To investigate uterine leiomyomata (UL) incidence in relation to polymorphisms in genes involved in vitamin D metabolism and skin pigmentation. Rates of UL are 2-3 times higher in African Americans ...than in European Americans. Recent studies suggest that vitamin D deficiency is associated with an increased risk of UL.
Nested case-control study.
Not applicable.
Two thousand two hundred thirty-two premenopausal women first diagnosed with UL confirmed by ultrasound or surgery during 1997-2011 (cases) and 2,432 premenopausal women never diagnosed with UL through 2011 (controls).
None.
Self-reported UL. We used logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association between each polymorphism and UL, controlling for age, geographic region, and ancestry.
Three of 12 polymorphisms were associated with UL at the nominal significance level: rs4944957 and rs12800438 near DHCR7 and rs6058017 in ASIP. After correction for multiple hypothesis testing, two single nucleotide polymorphisms remained significantly associated with UL (rs12800438 and rs6058017). Compared with the AA genotype for rs12800438 (correlated with higher serum 25OHD levels), ORs were 1.09 (95% CI, 0.92, 1.29) and 1.23 (95% CI, 1.03, 1.47) for the GA and GG genotypes, respectively. Compared with the AA genotype for rs6058017 (correlated with lighter skin pigmentation), ORs were 1.01 (95% CI, 0.83, 1.22) and 1.18 (95% CI, 0.97, 1.44) for the GA and GG genotypes, respectively.
Our data support the hypothesis that vitamin D deficiency is involved in UL etiology.
Abstract Objectives Early age at natural menopause has been associated with increased all-cause mortality in several studies, although the literature is not consistent. This relation has not been ...examined among African American women. Study design Data were from the Black Women's Health Study, a follow-up study of African-American women enrolled in 1995. Among 11,212 women who were naturally menopausal at entry to the study or during follow-up through 2008, we assessed the relation of age at natural menopause to all-cause and cause-specific mortality. At baseline and biennially, participants reported on reproductive and medical history, including gynecologic surgeries and exogenous hormone use. Mortality data were obtained from the National Death Index. Multivariable Cox proportional hazard models were used to estimate mortality rate ratios (MRR) and 95% confidence intervals (CI) for categories of age at menopause. Results Of 692 deaths identified during 91,829 person years of follow-up, 261 were due to cancer, 199 to cardiovascular diseases and 232 to other causes. Natural menopause before age 40 was associated with increased all-cause mortality (MRR = 1.34, 95% CI 0.96–1.84, relative to menopause at 50–54 years; P -trend = 0.04) and with the subcategories of death considered – cancer, cardiovascular disease, and all other causes. The associations were present among never and ever users of postmenopausal female hormones and among never and ever smokers. Conclusions In this large prospective cohort of African-American women, natural menopause before age 40 was associated with a higher rate of all-cause and cause-specific mortality. These findings provide support for the theory that natural menopause before age 40 may be a marker of accelerated somatic aging.
Purpose
The objective of this study was to evaluate whether time spent sitting at work or watching television was associated with breast cancer risk among African American women.
Methods
The Black ...Women’s Health Study (analytic cohort = 46,734) is an ongoing prospective cohort study of African American women ages 21–69 at baseline (1995). Questionnaire data were used to estimate sedentary time. Total time spent sitting at work and watching television (individually and combined) at baseline and updated through follow-up (1995–2001) and breast cancer incidence (
n
= 2,041 incident cases, 1995–2013) was evaluated using proportional hazards regression.
Results
Higher total time spent sitting at baseline (≥10 vs. <5 h/day, HR 1.27, 95 % CI 1.06, 1.53) and updated through follow-up (≥10 vs. <5 h/day, HR 1.38, 95 % CI 1.14, 1.66) was associated with an increased breast cancer risk. Associations were stronger for hormone receptor-negative tumors (≥10 vs. <5 h/day, HR 1.70, 95 % CI 1.12, 2.55) compared to hormone receptor-positive tumors (≥10 vs. <5 h/day, HR 1.16, 95 % CI 0.88, 1.52), but tests for heterogeneity were not statistically significant (
p
heterogeneity = 0.31). Positive associations between total time spent sitting and breast cancer incidence did not differ by physical activity level or body composition measurements.
Conclusions
Our findings suggest that high sedentary time may increase risk for breast cancer among African American women.
The relation of body mass index (BMI) and weight gain to breast cancer risk is complex, and little information is available on Black women, among whom the prevalence of obesity is high. We assessed ...BMI and weight gain in relation to breast cancer risk in prospective data from the Black Women's Health Study. In 1995, 59,000 African American women enrolled in the Black Women's Health Study by completing mailed questionnaires. Data on anthropometric factors were obtained at baseline and every 2 years afterwards. In 10 years of follow-up, 1,062 incident cases of breast cancer occurred. Incidence rate ratios (IRR) were computed in multivariable Cox proportional hazards regression. BMI at age 18 years of >/=25 relative to <20 was associated with a reduced risk of breast cancer among both premenopausal women (IRR, 0.68; 95% confidence interval, 0.46-0.98) and postmenopausal women (IRR, 0.53; 95% confidence interval, 0.35-0.81). There was an inverse association of current BMI with premenopausal breast cancer but no association with postmenopausal breast cancer, either overall or among never-users of hormone therapy. Weight gain was not associated with postmenopausal breast cancer risk. In analyses restricted to breast cancers that were estrogen and progesterone receptor positive, IRRs for current BMI and weight gain were elevated but not statistically significant. The findings indicate that being overweight at age 18 years is associated with a reduced risk of both premenopausal and postmenopausal breast cancer in African American women. Understanding the reasons for the association may help elucidate the pathways through which adolescent exposures influence breast cancer risk. The lack of association of obesity with receptor-negative tumors in postmenopausal African American women may partially explain why breast cancer incidence in older Black women is not high relative to other ethnic groups in spite of the high prevalence of obesity in Black women.
Physical activity has been associated with reduced risk of breast cancer. Evidence on the association in African Americans is limited.
With prospective data from the Black Women's Health Study, we ...assessed vigorous exercise and walking in relation to incidence of invasive breast cancer overall (n = 1,364), estrogen receptor-positive (ER(+), n = 688) cancer, and estrogen receptor-negative (ER(-), n = 405) cancer, based on 307,672 person-years of follow-up of 44,708 African-American women ages 30 years or older at enrollment. Cox proportional hazards models estimated incidence rate ratios (IRR) and 95% confidence intervals (CI).
Vigorous exercise at baseline was inversely associated with overall breast cancer incidence (Ptrend = 0.05): the IRR for ≥7 h/wk relative to <1 h/wk was 0.74 (95% CI, 0.57-0.96). The association did not differ by ER status. Brisk walking for ≥7 h/wk was associated with a reduction similar to that for vigorous exercise. Vigorous exercise at the age of 30 years, 21 years, or in high school was not associated with breast cancer incidence. Sitting for long periods at work or watching TV was not significantly associated with breast cancer incidence.
High levels of vigorous exercise or brisk walking may be associated with a reduction in incidence of breast cancer in African-American women.
These results provide informative data on a potential modifiable risk factor, exercise, for breast cancer in African-American women.
Constitutional immunity shaped by exposure to endemic infectious diseases and parasitic worms in Sub-Saharan Africa may play a role in the etiology of breast cancer among African American (AA) women.
...A total of 149,514 gene variants in 433 genes across 45 immune pathways were analyzed in the AMBER consortium among 3,663 breast cancer cases and 4,687 controls. Gene-based pathway analyses were conducted using the adaptive rank truncated product statistic for overall breast cancer risk, and risk by estrogen receptor (ER) status. Unconditional logistic regression analysis was used to estimate ORs and 95% confidence intervals (CIs) for single variants.
The top pathways were Interleukin binding (
= 0.01), Biocarta TNFR2 (
= 0.005), and positive regulation of cytokine production (
= 0.024) for overall, ER
, and ER
cancers, respectively. The most significant gene was
(
= 0.001) for overall cancer, with rs228952 being the top variant identified (OR = 0.85; 95% CI, 0.79-0.92). Only
contained a significant variant for ER
breast cancer. Variants in
, and
were associated with ER
disease. The only genes showing heterogeneity between ER
and ER
cancers were
, and
(
≤ 0.02). We also noted genes associated with autoimmune and atopic disorders.
Findings from this study suggest that genetic variants in immune pathways are relevant to breast cancer susceptibility among AA women, both for ER
and ER
breast cancers.
Results from this study extend our understanding of how inherited genetic variation in immune pathways is relevant to breast cancer susceptibility.
.
Depressive symptoms and risk of uterine leiomyomata Wise, Lauren A., ScD; Li, Se, PhD; Palmer, Julie R., ScD ...
American journal of obstetrics and gynecology,
05/2015, Letnik:
212, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Objective Uterine leiomyomata (UL) are a major source of gynecologic morbidity and the primary indication for hysterectomy. Depression can cause dysregulation of the hypothalamic-pituitary-adrenal ...axis, which may affect the synthesis of reproductive hormones involved in UL pathogenesis. We assessed the association between depressive symptoms and UL among 15,963 premenopausal women. Study Design Data were derived from the Black Women’s Health Study, a prospective cohort study. In 1999 and 2005, the Center for Epidemiologic Studies Depression Scale (CES-D) was used to ascertain depressive symptoms. On biennial follow-up questionnaires from 1999 through 2011, women reported physician-diagnosed depression, antidepressant use, and UL diagnoses. Incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox regression. Results There were 4722 incident UL cases diagnosed by ultrasound (n = 3793) or surgery (n = 929) during 131,262 person-years of follow-up. Relative to baseline CES-D scores <16, IRRs were 1.05 (95% CI, 0.98–1.13) for CES-D scores 16-24 and 1.16 (95% CI, 1.06–1.27) for CES-D scores ≥25 ( P -trend = .001). IRRs for current and past physician-diagnosed depression relative to no depression were 1.15 (95% CI, 0.98–1.34) and 1.25 (95% CI, 1.13–1.39), respectively. Results persisted after further control for antidepressant use. IRRs for current and past use of antidepressants (any indication) relative to never use were 1.11 (95% CI, 0.97–1.28) and 1.32 (95% CI, 1.14–1.52), respectively. Conclusion In this cohort of black women, greater depressive symptoms were associated with UL, independent of antidepressant use, supporting the hypothesis that dysregulation of the hypothalamic-pituitary-adrenal axis increases UL risk.
African American women are disproportionately affected by type 2 diabetes. Genetic factors may explain part of the excess risk. More than 100 genetic variants have been associated with risk of type 2 ...diabetes, but most studies have been conducted in white populations. Two genome-wide association studies (GWAS) in African Americans have identified three novel genetic variants only. We conducted admixture mapping using 2918 ancestral informative markers in 2632 cases of type 2 diabetes, and 2596 controls nested in the ongoing Black Women's Health Study cohort, with the goal of identifying genomic loci with local African ancestry associated with type 2 diabetes. In addition, we performed replication analysis of 71 previously identified index SNPs, and fine-mapped those genetic loci to identify better or new genetic variants associated with type 2 diabetes in African Americans. We found that individual African ancestry was associated with higher risk of type 2 diabetes. In addition, we identified two genomic regions, 3q26 and 12q23, with excess of African ancestry associated with higher risk of type 2 diabetes. Lastly, we replicated 8 out of 71 index SNPs from previous GWAS, including, for the first time in African Americans, the X-linked rs5945326 SNP near the DUSP9 gene. In addition, our fine-mapping efforts suggest independent signals at five loci. Our detailed analysis identified two genomic regions associated with risk of type 2 diabetes, and showed that many genetic risk variants are shared across ancestries.
Compared to U.S. white women, African American women are more likely to die from ductal carcinoma in situ (DCIS). Elucidation of risk factors for DCIS in African American women may provide ...opportunities for risk reduction.
We used data from three epidemiologic studies in the African American Breast Cancer Epidemiology and Risk Consortium to study risk factors for estrogen receptor (ER) positive DCIS (488 cases; 13,830 controls). Results were compared to associations observed for ER+ invasive breast cancer (n = 2,099).
First degree family history of breast cancer was associated with increased risk of ER+ DCIS odds ratio (OR): 1.69, 95% confidence interval (CI): 1.31, 2.17. Oral contraceptive use within the past 10 years (vs. never) was also associated with increased risk (OR: 1.43, 95%CI: 1.03, 1.97), as was late age at first birth (≥25 years vs. <20 years) (OR: 1.26, 95%CI: 0.96, 1.67). Risk was reduced in women with older age at menarche (≥15 years vs. <11 years) (OR: 0.62, 95%CI: 0.42, 0.93) and higher body mass index (BMI) in early adulthood (≥25 vs. <20 kg/m2 at age 18 or 21) (OR: 0.75, 95%CI: 0.55, 1.01). There was a positive association of recent BMI with risk in postmenopausal women only. In general, associations of risk factors for ER+ DCIS were similar in magnitude and direction to those for invasive ER+ breast cancer.
Our findings suggest that most risk factors for invasive ER+ breast cancer are also associated with increased risk of ER+ DCIS among African American women.
•Few studies of risk factors for ductal carcinoma in situ (DCIS) have evaluated associations for African American women.•We analyzed data from the African American African American Breast Cancer Epidemiology and Risk (AMBER) Consortium.•Family history of breast cancer, reproductive factors, and anthropometric factors were associated with risk of ER+ DCIS.•In general, risk factor associations for ER+ DCIS were similar to those for ER+ invasive breast cancer.•Our findings support a common etiology and pathogenesis between ER+ DICS and ER+ invasive cancer in African American women.
Hair loss on the central scalp commonly occurs among African American (AA) women and can pose substantial psychosocial burdens. The causes of hair loss remain obscure, although type 2 diabetes has ...been hypothesized to increase the risk of hair loss. The objective of the present study was to prospectively estimate the association between type 2 diabetes and severe central hair loss in AA women.
The Black Women’s Health Study has collected data on medical and lifestyle factors, including diagnosis of type 2 diabetes, biennially since 1995 from AA women across the United States. The present analysis was based on responses from 5389 women to an online hair loss questionnaire in 2015. Respondents indicated severity of central hair loss on a validated six-item photographic scale; the highest levels, levels 3 to 5, were designated as severe. We used Cox proportional hazards models to estimate multivariable hazard ratios and 95% confidence intervals (CIs) for type 2 diabetes in relation to severe central hair loss.
During the follow-up period, 850 cases of severe hair loss occurred. The multivariable hazard ratio for severe hair loss associated with diabetes was 1.68 (95% CI, 1.38-2.06) overall, and 2.05 (95% CI, 1.48-2.85) for diabetes duration of ≥10 years.
Type 2 diabetes was associated with an increased risk of severe central scalp hair loss in AA women. Patients with type 2 diabetes should be followed closely for central scalp hair loss so that appropriate treatment can be offered.
PDF
