-control study, we performed sequencing using a custom multigene amplicon-based panel to identify germline pathogenic variants in 28 cancer-predisposition genes among 32,247 women with breast cancer (case patients) and 32,544 unaffected women (controls) from population-based studies in the Cancer Risk Estimates Related to Susceptibility (CARRIERS) consortium. Associations between pathogenic variants in each gene and the risk of breast cancer were assessed. RESULTS: Pathogenic variants in 12 established breast cancer-predisposition genes were detected in 5.03% of case patients and in 1.63% of controls. Pathogenic variants in BRCA1 and BRCA2 were associated with a high risk of breast cancer, with odds ratios of 7.62 (95% confidence interval [CI], 5.33 to 11.27) and 5.23 (95% CI, 4.09 to 6.77), respectively. Pathogenic variants in PALB2 were associated with a moderate risk (odds ratio, 3.83; 95% CI, 2.68 to 5.63). Pathogenic variants in BARD1, RAD51C, and RAD51D were associated with increased risks of estrogen receptor-negative breast cancer and triple-negative breast cancer, whereas pathogenic variants in ATM, CDH1, and CHEK2 were associated with an increased risk of estrogen receptor-positive breast cancer. Pathogenic variants in 16 candidate breast cancer-predisposition genes, including the c.657_661del5 founder pathogenic variant in NBN, were not associated with an increased risk of breast cancer. CONCLUSIONS: This study provides estimates of the prevalence and risk of breast cancer associated with pathogenic variants in known breast cancer-predisposition genes in the U.S. population. These estimates can inform cancer testing and screening and improve clinical management strategies for women in the general population with inherited pathogenic variants in these genes. (Funded by the National Institutes of Health and the Breast Cancer Research Foundation.).

Aspirin and nonaspirin nonsteroidal antiinflammatory drug use and occurrence of colorectal adenoma in Black American women.

Evidence suggests that aspirin use reduces the occurrence of colorectal neoplasia. Few studies have investigated the association among Black Americans, who are disproportionately burdened by the disease. We assessed aspirin use in relation to colorectal adenoma among Black women. The Black Women's Health Study is a prospective cohort of self-identified Black American women established in 1995. Participants reported regular aspirin use on baseline and follow-up questionnaires. Beginning in 1999, participants reported undergoing a colonoscopy or sigmoidoscopy, the only procedures through which colorectal adenomas can be diagnosed. Multivariable logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for associations between aspirin use and colorectal adenoma among 34 397 women who reported at least 1 colonoscopy or sigmoidoscopy. From 1997 through 2018, 1913 women were diagnosed with an adenoma. Compared to nonaspirin users, regular users had 14% (OR = 0.86, 95% CI: 0.78-0.95) lower odds of adenoma. The odds of adenoma decreased with increasing duration of aspirin use (≥10 years: OR = 0.80, 95% CI: 0.66-0.96). Initiating aspirin at a younger age was associated with a reduced adenoma occurrence (age < 40 years at initiation: OR = 0.69, 95% CI: 0.55-0.86). Regular aspirin use was associated with a decreased odds of colorectal adenoma in our study of Black women. These findings support evidence demonstrating a chemopreventive impact of aspirin on colorectal neoplasia and suggest that aspirin may be a useful prevention strategy among US Black women.

Research on Health Disparities: Strategies and Findings From the Black Women's Health Study.

The American Journal of Epidemiology has been a platform for findings from the Black Women's Health Study (BWHS) that are relevant to health disparities. Topics addressed have included methods of follow-up of a large cohort of Black women, disparities in health-care delivery, modifiable risk factors for health conditions that disproportionately affect Black women, associations with exposures that are highly prevalent in Black women, and methods for genetic research. BWHS papers have also highlighted the importance of considering social context, including perceived experiences of racism, in understanding health disparities. In the future, BWHS investigators will contribute to documentation of the role that structural racism plays in health disparities.

Menopausal hormone therapy use and risk of ovarian cancer by race: the ovarian cancer in women of African ancestry consortium.

BACKGROUND: Most studies examining post-menopausal menopausal hormone therapy (MHT) use and ovarian cancer risk have focused on White women and few have included Black women. METHODS: We evaluated MHT use and ovarian cancer risk in Black (n = 800 cases, 1783 controls) and White women (n = 2710 cases, 8556 controls), using data from the Ovarian Cancer in Women of African Ancestry consortium. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association of MHT use with ovarian cancer risk, examining histotype, MHT type and duration of use. RESULTS: Long-term MHT use, ≥10 years, was associated with an increased ovarian cancer risk for White women (OR = 1.38, 95%CI: 1.22-1.57) and the association was consistent for Black women (OR = 1.20, 95%CI: 0.81-1.78, pinteraction = 0.4). For White women, the associations between long-term unopposed estrogen or estrogen plus progesterone use and ovarian cancer risk were similar; the increased risk associated with long-term MHT use was confined to high-grade serous and endometroid tumors. Based on smaller numbers for Black women, the increased ovarian cancer risk associated with long-term MHT use was apparent for unopposed estrogen use and was predominately confined to other epithelial histotypes. CONCLUSION: The association between long-term MHT use and ovarian cancer risk was consistent for Black and White women.

Risk factors for endometrial cancer in Black women.

PURPOSE: The incidence of endometrial cancer (EC) has been increasing faster among Black women than among other racial/ethnic groups in the United States. Although the mortality rate is nearly twice as high among Black than White women, there is a paucity of literature on risk factors for EC among Black women, particularly regarding menopausal hormone use and severe obesity. METHODS: We pooled questionnaire data on 811 EC cases and 3,124 controls from eight studies with data on self-identified Black women (4 case-control and 4 cohort studies). We analyzed cohort studies as nested case-control studies with up to 4 controls selected per case. We used logistic regression to estimate multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: We observed a positive association between BMI and EC incidence (Ptrend < 0.0001) The OR comparing BMI ≥ 40 vs. < 25 kg/m2 was 3.92 (95% CI 2.91, 5.27). Abdominal obesity among those with BMI < 30 kg/m2 was not appreciably associated with EC risk (OR 1.21, 95% CI 0.74, 1.99). Associations of reproductive history with EC were similar to those observed in studies of White women. Long-term use of estrogen-only menopausal hormones was associated with an increased risk of EC (≥ 5 years vs. never use: OR 2.08, 95% CI: 1.06, 4.06). CONCLUSIONS: Our results suggest that the associations of established risk factors with EC are similar between Black and White women. Other explanations, such as differences in the prevalence of known risk factors or previously unidentified risk factors likely underlie the recent increases in EC incidence among Black women.

Hair relaxer use and risk of uterine cancer in the Black Women's Health Study.

BACKGROUND: Chemical hair relaxers, use of which is highly prevalent among Black women in the US, have been inconsistently linked to risk of estrogen-dependent cancers, such as breast cancer, and other reproductive health conditions. Whether hair relaxer use increases risk of uterine cancer is unknown. METHODS: In the Black Women's Health Study, 44,798 women with an intact uterus who self-identified as Black were followed from 1997, when chemical hair relaxer use was queried, until 2019. Over follow-up, 347 incident uterine cancers were diagnosed. We used multivariable Cox proportional hazards regression models, adjusted for age and other potential confounders, to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations of hair relaxer use with risk of uterine cancer. RESULTS: Compared to women who never used hair relaxers or used them infrequently (<4 years and ≤1-2 times/year), the HR for uterine cancer associated with heavy use (≥15 years and at least 5 times/year) was 1.18 (95% CI: 0.81, 1.71). However, among postmenopausal women, compared to never/light use, the HR for moderate use was 1.60 (95% CI: 1.01, 2.53), the HR for heavy use was 1.64 (1.01, 2.64), and the HR for ≥20 years of use regardless of frequency was 1.71 (1.08, 2.72). Results among premenopausal women were null. CONCLUSIONS: In this large cohort of Black women, long-term use of chemical hair relaxers was associated with increased risk of uterine cancer among postmenopausal women, but not among premenopausal women. These findings suggest that hair relaxer use may be a potentially modifiable risk factor for uterine cancer.

Sodium-containing acetaminophen and cardiovascular outcomes in individuals with and without hypertension.

AIMS: Previous studies have found high sodium intake to be associated with increased risks of cardiovascular disease (CVD) and all-cause mortality among individuals with hypertension; findings on the effect of intake among individuals without hypertension have been equivocal. We aimed to compare the risks of incident CVD and all-cause mortality among initiators of sodium-containing acetaminophen with the risk of initiators of non-sodium-containing formulations of the same drug according to the history of hypertension. METHODS AND RESULTS: Using The Health Improvement Network, we conducted two cohort studies among individuals with and without hypertension. We examined the relation of sodium-containing acetaminophen to the risk of each outcome during 1-year follow-up using marginal structural models with an inverse probability weighting to adjust for time-varying confounders. The outcomes were incident CVD (myocardial infarction, stroke, and heart failure) and all-cause mortality. Among individuals with hypertension (mean age: 73.4 years), 122 CVDs occurred among 4532 initiators of sodium-containing acetaminophen (1-year risk: 5.6%) and 3051 among 146 866 non-sodium-containing acetaminophen initiators (1-year risk: 4.6%). The average weighted hazard ratio (HR) was 1.59 [95% confidence interval (CI) 1.32-1.92]. Among individuals without hypertension (mean age: 71.0 years), 105 CVDs occurred among 5351 initiators of sodium-containing acetaminophen (1-year risk: 4.4%) and 2079 among 141 948 non-sodium-containing acetaminophen initiators (1-year risk: 3.7%), with an average weighted HR of 1.45 (95% CI 1.18-1.79). Results of specific CVD outcomes and all-cause mortality were similar. CONCLUSION: The initiation of sodium-containing acetaminophen was associated with increased risks of CVD and all-cause mortality among individuals with or without hypertension. Our findings suggest that individuals should avoid unnecessary excessive sodium intake through sodium-containing acetaminophen use.

Racial disparities in epithelial ovarian cancer survival: An examination of contributing factors in the Ovarian Cancer in Women of African Ancestry consortium.

Black women diagnosed with epithelial ovarian cancer have poorer survival compared to white women. Factors that contribute to this disparity, aside from socioeconomic status and guideline-adherent treatment, have not yet been clearly identified. We examined data from the Ovarian Cancer in Women of African Ancestry (OCWAA) consortium which harmonized data on 1074 Black women and 3263 white women with ovarian cancer from seven US studies. We selected potential mediators and confounders by examining associations between each variable with race and survival. We then conducted a sequential mediation analysis using an imputation method to estimate total, direct, and indirect effects of race on ovarian cancer survival. Black women had worse survival than white women (HR = 1.30; 95% CI 1.16-1.47) during study follow-up; 67.9% of Black women and 69.8% of white women died. In our final model, mediators of this disparity include college education, nulliparity, smoking status, body mass index, diabetes, diabetes/race interaction, postmenopausal hormone (PMH) therapy duration, PMH duration/race interaction, PMH duration/age interaction, histotype, and stage. These mediators explained 48.8% (SE = 12.1%) of the overall disparity; histotype/stage and PMH duration accounted for the largest fraction. In summary, nearly half of the disparity in ovarian cancer survival between Black and white women in the OCWAA consortium is explained by education, lifestyle factors, diabetes, PMH use, and tumor characteristics. Our findings suggest that several potentially modifiable factors play a role. Further research to uncover additional mediators, incorporate data on social determinants of health, and identify potential avenues of intervention to reduce this disparity is urgently needed.

Maximum and Time-Dependent Body Mass Index and Breast Cancer Incidence Among Postmenopausal Women in the Black Women's Health Study.

While excess weight is an established risk factor for postmenopausal breast cancer, consideration of maximum body mass index (maxBMI; BMI is calculated as weight (kg)/height (m)2) or BMI at a point in time relevant for breast carcinogenesis may offer new insights. We prospectively evaluated maxBMI and time-dependent BMI in relation to breast cancer incidence among 31,028 postmenopausal women in the Black Women's Health Study. During 1995-2015, a total of 1,384 diagnoses occurred, including 787 estrogen-receptor (ER)-positive (ER+) cases and 310 ER-negative (ER-) cases. BMI was assessed at baseline and 2, 4, 6, and 8 years before diagnosis. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Compared with women with BMI <25, those with BMI ≥35 had increased risk of ER+ breast cancer but not ER- breast cancer. For BMI assessed 2 years before diagnosis, the HRs for ER+ breast cancer associated with maxBMI ≥35 and time-dependent BMI ≥35 were 1.42 (95% confidence interval (CI): 1.10, 1.84) and 1.63 (95% CI: 1.25, 2.13), respectively. The corresponding HR for time-dependent BMI assessed 6 years before diagnosis was 1.95 (95% CI: 1.45, 2.62). These findings suggest strong associations of BMI with risk of ER+ breast cancer in postmenopausal women, regardless of timing of BMI assessment.

Racial differences in the association of body mass index and ovarian cancer risk in the OCWAA Consortium.

BACKGROUND: Obesity disproportionately affects African American (AA) women and has been shown to increase ovarian cancer risk, with some suggestions that the association may differ by race. METHODS: We evaluated body mass index (BMI) and invasive epithelial ovarian cancer (EOC) risk in a pooled study of case-control and nested case-control studies including AA and White women. We evaluated both young adult and recent BMI (within the last 5 years). Associations were estimated using multi-level and multinomial logistic regression models. RESULTS: The sample included 1078 AA cases, 2582 AA controls, 3240 White cases and 9851 White controls. We observed a higher risk for the non-high-grade serous (NHGS) histotypes for AA women with obesity (ORBMI 30+= 1.62, 95% CI: 1.16, 2.26) and White women with obesity (ORBMI 30+= 1.20, 95% CI: 1.02, 2.42) compared to non-obese. Obesity was associated with higher NHGS risk in White women who never used HT (ORBMI 30+= 1.40, 95% CI: 1.08, 1.82). Higher NHGS ovarian cancer risk was observed for AA women who ever used HT (ORBMI 30+= 2.66, 95% CI: 1.15, 6.13), while in White women, there was an inverse association between recent BMI and risk of EOC and HGS in ever-HT users (EOC ORBMI 30+= 0.81, 95% CI: 0.69, 0.95, HGS ORBMI 30+= 0.73, 95% CI: 0.61, 0.88). CONCLUSION: Obesity contributes to NHGS EOC risk in AA and White women, but risk across racial groups studied differs by HT use and histotype.

Admixture mapping of anthropometric traits in the Black Women's Health Study: evidence of a shared African ancestry component with birth weight and type 2 diabetes.

Prevalence of obesity, type 2 diabetes (T2D), and being born with low birth weight are much higher in African American women compared to U.S. white women. Genetic factors may contribute to the excess risk of these conditions. We conducted admixture mapping of body mass index (BMI) at age 18, adult BMI, and adult waist circumference and waist-to-hip ratio adjusted for BMI using 2918 ancestral informative markers in 2596 participants of the Black Women's Health Study. We also searched for evidence of shared African genetic ancestry components among the four examined anthropometric traits and among birth weight and T2D. We found that global percent African ancestry was associated with higher adult BMI. We also found that African ancestry at 9q34 was associated with lower BMI at age 18. Our shared ancestry analysis identified ten genomic regions with local African ancestry associated with multiple traits. Seven out of these ten genomic loci were related to T2D risk. Of special interest is the 12q14-21 region where local African ancestry was associated with low birth weight, low BMI, high BMI-adjusted waist-to-hip ratio, and high T2D risk. Findings in the 12q14-21 genomic locus are consistent with the fetal insulin hypothesis that postulates that low birth weight and T2D have a common genetic basis, and they support the hypothesis of a shared African genetic ancestry component linking low birth weight and T2D in African Americans. Future studies should identify the actual genetic variants responsible for the clustering of these conditions in African Americans.

A Prospective Analysis of Red and Processed Meat Intake in Relation to Colorectal Cancer in the Black Women's Health Study.

BACKGROUND: Black Americans have the highest incidence of colorectal cancer (CRC) of any racial/ethnic group in the United States. High intake of red and processed meats has been associated with an increased CRC risk in predominately White populations. However, 3 prior studies in Black populations, who have been reported to have high intakes of red and processed meats, have reported no associations. Data on a possible association between CRC risk and SFAs and MUFAs, the primary types of fat in red and processed meats, are inconclusive. OBJECTIVES: We prospectively assessed intakes of processed and unprocessed red meat, SFAs, and MUFAs in relation to CRC risk, utilizing data from the Black Women's Health Study (BWHS, 1995-2018). METHODS: Dietary data were derived from validated FFQs completed in 1995 and 2001. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression. RESULTS: Among 52,695 BWHS participants aged 21-69 y at baseline and followed for ≤22 y, 564 women developed incident CRC. Unprocessed red meat intake was associated with a 33% increased CRC risk per 100 g/d (HR: 1.33; 95% CI: 1.03-1.71). Examination of CRC anatomic sites revealed that unprocessed red meat was associated with 2-times increased rectal cancer risk (HR: 2.22; 95% CI: 1.15-4.26). There was no evidence of an interaction with age (pinteraction = 0.4), but unprocessed red meat intake was only associated with a significant increased risk of late-onset CRC (≥50 y of age, HR: 1.41; 95% CI: 1.05-1.88). Processed red meat and total SFA and MUFA intakes were not associated with CRC risk. CONCLUSIONS: Unprocessed red meat intake was associated with an increased CRC risk in the present study, the first positive evidence that red meat plays a role in the etiology of CRC in Black women. The findings suggest prevention opportunities.

A population-based psychometric analysis of the insomnia severity index in black women with and without a history of cancer.

Black women are under-represented in insomnia research. Further, cancer treatments increase the risk of late effects, thus affecting the sleep of psychologically and medically vulnerable cancer survivors. The Insomnia Severity Index (ISI) is widely used, but has not been researched in black women, and research in cancer survivors is limited. Prior studies demonstrate that psychometric properties of the ISI are not consistent across samples. This study examined the internal consistency and factor structure of the ISI in 29,500 participants from the Black Women's Health Study, an epidemiological study of black women in the United States. This cohort included 28,214 women without a cancer history and 1,286 cancer survivors. Exploratory, confirmatory and multigroup analyses were conducted to determine the psychometric properties of the ISI in these groups. The mean ISI score was 7.18 (standard deviation [SD] = 6.82). Findings supported the internal consistency reliability of the ISI in black women with (Ω = 0.896) and without (Ω = 0.892) a cancer history. Exploratory factor analyses supported a one-factor structure. Confirmatory factor analyses indicated that fit of this one-factor model was not robust in survivors (Satorra-Bentler chi-square [χSB2 (14)] = 197.78, comparative fit index [CFI] = 0.928, root mean-square error of approximation [RMSEA] = 0.143) or in women with no cancer history (χSB2 (14) = 2,887.93, CFI = 0.945, RMSEA = 0.121), but the alternative models we examined were not superior. Although factor structures in previous studies have varied considerably, we found a one-factor structure. Although internal consistency reliability was strong, factor analytic results did not further support the ISI. Inconsistencies in ISI measurement properties across studies may reflect differences in sample sizes and populations.

Hair product use and breast cancer incidence in the Black Women's Health Study.

Hair relaxers and leave-in conditioners and oils, commonly used by Black/African American women, may contain estrogens or estrogen-disrupting compounds. Thus, their use may contribute to breast cancer risk. Results of the few previous studies on this topic are inconsistent. We assessed the relation of hair relaxer and leave-in conditioner use to breast cancer incidence in the Black Women's Health Study, a nationwide prospective study of Black women. Among 50 543 women followed from 1997 to 2017, 2311 incident breast cancers occurred. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression for breast cancer overall and by estrogen receptor (ER) status. For heavy use (≥15 years of use for ≥7 times/year) of hair relaxers relative to never/light use (<4 years, no more than 1-2 times/year), the multivariable HR for breast cancer overall was 1.13 (95%CI: 0.96-1.33). Duration, frequency, age at first use and number of scalp burns were not associated with overall breast cancer risk. For heavy use of hair relaxers containing lye, the corresponding HR for ER+ breast cancer was 1.32 (95% CI: 0.97, 1.80); there was no association for non-lye products. There was no association of conditioner use and breast cancer. Results of this study were largely null, but there was some evidence that heavy use of lye-containing hair relaxers may be associated with increased risk of ER+ breast cancer. Consistent results from several studies are needed before it can be concluded that use of certain hair relaxers impacts breast cancer development.

Neighborhood disadvantage and individual-level life stressors in relation to breast cancer incidence in US Black women.

BACKGROUND: Research on psychosocial stress and risk of breast cancer has produced conflicting results. Few studies have assessed this relation by breast cancer subtype or specifically among Black women, who experience unique chronic stressors. METHODS: We used prospective data from the Black Women's Health Study, an ongoing cohort study of 59,000 US Black women, to assess neighborhood- and individual-level psychosocial factors in relation to risk of breast cancer. We used factor analysis to derive two neighborhood score variables after linking participant addresses to US Census data (2000 and 2010) on education, employment, income and poverty, female-headed households, and Black race for all households in each residential block group. We used Cox proportional hazards regression to estimate hazard ratios (HR) and 95% confidence intervals (CI) adjusted for established breast cancer risk factors. RESULTS: During follow-up from 1995 to 2017, there were 2167 incident invasive breast cancer cases (1259 estrogen receptor positive (ER +); 687 ER negative (ER-)). For ER- breast cancer, HRs were 1.26 (95% CI 1.00-1.58) for women living in the highest quartile of neighborhood disadvantage relative to women in the lowest quartile, and 1.24 (95% CI 0.98-1.57) for lowest versus highest quartile of neighborhood socioeconomic status (SES). For ER+ breast cancer, living in the lowest quartile of neighborhood SES was associated with a reduced risk of ER+ breast cancer (HR = 0.83, 95% CI 0.70-0.98). With respect to individual-level factors, childhood sexual abuse (sexual assault ≥ 4 times vs. no abuse: HR = 1.35, 95% CI 1.01-1.79) and marital status (married/living together vs. single: HR = 1.29, 95% CI 1.08-1.53) were associated with higher risk of ER+, but not ER- breast cancer. CONCLUSION: Neighborhood disadvantage and lower neighborhood SES were associated with an approximately 25% increased risk of ER- breast cancer in this large cohort of Black women, even after control for multiple behaviors and lifestyle factors. Further research is need to understand the underlying reasons for these associations. Possible contributing factors are biologic responses to the chronic stress/distress experienced by individuals who reside in neighborhoods characterized by high levels of noise, crime and unemployment or the direct effects of environmental toxins.

First- and second-degree family history of ovarian and breast cancer in relation to risk of invasive ovarian cancer in African American and white women.

Family history (FH) of ovarian cancer and breast cancer are well-established risk factors for ovarian cancer, but few studies have examined this association in African American (AA) and white women by histotype. We assessed first- and second-degree FH of ovarian and breast cancer and risk of epithelial ovarian cancer in the Ovarian Cancer in Women of African Ancestry Consortium. Analyses included 1052 AA cases, 2328 AA controls, 2380 white cases and 3982 white controls. Race-specific odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multilevel logistic regression with adjustment for covariates. Analyses were stratified by histotype (high-grade serous vs others). First-degree FH of ovarian cancer was associated with high-grade serous carcinoma in AA (OR = 2.32, 95% CI: 1.50, 3.59) and white women (OR = 2.48, 95% CI: 1.82, 3.38). First-degree FH of breast cancer increased risk irrespective of histotype in AAs, but with high-grade serous carcinoma only in white women. Associations with second-degree FH of ovarian cancer were observed for overall ovarian cancer in white women and with high-grade serous carcinoma in both groups. First-degree FH of ovarian cancer and of breast cancer, and second-degree FH of ovarian cancer is strongly associated with high-grade serous ovarian carcinoma in AA and white women. The association of FH of breast cancer with high-grade serous ovarian carcinoma is similar in white women and AA women, but may differ for other histotypes.

Associations Between Prediagnostic Concentrations of Circulating Sex Steroid Hormones and Liver Cancer Among Postmenopausal Women.

BACKGROUND AND AIMS: In almost all countries, incidence rates of liver cancer (LC) are 100%-200% higher in males than in females. However, this difference is predominantly driven by hepatocellular carcinoma (HCC), which accounts for 75% of LC cases. Intrahepatic cholangiocarcinoma (ICC) accounts for 12% of cases and has rates only 30% higher in males. Hormones are hypothesized to underlie observed sex differences. We investigated whether prediagnostic circulating hormone and sex hormone binding globulin (SHBG) levels were associated with LC risk, overall and by histology, by leveraging resources from five prospective cohorts. APPROACH AND RESULTS: Seven sex steroid hormones and SHBG were quantitated using gas chromatography/tandem mass spectrometry and competitive electrochemiluminescence immunoassay, respectively, from baseline serum/plasma samples of 191 postmenopausal female LC cases (HCC, n = 83; ICC, n = 56) and 426 controls, matched on sex, cohort, age, race/ethnicity, and blood collection date. Odds ratios (ORs) and 95% confidence intervals (CIs) for associations between a one-unit increase in log2 hormone value (approximate doubling of circulating concentration) and LC were calculated using multivariable-adjusted conditional logistic regression. A doubling in the concentration of 4-androstenedione (4-dione) was associated with a 50% decreased LC risk (OR = 0.50; 95% CI = 0.30-0.82), whereas SHBG was associated with a 31% increased risk (OR = 1.31; 95% CI = 1.05-1.63). Examining histology, a doubling of estradiol was associated with a 40% increased risk of ICC (OR = 1.40; 95% CI = 1.05-1.89), but not HCC (OR = 1.12; 95% CI = 0.81-1.54). CONCLUSIONS: This study provides evidence that higher levels of 4-dione may be associated with lower, and SHBG with higher, LC risk in women. However, this study does not support the hypothesis that higher estrogen levels decrease LC risk. Indeed, estradiol may be associated with an increased ICC risk.

A prospective cohort study of ambient air pollution exposure and risk of uterine leiomyomata.

STUDY QUESTION: To what extent are ambient concentrations of particulate matter <2.5 microns (PM2.5), nitrogen dioxide (NO2) and ozone (O3) associated with risk of self-reported physician-diagnosed uterine leiomyomata (UL)? SUMMARY ANSWER: In this large prospective cohort study of Black women, ambient concentrations of O3, but not PM2.5 or NO2, were associated with increased risk of UL. WHAT IS KNOWN ALREADY: UL are benign tumors of the myometrium that are the leading cause of gynecologic inpatient care among reproductive-aged women. Black women are clinically diagnosed at two to three times the rate of white women and tend to exhibit earlier onset and more severe disease. Two epidemiologic studies have found positive associations between air pollution exposure and UL risk, but neither included large numbers of Black women. STUDY DESIGN, SIZE, DURATION: We conducted a prospective cohort study of 21 998 premenopausal Black women residing in 56 US metropolitan areas from 1997 to 2011. PARTICIPANTS/MATERIAL, SETTING, METHODS: Women reported incident UL diagnosis and method of confirmation (i.e. ultrasound, surgery) on biennial follow-up questionnaires. We modeled annual residential concentrations of PM2.5, NO2 and O3 throughout the study period. We used Cox proportional hazards regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for a one-interquartile range (IQR) increase in air pollutant concentrations, adjusting for confounders and co-pollutants. MAIN RESULTS AND THE ROLE OF CHANCE: During 196 685 person-years of follow-up, 6238 participants (28.4%) reported physician-diagnosed UL confirmed by ultrasound or surgery. Although concentrations of PM2.5 and NO2 were not appreciably associated with UL (HRs for a one-IQR increase: 1.01 (95% CI: 0.93, 1.10) and 1.05 (95% CI: 0.95, 1.16), respectively), O3 concentrations were associated with increased UL risk (HR for a one-IQR increase: 1.19, 95% CI: 1.07, 1.32). The association was stronger among women age <35 years (HR: 1.26, 95% CI: 0.98, 1.62) and parous women (HR: 1.28, 95% CI: 1.11, 1.48). LIMITATIONS, REASONS FOR CAUTION: Our measurement of air pollution is subject to misclassification, as monitoring data are not equally spatially distributed and we did not account for time-activity patterns. Our outcome measure was based on self-report of a physician diagnosis, likely resulting in under-ascertainment of UL. Although we controlled for several individual- and neighborhood-level confounding variables, residual confounding remains a possibility. WIDER IMPLICATIONS OF THE FINDINGS: Inequitable burden of air pollution exposure has important implications for racial health disparities, and may be related to disparities in UL. Our results emphasize the need for additional research focused on environmental causes of UL. STUDY FUNDING/COMPETING INTEREST(S): This research was funded by the National Cancer Institute (U01-CAA164974) and the National Institute of Environmental Health Sciences (R01-ES019573). L.A.W. is a fibroid consultant for AbbVie, Inc. and accepts in-kind donations from Swiss Precision Diagnostics, Sandstone Diagnostics, FertilityFriend.com and Kindara.com for primary data collection in Pregnancy Study Online (PRESTO). M.J. declares consultancy fees from the Health Effects Institute (as a member of the review committee). The remaining authors declare they have no actual or potential competing financial interests. TRIAL REGISTRATION NUMBER: N/A.

Dietary Vitamin A and Breast Cancer Risk in Black Women: The African American Breast Cancer Epidemiology and Risk (AMBER) Consortium.

BACKGROUND: Studies in women of European descent showed an inverse association of dietary vitamin A (retinol and carotenoids) intake with breast cancer risks, mainly in premenopausal women. OBJECTIVES: We examined whether higher compared with lower levels of dietary vitamin A are associated with reduced breast cancer risks among Black women by estrogen receptor (ER) and menopausal statuses. METHODS: In this pooled analysis, data were from 3564 breast cancer cases and 11,843 controls (mean ages = 56.4 and 56.3 years, respectively) in the African American Breast Cancer Epidemiology and Risk (AMBER) Consortium. Dietary intake was assessed by FFQs. Multivariable logistic regressions were performed to estimate ORs and 95% CIs for study-specific quintiles of total vitamin A equivalents and individual carotenoids, and a pooled OR was estimated by a random-effect model. RESULTS: We observed an inverse association of total vitamin A equivalents with ER-positive breast cancer (quintiles 5 compared with 1: pooled OR: 0.82; 95% CI: 0.67-1.00; P-trend = 0.045). The association was seen among premenopausal women (pooled OR: 0.60; 95% CI: 0.43-0.83; P-trend = 0.004), but not among postmenopausal women (pooled OR: 0.99; 95% CI: 0.77-1.28; P-trend = 0.78). Additionally, there were inverse associations of dietary ß-carotene (quintiles 5 compared with 1: pooled OR: 0.70; 95% CI: 0.51-0.95; P-trend = 0.08) and lutein (pooled OR: 0.63; 95% CI: 0.45-0.87; P-trend = 0.020) with ER-positive breast cancer among premenopausal women. There was no evidence for an association of total vitamin A equivalents or individual carotenoids with ER-negative breast cancer, regardless of menopausal status. CONCLUSIONS: Our findings on dietary vitamin A and breast cancer risks in Black women are consistent with observations in women of European descent and advance the literature showing an inverse association for ER-positive disease.