Publications by authors named "Julie R Palmer"

310 Publications

A Validated Risk Prediction Model for Breast Cancer in US Black Women.

J Clin Oncol 2021 Oct 8:JCO2101236. Epub 2021 Oct 8.

Boston University School of Public Health, Boston, MA.

Purpose: Breast cancer risk prediction models are used to identify high-risk women for early detection, targeted interventions, and enrollment into prevention trials. We sought to develop and evaluate a risk prediction model for breast cancer in US Black women, suitable for use in primary care settings.

Methods: Breast cancer relative risks and attributable risks were estimated using data from Black women in three US population-based case-control studies (3,468 breast cancer cases; 3,578 controls age 30-69 years) and combined with SEER age- and race-specific incidence rates, with incorporation of competing mortality, to develop an absolute risk model. The model was validated in prospective data among 51,798 participants of the Black Women's Health Study, including 1,515 who developed invasive breast cancer. A second risk prediction model was developed on the basis of estrogen receptor (ER)-specific relative risks and attributable risks. Model performance was assessed by calibration (expected/observed cases) and discriminatory accuracy (C-statistic).

Results: The expected/observed ratio was 1.01 (95% CI, 0.95 to 1.07). Age-adjusted C-statistics were 0.58 (95% CI, 0.56 to 0.59) overall and 0.63 (95% CI, 0.58 to 0.68) among women younger than 40 years. These measures were almost identical in the model based on estrogen receptor-specific relative risks and attributable risks.

Conclusion: Discriminatory accuracy of the new model was similar to that of the most frequently used questionnaire-based breast cancer risk prediction models in White women, suggesting that effective risk stratification for Black women is now possible. This model may be especially valuable for risk stratification of young Black women, who are below the ages at which breast cancer screening is typically begun.
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http://dx.doi.org/10.1200/JCO.21.01236DOI Listing
October 2021

Predicted Vitamin D Status and Colorectal Cancer Incidence in the Black Women's Health Study.

Cancer Epidemiol Biomarkers Prev 2021 Oct 7. Epub 2021 Oct 7.

Slone Epidemiology Center at Boston University, Boston, Massachusetts.

Background: Observational studies, mostly among White populations, suggest that low vitamin D levels increase colorectal cancer risk. African Americans, who are disproportionately burdened by colorectal cancer, often have lower vitamin D levels compared with other populations.

Methods: We assessed predicted vitamin D score in relation to colorectal cancer among 49,534 participants in the Black Women's Health Study, a cohort of African American women followed from 1995 to 2017 through biennial questionnaires. We derived predicted vitamin D scores at each questionnaire cycle for all participants using a previously validated prediction model based on actual 25-hydroxyvitamin D values from a subset of participants. We calculated cumulative average predicted vitamin D score at every cycle by averaging scores from cycles up to and including that cycle. Using Cox proportional hazards regression, we estimated hazard ratios (HR) and 95% confidence intervals (CI) for colorectal cancer incidence according to predicted score quartiles.

Results: Over follow-up, 488 incident colorectal cancers occurred. Compared with women in the highest quartile of predicted vitamin D score, those in the lowest had an estimated 41% (HR = 1.41; 95% CI, 1.05-1.90) higher colorectal cancer risk. Comparable HRs were 1.44 (95% CI, 1.02-2.01) for colon and 1.34 (95% CI, 0.70-2.56) for rectal cancer.

Conclusions: Low vitamin D status may lead to elevated colorectal cancer risk in African American women.

Impact: Our findings, taken together with established evidence that vitamin D levels are generally lower in African Americans than other U.S. groups, suggest that low vitamin D status may contribute to the disproportionately high colorectal cancer incidence among African Americans.
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http://dx.doi.org/10.1158/1055-9965.EPI-21-0675DOI Listing
October 2021

Racial Disparities and Sex Differences in Early- and Late-Onset Colorectal Cancer Incidence, 2001-2018.

Front Oncol 2021 9;11:734998. Epub 2021 Sep 9.

Slone Epidemiology Center at Boston University, Boston, MA, United States.

Background: Colorectal cancer (CRC) incidence rates have increased in younger individuals worldwide. We examined the most recent early- and late-onset CRC rates for the US.

Methods: Age-standardized incidence rates (ASIR, per 100,000) of CRC were calculated using the US Cancer Statistics Database's high-quality population-based cancer registry data from the entire US population. Results were cross-classified by age (20-49 [early-onset] and 50-74 years [late-onset]), race/ethnicity (non-Hispanic White, non-Hispanic Black, Hispanic, American Indian/Alaskan Native, Asian/Pacific Islander), sex, anatomic location (proximal, distal, rectal), and histology (adenocarcinoma, neuroendocrine).

Results: During 2001 through 2018, early-onset CRC rates significantly increased among American Indians/Alaskan Natives, Hispanics, and Whites. Compared to Whites, early-onset CRC rates are now 21% higher in American Indians/Alaskan Natives and 6% higher in Blacks. Rates of early-onset colorectal neuroendocrine tumors have increased in Whites, Blacks, and Hispanics; early-onset colorectal neuroendocrine tumor rates are 2-times higher in Blacks compared to Whites. Late-onset colorectal adenocarcinoma rates are decreasing, while late-onset colorectal neuroendocrine tumor rates are increasing, in all racial/ethnic groups. Late-onset CRC rates remain 29% higher in Blacks and 15% higher in American Indians/Alaskan Natives compared to Whites. Overall, CRC incidence was higher in men than women, but incidence of early-onset distal colon cancer was higher in women.

Conclusions: The early-onset CRC disparity between Blacks and Whites has decreased, due to increasing rates in Whites-rates in Blacks have remained stable. However, rates of colorectal neuroendocrine tumors are increasing in Blacks. Blacks and American Indians/Alaskan Natives have the highest rates of both early- and late-onset CRC.

Impact: Ongoing prevention efforts must ensure access to and uptake of CRC screening for Blacks and American Indians/Alaskan Natives.
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http://dx.doi.org/10.3389/fonc.2021.734998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8459723PMC
September 2021

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

J Nutr 2021 Sep 7. Epub 2021 Sep 7.

Department of Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.

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 β-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.
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http://dx.doi.org/10.1093/jn/nxab278DOI Listing
September 2021

Discovery of structural deletions in breast cancer predisposition genes using whole genome sequencing data from > 2000 women of African-ancestry.

Hum Genet 2021 Oct 27;140(10):1449-1457. Epub 2021 Aug 27.

Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, TN, 37203-1738, Nashville, USA.

Single germline nucleotide pathogenic variants have been identified in 12 breast cancer predisposition genes, but structural deletions in these genes remain poorly characterized. We conducted in-depth whole genome sequencing (WGS) in genomic DNA samples obtained from 1340 invasive breast cancer cases and 675 controls of African ancestry. We identified 25 deletions in the intragenic regions of ten established breast cancer predisposition genes based on a consensus call from six state-of-the-art SV callers. Overall, no significant case-control difference was found in the frequency of these deletions. However, 1.0% of cases and 0.3% of controls carried any of the eight putative protein-truncating rare deletions located in BRCA1, BRCA2, CDH1, TP53, NF1, RAD51D, RAD51C and CHEK2, resulting in an odds ratio (OR) of 3.29 (95% CI 0.74-30.16). We also identified a low-frequency deletion in NF1 associated with breast cancer risk (OR 1.93, 95% CI 1.14-3.42). In addition, we detected 56 deletions, including six putative protein-truncating deletions, in suspected breast predisposition genes. This is the first large study to systematically search for structural deletions in breast cancer predisposition genes. Many of the deletions, particularly those resulting in protein truncations, are likely to be pathogenic. Results from this study, if confirmed in future large-scale studies, could have significant implications for genetic testing for this common cancer.
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http://dx.doi.org/10.1007/s00439-021-02342-8DOI Listing
October 2021

"The Study on Stress, Spirituality, and Health (SSSH): Psychometric Evaluation and Initial Validation of the SSSH Baseline Spirituality Survey".

Religions (Basel) 2021 Mar 25;12(3). Epub 2021 Feb 25.

Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.

This paper describes the development and initial psychometric testing of the baseline Spirituality Survey (SS-1) from the Study on Stress, Spirituality, and Health (SSSH) which contained a mixture of items selected from validated existing scales and new items generated to measure important constructs not captured by existing instruments. The purpose was to establish the validity of new and existing measures in our racially/ethnically diverse sample. Psychometric properties of the SS-1 were evaluated using standard psychometric analyses in 4,634 SSSH participants. Predictive validity of SS-1 scales was assessed in relation to the physical and mental health component scores from the Short-Form 12 Health Survey (SF-12). Scales exhibited adequate to strong psychometric properties and demonstrated construct and predictive validity. Overall, the correlational findings provide solid evidence that the SS-1 scales are associated with a wide range of relevant R/S attitudes, mental health, and to a lesser degree physical health.
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http://dx.doi.org/10.3390/rel12030150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415767PMC
March 2021

Gestational diabetes and risk of breast cancer before age 55 years.

Int J Epidemiol 2021 Aug 29. Epub 2021 Aug 29.

Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Durham, NC, USA.

Background: The history of gestational diabetes mellitus (GDM) has been associated with breast cancer risk in some studies, particularly in young women, but results of cohort studies are conflicting.

Methods: We pooled data from 257 290 young (age <55 years) women from five cohorts. We used multivariable Cox proportional-hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between GDM history and risk of breast cancer, overall and by oestrogen receptor (ER) status, before age 55 years, adjusted for established breast cancer risk factors.

Results: Five percent of women reported a history of GDM and 6842 women reported an incident breast-cancer diagnosis (median follow-up = 16 years; maximum = 24 years). Compared with parous women without GDM, women with a history of GDM were not at increased risk of young-onset breast cancer overall (HR = 0.90; 95% CI: 0.78, 1.03) or by ER status (HR = 0.96; 95% CI: 0.79, 1.16 for ER-positive; HR = 1.07; 95% CI: 0.78, 1.47 for ER-negative). Compared with nulliparous women, parous women with a history of GDM had a lower risk of breast cancer overall (HR = 0.79; 95% CI: 0.68, 0.91) and of ER-positive (HR = 0.82; 95% CI: 0.66, 1.02) but not ER-negative (HR = 1.09; 95% CI: 0.76, 1.54) invasive breast cancer. These results were consistent with the HRs comparing parous women without GDM to nulliparous women.

Conclusions: Results of this analysis do not support the hypothesis that GDM is a risk factor for breast cancer in young women. Our findings suggest that the well-established protective effect of parity on risk of ER-positive breast cancer persists even for pregnancies complicated by GDM.
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http://dx.doi.org/10.1093/ije/dyab165DOI Listing
August 2021

Lower serum 25(OH)D levels associated with higher risk of COVID-19 infection in U.S. Black women.

PLoS One 2021 27;16(7):e0255132. Epub 2021 Jul 27.

Slone Epidemiology Center at Boston University, Boston, Massachusetts, United States of America.

Objective: Limited evidence suggests that higher levels of serum vitamin D (25(OH)D) protect against SARS-CoV-2 virus (COVID-19) infection. Black women commonly experience 25(OH)D insufficiency and are overrepresented among COVID-19 cases. We conducted a prospective analysis of serum 25(OH)D levels in relation to COVID-19 infection among participants in the Black Women's Health Study.

Methods: Since 1995, the Black Women's Health Study has followed 59,000 U.S. Black women through biennial mailed or online questionnaires. Over 13,000 study participants provided a blood sample in 2013-2017. 25(OH)D assays were performed in a certified national laboratory shortly after collection of the samples. In 2020, participants who had completed the online version of the 2019 biennial health questionnaire were invited to complete a supplemental online questionnaire assessing their experiences related to the COVID-19 pandemic, including whether they had been tested for COVID-19 infection and the result of the test. We used logistic regression analysis to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association of 25(OH)D level with COVID-19 positivity, adjusting for age, number of people living in the household, neighborhood socioeconomic status, and other potential confounders.

Results: Among 5,081 eligible participants whose blood sample had been assayed for 25(OH)D, 1,974 reported having had a COVID-19 test in 2020. Relative to women with 25(OH)D levels of 30 ng/mL (75 nmol/l) or more, multivariable-adjusted ORs for COVID-19 infection in women with levels of 20-29 ng/mL (50-72.5 nmol/l) and <20 ng/mL (<50 nmol/l) were, respectively, 1.48 (95% CI 0.95-2.30) and 1.69 (95% CI 1.04-2.72) (p trend 0.02).

Conclusion: The present results suggest that U.S. Black women with lower levels of 25(OH)D are at increased risk of infection with COVID-19. Further work is needed to confirm these findings and determine the optimal level of 25(OH)D for a beneficial effect.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0255132PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315514PMC
August 2021

Race, ethnicity, community-level socioeconomic factors, and risk of COVID-19 in the United States and the United Kingdom.

EClinicalMedicine 2021 Aug 17;38:101029. Epub 2021 Jul 17.

Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, 100 Cambridge Street, 15th Floor, Boston, MA 02114, USA.

Background: There is limited prior investigation of the combined influence of personal and community-level socioeconomic factors on racial/ethnic disparities in individual risk of coronavirus disease 2019 (COVID-19).

Methods: We performed a cross-sectional analysis nested within a prospective cohort of 2,102,364 participants from March 29, 2020 in the United States (US) and March 24, 2020 in the United Kingdom (UK) through December 02, 2020 via the COVID Symptom Study smartphone application. We examined the contribution of community-level deprivation using the Neighborhood Deprivation Index (NDI) and the Index of Multiple Deprivation (IMD) to observe racial/ethnic disparities in COVID-19 incidence. ClinicalTrials.gov registration: NCT04331509.

Findings: Compared with non-Hispanic White participants, the risk for a positive COVID-19 test was increased in the US for non-Hispanic Black (multivariable-adjusted odds ratio [OR], 1.32; 95% confidence interval [CI], 1.18-1.47) and Hispanic participants (OR, 1.42; 95% CI, 1.33-1.52) and in the UK for Black (OR, 1.17; 95% CI, 1.02-1.34), South Asian (OR, 1.39; 95% CI, 1.30-1.49), and Middle Eastern participants (OR, 1.38; 95% CI, 1.18-1.61). This elevated risk was associated with living in more deprived communities according to the NDI/IMD. After accounting for downstream mediators of COVID-19 risk, community-level deprivation still mediated 16.6% and 7.7% of the excess risk in Black compared to White participants in the US and the UK, respectively.

Interpretation: Our results illustrate the critical role of social determinants of health in the disproportionate COVID-19 risk experienced by racial and ethnic minorities.
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http://dx.doi.org/10.1016/j.eclinm.2021.101029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285255PMC
August 2021

Risk of Late-Onset Breast Cancer in Genetically Predisposed Women.

J Clin Oncol 2021 Jul 22:JCO2100531. Epub 2021 Jul 22.

Fred Hutchinson Cancer Research Center, Seattle, WA.

Purpose: The prevalence of germline pathogenic variants (PVs) in established breast cancer predisposition genes in women in the general population over age 65 years is not well-defined. However, testing guidelines suggest that women diagnosed with breast cancer over age 65 years might have < 2.5% likelihood of a PV in a high-penetrance gene. This study aimed to establish the frequency of PVs and remaining risks of breast cancer for each gene in women over age 65 years.

Methods: A total of 26,707 women over age 65 years from population-based studies (51.5% with breast cancer and 48.5% unaffected) were tested for PVs in germline predisposition gene. Frequencies of PVs and associations between PVs in each gene and breast cancer were assessed, and remaining lifetime breast cancer risks were estimated for non-Hispanic White women with PVs.

Results: The frequency of PVs in predisposition genes was 3.18% for women with breast cancer and 1.48% for unaffected women over age 65 years. PVs in , , and were found in 3.42% of women diagnosed with estrogen receptor (ER)-negative, 1.0% with ER-positive, and 3.01% with triple-negative breast cancer. Frequencies of PVs were lower among women with no first-degree relatives with breast cancer. PVs in , , , and were associated with increased risks (odds ratio = 2.9-4.0) of breast cancer. Remaining lifetime risks of breast cancer were ≥ 15% for those with PVs in , , and .

Conclusion: This study suggests that all women diagnosed with triple-negative breast cancer or ER-negative breast cancer should receive genetic testing and that women over age 65 years with and PVs and perhaps with and PVs should be considered for magnetic resonance imaging screening.
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http://dx.doi.org/10.1200/JCO.21.00531DOI Listing
July 2021

Prenatal Diethylstilbestrol Exposure and Cancer Risk in Males.

Cancer Epidemiol Biomarkers Prev 2021 Oct 16;30(10):1826-1833. Epub 2021 Jul 16.

Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.

Background: The influence of prenatal diethylstilbestrol (DES) exposure on cancer incidence among middle-aged men has not been well-characterized. We investigated whether exposure to DES before birth impacts overall cancer risk, and risk of site-specific cancers.

Methods: Men (mean age in 2016 = 62.0 years) who were or were not prenatally DES exposed were identified between 1953 and 1994 and followed for cancer primarily via questionnaire approximately every 5 years between 1994 and 2016. The overall and site-specific cancer rates of the two groups were compared using Poisson regression and proportional hazards modeling with adjustment for age.

Results: DES exposure was not associated with either overall cancer [hazard ratio (HR), 0.94; 95% confidence interval (CI), 0.77-1.15] or total prostate cancer rates (HR, 0.95; 95% CI, 0.68-1.33), but was inversely associated with urinary tract cancer incidence (HR, 0.48; 95% CI, 0.23-1.00).

Conclusions: There was no increase in either overall or prostate cancer rates among men prenatally DES exposed relative to those unexposed. An unexpected risk reduction was observed for urinary system cancers among the exposed relative to those unexposed. These findings suggest that prenatal DES exposure is unlikely to be an important contributor to cancer development in middle-aged men.

Impact: The results of this study could lend reassurance to middle-aged men who were prenatally DES exposed that their exposure does not adversely influence their overall cancer risk.
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http://dx.doi.org/10.1158/1055-9965.EPI-21-0234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8492497PMC
October 2021

Deletion of in the mouse mammary gland results in abnormal accumulation of luminal progenitor cells: a link between reproductive factors and ER-/TNBC breast cancer?

Am J Cancer Res 2021 15;11(6):3263-3270. Epub 2021 Jun 15.

Department of Molecular and Cellular Biology, Roswell Park Comprehensive Cancer Center Buffalo, New York 14263, USA.

In humans, parity without breastfeeding increases risk of estrogen receptor-negative (ER-) breast cancer and is associated with hypermethylation of , a pioneer factor regulating lineage commitment of mammary gland luminal progenitor cells. We postulate that pregnancy-associated repression of results in the accumulation of aberrant, differentiation-arrested luminal progenitor cells which, following additional genetic and epigenetic insults, may give rise to ER- tumors. Consistent with this hypothesis, we show that deletion of in the mouse mammary gland results in a two-fold increase in the proportion of luminal progenitor cells and a reduction in mammary gland epithelial cells that stain positive for ER. These results provide compelling support for the notion that reduced expression is sufficient to alter mammary gland luminal cell fate determination , which could be a mechanism linking parity with ER- breast cancer.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263678PMC
June 2021

Cross-ancestry GWAS meta-analysis identifies six breast cancer loci in African and European ancestry women.

Nat Commun 2021 07 7;12(1):4198. Epub 2021 Jul 7.

Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.

Our study describes breast cancer risk loci using a cross-ancestry GWAS approach. We first identify variants that are associated with breast cancer at P < 0.05 from African ancestry GWAS meta-analysis (9241 cases and 10193 controls), then meta-analyze with European ancestry GWAS data (122977 cases and 105974 controls) from the Breast Cancer Association Consortium. The approach identifies four loci for overall breast cancer risk [1p13.3, 5q31.1, 15q24 (two independent signals), and 15q26.3] and two loci for estrogen receptor-negative disease (1q41 and 7q11.23) at genome-wide significance. Four of the index single nucleotide polymorphisms (SNPs) lie within introns of genes (KCNK2, C5orf56, SCAMP2, and SIN3A) and the other index SNPs are located close to GSTM4, AMPD2, CASTOR2, and RP11-168G16.2. Here we present risk loci with consistent direction of associations in African and European descendants. The study suggests that replication across multiple ancestry populations can help improve the understanding of breast cancer genetics and identify causal variants.
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http://dx.doi.org/10.1038/s41467-021-24327-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263739PMC
July 2021

Risk of Breast Cancer Among Carriers of Pathogenic Variants in Breast Cancer Predisposition Genes Varies by Polygenic Risk Score.

J Clin Oncol 2021 Aug 8;39(23):2564-2573. Epub 2021 Jun 8.

Population Health Sciences Department, Weill Cornell Medicine, New York, NY.

Purpose: This study assessed the joint association of pathogenic variants (PVs) in breast cancer (BC) predisposition genes and polygenic risk scores (PRS) with BC in the general population.

Methods: A total of 26,798 non-Hispanic white BC cases and 26,127 controls from predominately population-based studies in the Cancer Risk Estimates Related to Susceptibility consortium were evaluated for PVs in , , , , , , , , and . PRS based on 105 common variants were created using effect estimates from BC genome-wide association studies; the performance of an overall BC PRS and estrogen receptor-specific PRS were evaluated. The odds of BC based on the PVs and PRS were estimated using penalized logistic regression. The results were combined with age-specific incidence rates to estimate 5-year and lifetime absolute risks of BC across percentiles of PRS by PV status and first-degree family history of BC.

Results: The estimated lifetime risks of BC among general-population noncarriers, based on 10th and 90th percentiles of PRS, were 9.1%-23.9% and 6.7%-18.2% for women with or without first-degree relatives with BC, respectively. Taking PRS into account, more than 95% of , , and carriers had > 20% lifetime risks of BC, whereas, respectively, 52.5% and 69.7% of and carriers without first-degree relatives with BC, and 78.8% and 89.9% of those with a first-degree relative with BC had > 20% risk.

Conclusion: PRS facilitates personalization of BC risk among carriers of PVs in predisposition genes. Incorporating PRS into BC risk estimation may help identify > 30% of and nearly half of carriers below the 20% lifetime risk threshold, suggesting the addition of PRS may prevent overscreening and enable more personalized risk management approaches.
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http://dx.doi.org/10.1200/JCO.20.01992DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8330969PMC
August 2021

Abuse in Childhood and Risk for Sleep Disruption in Adulthood in the Black Women's Health Study.

Sleep Med 2021 07 10;83:260-270. Epub 2021 Mar 10.

Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA.

Objective: To investigate the association of early life abuse with sleep disruption risk in adulthood among U.S. Black women.

Methods: We analyzed data from the Black Women's Health Study, a prospective cohort study. In 2005, 29,998 women completed a self-administered questionnaire on early-life experiences of abuse (child and teen) and exposure to danger at any life stage. Participants reported on their sleep quality (snoring and diagnosed sleep apnea) in 2001, whether their "sleep was restless" in 2005, and their average sleep duration in 2009. We used log-binomial regression models to derive risk ratios (RRs) and 95% confidence intervals (CIs) for the association of child/teen abuse and danger at any life stage with snoring, diagnosis of sleep apnea, restless sleep, and short sleep duration.

Results: Nearly 50% of participants reported one or more measure of sleep disruption in adulthood. Higher severity of physical abuse was associated with increased risk of sleep disruption and higher severity of sexual abuse was associated with increased risk for most sleep disruptions. The RR comparing child/teen physical and sexual abuse relative to no abuse was highest for diagnosed sleep apnea (2.03, 95% CI: 1.70, 2.41). Feeling in danger at any life stage (child, teen, adult, past year) was generally associated with greater increases in risk of sleep disruption among women with a history of early life abuse than among women without such a history.

Conclusions: Our findings suggest that abuse as a child and/or teen is related to disrupted sleep in adulthood.
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http://dx.doi.org/10.1016/j.sleep.2021.02.053DOI Listing
July 2021

Comparison of the Prevalence of Pathogenic Variants in Cancer Susceptibility Genes in Black Women and Non-Hispanic White Women With Breast Cancer in the United States.

JAMA Oncol 2021 Jul;7(7):1045-1050

Slone Epidemiology Center at Boston University, Boston, Massachusetts.

Importance: The prevalence of germline pathogenic variants (PVs) in cancer susceptibility genes in US Black women compared with non-Hispanic White women with breast cancer is poorly described.

Objective: To determine whether US Black and non-Hispanic White women with breast cancer have a different prevalence of PVs in 12 cancer susceptibility genes.

Design, Setting, And Participants: Multicenter, population-based studies in the Cancer Risk Estimates Related to Susceptibility (CARRIERS) consortium. Participants were Black and non-Hispanic White women diagnosed with breast cancer, unselected for family history or age at diagnosis. Data were collected from June 1993 to June 2020; data analysis was performed between September 2020 and February 2021.

Main Outcomes And Measures: Prevalence of germline PVs in 12 established breast cancer susceptibility genes.

Results: Among 3946 Black women (mean [SD] age at diagnosis, 56.5 [12.02] y) and 25 287 non-Hispanic White women (mean [SD] age at diagnosis, 62.7 [11.14] y) with breast cancer, there was no statistically significant difference by race in the combined prevalence of PVs in the 12 breast cancer susceptibility genes evaluated (5.65% in Black vs 5.06% in non-Hispanic White women; P = .12). The prevalence of PVs in CHEK2 was higher in non-Hispanic White than Black patients (1.29% vs 0.38%; P < .001), whereas Black patients had a higher prevalence of PVs in BRCA2 (1.80% vs 1.24%; P = .005) and PALB2 (1.01% vs 0.40%; P < .001). For estrogen receptor-negative breast cancer, the prevalence of PVs was not different except for PALB2, which was higher in Black women. In women diagnosed before age 50 years, there was no difference in overall prevalence of PVs in Black vs non-Hispanic White women (8.83% vs 10.04%; P = .25), and among individual genes, only CHEK2 PV prevalence differed by race. After adjustment for age at diagnosis, the standardized prevalence ratio of PVs in non-Hispanic White relative to Black women was 1.08 (95% CI, 1.02-1.14), and there was no longer a statistically significant difference in BRCA2 PV prevalence.

Conclusions And Relevance: This large population-based case-control study revealed no clinically meaningful differences in the prevalence of PVs in 12 breast cancer susceptibility genes between Black and non-Hispanic White women with breast cancer. The findings suggest that there is not sufficient evidence to make policy changes related to genetic testing based on race alone. Instead, all efforts should be made to ensure equal access to and uptake of genetic testing to minimize disparities in care and outcomes.
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http://dx.doi.org/10.1001/jamaoncol.2021.1492DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160931PMC
July 2021

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

Carcinogenesis 2021 Jul;42(7):924-930

Slone Epidemiology Center at Boston University, Boston, MA, USA.

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.
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http://dx.doi.org/10.1093/carcin/bgab041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8496025PMC
July 2021

Religion and Spirituality among American Indian, South Asian, Black, Hispanic/Latina, and White Women in the Study on Stress, Spirituality, and Health.

J Sci Study Relig 2021 Mar 22;60(1):198-215. Epub 2020 Dec 22.

National Consortium on Psychosocial Stress, Spirituality, and Health, Boston, MA.

Social scientists have increasingly recognized the lack of diversity in survey research on American religion, resulting in a dearth of data on religion and spirituality (R/S) in understudied racial and ethnic groups. At the same time, epidemiological studies have increasingly diversified their racial and ethnic representation, but have collected few R/S measures to date. With a particular focus on American Indian and South Asian women (in addition to Blacks, Hispanic/Latinas, and white women), this study introduces a new effort among religion and epidemiology researchers, the Study on Stress, Spirituality, and Health (SSSH). This multi-cohort study provides some of the first estimates of R/S beliefs and practices among American Indians and U.S. South Asians, and offers new insight into salient beliefs and practices of diverse racial/ethnic and religious communities.
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http://dx.doi.org/10.1111/jssr.12695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127946PMC
March 2021

Dairy foods, calcium, and risk of breast cancer overall and for subtypes defined by estrogen receptor status: a pooled analysis of 21 cohort studies.

Am J Clin Nutr 2021 08;114(2):450-461

Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD, USA.

Background: Epidemiologic studies examining the relations between dairy product and calcium intakes and breast cancer have been inconclusive, especially for tumor subtypes.

Objective: To evaluate the associations between intakes of specific dairy products and calcium and risk of breast cancer overall and for subtypes defined by estrogen receptor (ER) status.

Method: We pooled the individual-level data of over 1 million women who were followed for a maximum of 8-20 years across studies. Associations were evaluated for dairy product and calcium intakes and risk of incident invasive breast cancer overall (n = 37,861 cases) and by subtypes defined by ER status. Study-specific multivariable hazard ratios (HRs) were estimated and then combined using random-effects models.

Results: Overall, no clear association was observed between the consumption of specific dairy foods, dietary (from foods only) calcium, and total (from foods and supplements) calcium, and risk of overall breast cancer. Although each dairy product showed a null or very weak inverse association with risk of overall breast cancer (P, test for trend >0.05 for all), differences by ER status were suggested for yogurt and cottage/ricotta cheese with associations observed for ER-negative tumors only (pooled HR = 0.90, 95% CI: 0.83, 0.98 comparing ≥60 g/d with <1 g/d of yogurt and 0.85, 95% CI: 0.76, 0.95 comparing ≥25 g/d with <1 g/d of cottage/ricotta cheese). Dietary calcium intake was only weakly associated with breast cancer risk (pooled HR = 0.98, 95% CI: 0.97, 0.99 per 350 mg/d).

Conclusion: Our study shows that adult dairy or calcium consumption is unlikely to associate with a higher risk of breast cancer and that higher yogurt and cottage/ricotta cheese intakes were inversely associated with the risk of ER-negative breast cancer, a less hormonally dependent subtype with poor prognosis. Future studies on fermented dairy products, earlier life exposures, ER-negative breast cancer, and different racial/ethnic populations may further elucidate the relation.
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http://dx.doi.org/10.1093/ajcn/nqab097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8326053PMC
August 2021

Evaluating Polygenic Risk Scores for Breast Cancer in Women of African Ancestry.

J Natl Cancer Inst 2021 Sep;113(9):1168-1176

Department of Oncology, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK.

Background: Polygenic risk scores (PRSs) have been demonstrated to identify women of European, Asian, and Latino ancestry at elevated risk of developing breast cancer (BC). We evaluated the performance of existing PRSs trained in European ancestry populations among women of African ancestry.

Methods: We assembled genotype data for women of African ancestry, including 9241 case subjects and 10 193 control subjects. We evaluated associations of 179- and 313-variant PRSs with overall and subtype-specific BC risk. PRS discriminatory accuracy was assessed using area under the receiver operating characteristic curve. We also evaluated a recalibrated PRS, replacing the index variant with variants in each region that better captured risk in women of African ancestry and estimated lifetime absolute risk of BC in African Americans by PRS category.

Results: For overall BC, the odds ratio per SD of the 313-variant PRS (PRS313) was 1.27 (95% confidence interval [CI] = 1.23 to 1.31), with an area under the receiver operating characteristic curve of 0.571 (95% CI = 0.562 to 0.579). Compared with women with average risk (40th-60th PRS percentile), women in the top decile of PRS313 had a 1.54-fold increased risk (95% CI = 1.38-fold to 1.72-fold). By age 85 years, the absolute risk of overall BC was 19.6% for African American women in the top 1% of PRS313 and 6.7% for those in the lowest 1%. The recalibrated PRS did not improve BC risk prediction.

Conclusion: The PRSs stratify BC risk in women of African ancestry, with attenuated performance compared with that reported in European, Asian, and Latina populations. Future work is needed to improve BC risk stratification for women of African ancestry.
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http://dx.doi.org/10.1093/jnci/djab050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8418423PMC
September 2021

Race, ethnicity and risk of second primary contralateral breast cancer in the United States.

Int J Cancer 2021 06 24;148(11):2748-2758. Epub 2021 Feb 24.

Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York, USA.

Breast cancer survivors have a high risk of a second primary contralateral breast cancer (CBC), but there are few studies of CBC risk in racial/ethnic minority populations. We examined whether the incidence and risk factors for CBC differed by race/ethnicity in the United States. Women with a first invasive Stage I-IIB breast cancer diagnosis at ages 20-74 years between 2000 and 2015 in the Surveillance, Epidemiology, and End Results Program (SEER) 18 registries were followed through 2016 for a diagnosis of invasive CBC ≥1 year after the first breast cancer diagnosis. We used cause-specific Cox proportional hazards models to test the association between race/ethnicity and CBC, adjusting for age, hormone receptor status, radiation therapy, chemotherapy and stage at first diagnosis, and evaluated the impact of contralateral prophylactic mastectomy, socioeconomic status, and insurance status on the association. After a median follow-up of 5.9 years, 9247 women (2.0%) were diagnosed with CBC. Relative to non-Hispanic (NH) White women, CBC risk was increased in NH Black women (hazard ratio = 1.44, 95% CI 1.35-1.54) and Hispanic women (1.11, 95% CI 1.02-1.20), with the largest differences among women diagnosed at younger ages. Adjustment for contralateral prophylactic mastectomy, socioeconomic status and health insurance did not explain the associations. Therefore, non-Hispanic Black and Hispanic women have an increased risk of CBC that is not explained by clinical or socioeconomic factors collected in SEER. Large studies of diverse breast cancer survivors with detailed data on treatment delivery and adherence are needed to inform interventions to reduce this disparity.
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http://dx.doi.org/10.1002/ijc.33501DOI Listing
June 2021

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

N Engl J Med 2021 02 20;384(5):440-451. Epub 2021 Jan 20.

From Mayo Clinic, Rochester, MN (C. Hu, S.N.H., R.G., K.Y.L., J.N., J.L., S. Yadav, N.J.B., T.L., J.E.O., C.S., C.M.V., E.C.P., F.J.C.); Harvard University T.H. Chan School of Public Health (H.H., C.G., D.J.H., P.K.), Slone Epidemiology Center at Boston University (K.A.B., J.R.P., L.R.), and Brigham and Women's Hospital (H.E.) - all in Boston; Qiagen, Hilden, Germany (R.S., J.K.); Roswell Park Comprehensive Cancer Center, Buffalo (C.B.A., S. Yao), and Weill Cornell Medicine, New York (R.T.) - both in New York; the University of California, Irvine (H.A.-C., A.Z.), Beckman Research Institute of City of Hope, Duarte (L.B., H.M., S.N., J.N.W.), Keck School of Medicine, University of Southern California, Los Angeles (C. Haiman), and Stanford University School of Medicine, Stanford (E.M.J., A.W.K.) - all in California; the University of Wisconsin-Milwaukee Joseph J. Zilber School of Public Health, Milwaukee (P.A.), and the University of Wisconsin-Madison, Madison (E.S.B., I.M.O., A.T.-D.); the Cancer Prevention and Control Program, Rutgers Cancer Institute of New Jersey, State University of New Jersey, New Brunswick (E.V.B.); the Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta (B.D.C., S.M.G., M.G., J.M.H., E.J.J., A.V.P.); the University of Oxford, Oxford, United Kingdom (D.J.H.); the Fred Hutchinson Cancer Research Center (C.K., P.A.N.) and the Department of Epidemiology, University of Washington (S.L.) - both in Seattle; the Epidemiology Program, University of Hawaii Cancer Center, Honolulu (L.L.M.); the National Institute of Environmental Health Sciences, Durham, NC (K.M.O., D.P.S., J.A.T., C.W.); Vanderbilt University, Nashville (T.P., S.R.); the University of Utah, Salt Lake City (D.E.G.); and the Department of Medicine and the Basser Center for BRCA, Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia (S.M.D., K.L.N.).

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 and 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 were associated with a moderate risk (odds ratio, 3.83; 95% CI, 2.68 to 5.63). Pathogenic variants in , , and were associated with increased risks of estrogen receptor-negative breast cancer and triple-negative breast cancer, whereas pathogenic variants in , , and 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 , 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.).
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http://dx.doi.org/10.1056/NEJMoa2005936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127622PMC
February 2021

Air pollution and breast cancer risk in the Black Women's Health Study.

Environ Res 2021 03 30;194:110651. Epub 2020 Dec 30.

Georgetown Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA.

Background: Air pollution contains numerous carcinogens and endocrine disruptors which may be relevant for breast cancer. Previous research has predominantly been conducted in White women; however, Black women may have higher air pollution exposure due to geographic and residential factors.

Objective: We evaluated the association between air pollution and breast cancer risk in a large prospective population of Black women.

Methods: We estimated annual average ambient levels of particulate matter <2.5 μm (PM), nitrogen dioxide (NO) and ozone (O) at the 1995 residence of 41,317 participants in the Black Women's Health Study who resided in 56 metropolitan areas across the United States. Cox proportional hazards regression was used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for an interquartile range (IQR) increase in each pollutant. We evaluated whether the association varied by menopausal status, estrogen receptor (ER) status of the tumor and geographic region of residence.

Results: With follow-up through 2015 (mean = 18.3 years), 2146 incident cases of breast cancer were confirmed. Higher exposure to NO or O was not associated with a higher risk of breast cancer. For PM, although we observed no association overall, there was evidence of modification by geographic region for both ER- (p for heterogeneity = 0.01) and premenopausal breast cancer (p for heterogeneity = 0.01). Among women living in the Midwest, an IQR increase in PM (2.87 μg/m), was associated with a higher risk of ER- (HR = 1.53, 95% CI: 1.07-2.19) and premenopausal breast cancer (HR = 1.32, 95% CI: 1.03-1.71). In contrast, among women living in the South, PM was inversely associated with both ER- (HR = 0.74, 95% CI: 0.56-0.97) and premenopausal breast cancer risk (HR = 0.75, 95% CI: 0.62-0.91).

Discussion: Overall, we observed no association between air pollution and increased breast cancer risk among Black women, except perhaps among women living in the Midwestern US.
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http://dx.doi.org/10.1016/j.envres.2020.110651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946730PMC
March 2021

Physical and sexual abuse in childhood and adolescence and leukocyte telomere length: A pooled analysis of the study on psychosocial stress, spirituality, and health.

PLoS One 2020 30;15(10):e0241363. Epub 2020 Oct 30.

MGH/Harvard Center on Genomics, Vulnerable Populations, and Health Disparities, Mongan Institute, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.

Introduction: We examined whether abuse in childhood and/or adolescence was associated with shorter telomere length in a pooled analysis of 3,232 participants from five diverse cohorts. We also assessed whether religion or spirituality (R/S) could buffer deleterious effects of abuse.

Methods: Physical and sexual abuse in childhood (age <12) and adolescence (age 12-18) was assessed using the Revised Conflict Tactics Scale and questions from a 1995 Gallup survey. We measured relative leukocyte telomere lengths (RTL) using quantitative real time polymerase chain reaction. We used generalized estimating equations to assess associations of physical and sexual abuse with log-transformed RTL z-scores. Analyses were conducted in each cohort, overall, and stratified by extent of religiosity or spirituality and religious coping in adulthood. We pooled study-specific estimates using random-effects models and assessed between-study heterogeneity.

Results: Compared to no abuse, severe sexual abuse was associated with lower RTL z-scores, in childhood: -15.6%, 95% CI: -25.9, -4.9; p-trend = 0.04; p-heterogeneity = 0.58 and in adolescence: -16.5%, 95% CI: -28.1, -3.0; p-trend = 0.08; p-heterogeneity = 0.68. Sexual abuse experienced in both childhood and adolescence was associated with 11.3% lower RTL z-scores after adjustment for childhood and demographic covariates (95% CI: -20.5%, -2.0%; p-trend = 0.03; p-heterogeneity = 0.62). There was no evidence of effect modification by R/S. Physical abuse was not associated with telomere length.

Conclusions: Sexual abuse in childhood or adolescence was associated with a marker of accelerated biological aging, decreased telomere length. The lack of moderation by R/S may be due to inability to capture the appropriate time period for those beliefs and practices.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0241363PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598522PMC
December 2020

Prenatal diethylstilbestrol exposure and risk of diabetes, gallbladder disease, and pancreatic disorders and malignancies.

J Dev Orig Health Dis 2021 08 28;12(4):619-626. Epub 2020 Oct 28.

Department of Health and Human Services, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Prenatal diethylstilbestrol (DES) exposure is associated with increased risk of hormonally mediated cancers and other medical conditions. We evaluated the association between DES and risk of pancreatic cancer and pancreatic disorders, type 2 diabetes, and gallbladder disease, which may be involved with this malignancy. Our analyses used follow-up data from the US National Cancer Institute DES Combined Cohort Study. Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for age, sex, cohort, body mass index, smoking, and alcohol for the association between prenatal DES exposure and type 2 diabetes, gallbladder disease (mainly cholelithiasis), pancreatic disorders (mainly pancreatitis), and pancreatic cancer among 5667 exposed and 3315 unexposed individuals followed from 1990 to 2017. Standardized incidence rate (SIR) ratios for pancreatic cancer were based on age-, race-, and calendar year-specific general population cancer incidence rates. In women and men combined, the hazards for total pancreatic disorders and pancreatitis were greater in the prenatally DES exposed than the unexposed (HR = 11, 95% CI 2.6-51 and HR = 7.0, 95% CI 1.5-33, respectively). DES was not associated overall with gallbladder disease (HR = 1.2, 95% CI 0.88-1.5) or diabetes (HR = 1.1, 95% CI 0.9-1.2). In women, but not in men, DES exposure was associated with increased risk of pancreatic cancer compared with the unexposed (HR: 4.1, 95% CI 0.84-20) or general population (SIR: 1.9, 95% CI 1.0-3.2). Prenatal DES exposure may increase the risk of pancreatic disorders, including pancreatitis in women and men. The data suggested elevated pancreatic cancer risk in DES-exposed women, but not in exposed men.
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http://dx.doi.org/10.1017/S2040174420000872DOI Listing
August 2021

Pregnancy outcomes and risk of endometrial cancer: A pooled analysis of individual participant data in the Epidemiology of Endometrial Cancer Consortium.

Int J Cancer 2021 05 17;148(9):2068-2078. Epub 2020 Nov 17.

Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy.

A full-term pregnancy is associated with reduced endometrial cancer risk; however, whether the effect of additional pregnancies is independent of age at last pregnancy is unknown. The associations between other pregnancy-related factors and endometrial cancer risk are less clear. We pooled individual participant data from 11 cohort and 19 case-control studies participating in the Epidemiology of Endometrial Cancer Consortium (E2C2) including 16 986 women with endometrial cancer and 39 538 control women. We used one- and two-stage meta-analytic approaches to estimate pooled odds ratios (ORs) for the association between exposures and endometrial cancer risk. Ever having a full-term pregnancy was associated with a 41% reduction in risk of endometrial cancer compared to never having a full-term pregnancy (OR = 0.59, 95% confidence interval [CI] 0.56-0.63). The risk reduction appeared the greatest for the first full-term pregnancy (OR = 0.78, 95% CI 0.72-0.84), with a further ~15% reduction per pregnancy up to eight pregnancies (OR = 0.20, 95% CI 0.14-0.28) that was independent of age at last full-term pregnancy. Incomplete pregnancy was also associated with decreased endometrial cancer risk (7%-9% reduction per pregnancy). Twin births appeared to have the same effect as singleton pregnancies. Our pooled analysis shows that, while the magnitude of the risk reduction is greater for a full-term pregnancy than an incomplete pregnancy, each additional pregnancy is associated with further reduction in endometrial cancer risk, independent of age at last full-term pregnancy. These results suggest that the very high progesterone level in the last trimester of pregnancy is not the sole explanation for the protective effect of pregnancy.
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http://dx.doi.org/10.1002/ijc.33360DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969437PMC
May 2021

Epidemiology of Basal-like and Luminal Breast Cancers among Black Women in the AMBER Consortium.

Cancer Epidemiol Biomarkers Prev 2021 01 23;30(1):71-79. Epub 2020 Oct 23.

Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.

Background: Evidence suggests etiologic heterogeneity among breast cancer subtypes. Previous studies with six-marker IHC classification of intrinsic subtypes included small numbers of black women.

Methods: Using centralized laboratory results for estrogen receptor (ER), progesterone receptor, HER2, proliferation marker, Ki-67, EGFR, and cytokeratin (CK)5/6, we estimated case-only and case-control ORs for established breast cancer risk factors among cases ( = 2,354) and controls ( = 2,932) in the African American Breast Cancer Epidemiology and Risk (AMBER) consortium. ORs were estimated by ER status and intrinsic subtype using adjusted logistic regression.

Results: Case-only analyses by ER status showed etiologic heterogeneity by age at menarche, parity (vs. nulliparity), and age at first birth. In case-control analyses for intrinsic subtype, increased body mass index and waist-to-hip ratio (WHR) were associated with increased risk of luminal A subtype, whereas older age at menarche and parity, regardless of breastfeeding, were associated with reduced risk. For basal-like cancers, parity without breastfeeding and increasing WHR were associated with increased risk, whereas breastfeeding and age ≥25 years at first birth were associated with reduced risk among parous women. Basal-like and ER/HER2 subtypes had earlier age-at-incidence distribution relative to luminal subtypes.

Conclusions: Breast cancer subtypes showed distinct etiologic profiles in the AMBER consortium, a study of more than 5,000 black women with centrally assessed tumor biospecimens.

Impact: Among black women, high WHR and parity without breastfeeding are emerging as important intervention points to reduce the incidence of basal-like breast cancer.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-0556DOI Listing
January 2021

High Consumption of Red Meat Is Associated with Excess Mortality Among African-American Women.

J Nutr 2020 12;150(12):3249-3258

Slone Epidemiology Center, Boston University School of Medicine , Boston, MA, USA.

Background: Red meat is a rich source of nutrients but is typically high in saturated fats. Carcinogenic chemicals can be formed during cooking and processing. Little is known about the relation of red meat consumption to mortality in African Americans (AAs), a group with excess mortality and high consumption of red meat relative to whites.

Objective: Our objective was to assess the association between red meat consumption and mortality in AA women.

Methods: The Black Women's Health Study (BWHS) is a prospective cohort study of AA women across the USA who completed health questionnaires at enrollment in 1995 (median age 38 y, median BMI 27.9 kg/m2) and every 2 y thereafter. The analyses included 56,314 women who completed a validated FFQ and were free of cardiovascular disease and cancer at baseline in 1995. Exposures were total red meat, processed red meat, and unprocessed red meat consumption. Outcomes were all-cause and cause-specific mortality. Cox proportional hazards models with control for age, socioeconomic status, lifestyle factors, medical history, and dietary factors were used to estimate HRs with 95% CIs.

Results: During 22 y of follow-up through to 2017, we identified 5054 deaths, which included 1354 cardiovascular deaths and 1801 cancer deaths. The HR for all-cause mortality was 1.47 (95% CI: 1.33, 1.62) for the highest quintile of total red meat consumption relative to the lowest. Each 1 serving/d increase in red meat consumption was associated with a 7% (95% CI: 5%, 9%) increased risk of all-cause mortality. Red meat consumption was also associated with increased cardiovascular mortality, but not with cancer mortality. Results were similar for the consumption of processed and unprocessed red meat.

Conclusions: Red meat consumption is associated with increased all-cause and cardiovascular mortality among AA women.
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http://dx.doi.org/10.1093/jn/nxaa282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726124PMC
December 2020

Genetic variants in anti-Müllerian hormone-related genes and breast cancer risk: results from the AMBER consortium.

Breast Cancer Res Treat 2021 Jan 22;185(2):469-478. Epub 2020 Sep 22.

Department of Epidemiology, University of North Carolina Gillings School of Global Public Health, 2104F McGavran-Greenberg Hall, Chapel Hill, NC, 27599-7435, USA.

Purpose: Circulating anti-Müllerian hormone (AMH) levels are positively associated with time to menopause and breast cancer risk. We examined breast cancer associations with single nucleotide polymorphisms (SNPs) in the AMH gene or its receptor genes, ACVR1 and AMHR2, among African American women.

Methods: In the AMBER consortium, we tested 65 candidate SNPs, and 1130 total variants, in or near AMH, ACVR1, and AMHR2 and breast cancer risk. Overall, 3649 cases and 4230 controls contributed to analyses. Odds ratios (OR) and 95% confidence intervals (CI) for breast cancer were calculated using multivariable logistic regression.

Results: After correction for multiple comparisons (false-discovery rate of 5%), there were no statistically significant associations with breast cancer risk. Without correction for multiple testing, four candidate SNPs in ACVR1 and one near AMH were associated with breast cancer risk. In ACVR1, rs13395576[C] was associated with lower breast cancer risk overall (OR 0.84; 95% CI 0.72, 0.97) and for ER+ disease (OR 0.75; CI 0.62, 0.89) (p < 0.05). Rs1220110[A] and rs1220134[T] each had ORs of 0.89-0.90 for postmenopausal and ER+ breast cancer (p ≤ 0.03). Conversely, rs1682130[T] was associated with higher risk of ER+ breast cancer (OR 1.17; 95% CI 1.04, 1.32). Near AMH, rs6510652[T] had ORs of 0.85-0.90 for breast cancer overall and after menopause (p ≤ 0.02).

Conclusions: The present results, from a large study of African American women, provide limited support for an association between AMH-related polymorphisms and breast cancer risk and require replication in other studies.
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http://dx.doi.org/10.1007/s10549-020-05944-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867570PMC
January 2021
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