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1.
Int J Cancer ; 2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33433939

RESUMO

When powder is applied to the genital area, it has the potential to reach internal reproductive organs and promote carcinogenesis by irritating and inflaming exposed tissues. Although many studies have considered the association between genital powder use and ovarian cancer risk, the relationship between genital powder use and uterine cancer is less well-studied. We pooled data from four large, prospective cohorts (the Nurses' Health Study, the Nurses' Health Study II, the Sister Study and the Women's Health Initiative - Observational Study). We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for prespecified confounders. In total, 209 185 women were included, with 37% reporting ever genital powder use. Over a mean 14.5 years of follow-up, 3272 invasive uterine cancers were diagnosed. There was no overall association between ever genital powder use and uterine cancer (HR = 1.01, 95% CI: 0.94-1.09), with little difference observed for frequent (≥1 times/week) vs never use (HR = 1.05, 95% CI: 0.95-1.16; P-for-trend = .46). Long-term use (>20 years; HR = 1.12, 95% CI: 0.96-1.31; P-for-trend = 0.14) was associated with a small, but not statistically significant, increase in risk, compared to never use. There were not clear differences by uterine cancer histologic subtypes or across strata of relevant covariates, including race/ethnicity, follow-up time, menopausal status and body mass index. The results of this large, pooled analysis do not support a relationship between the use of genital powder and uterine cancer, although the positive associations observed for long-term use may merit further consideration.

2.
N Engl J Med ; 384(5): 440-451, 2021 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-33471974

RESUMO

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.).


Assuntos
Neoplasias da Mama/genética , Predisposição Genética para Doença/genética , Variação Genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade , Mutação , Razão de Chances , Risco , Análise de Sequência de DNA , Adulto Jovem
3.
Artigo em Inglês | MEDLINE | ID: mdl-33293341

RESUMO

BACKGROUND: Iron is both essential to life and potentially toxic at higher levels. Epidemiologic studies of iron and breast cancer are sparse, with substantial heterogeneity found in a recent meta-analysis. Evidence based on a comprehensive set of iron biomarkers and a large sample size could help clarify relationships between iron body stores and breast cancer risk. METHODS: A case-cohort sample of 6,008 women, including 3,011 incident cases, has been followed for a median of 7.9 years. We estimated breast cancer hazard ratios (HRs) with Cox models including age as the primary time scale and including in turn iron, ferritin, percent transferrin saturation, and their first principal component both as categorical (quartiles) and continuous measures. RESULTS: Adjusted HRs for the highest versus lowest quartiles of iron, ferritin, and transferrin saturation (95% CI) were 1.06 (0.90, 1.25), 1.03 (0.87, 1.23), and 0.94 (0.80, 1.12), respectively, and 1.06 (0.90, 1.25) for the first principal component. Associations were similar when follow-up time was restricted to ≤4 years or >2 years. Post-hoc analyses suggested low iron stores are associated with reduced breast cancer risk, in both pre- and postmenopause and the obese. CONCLUSIONS: A study with one of the largest sample sizes to date and with all three measures of circulating iron, ferritin, and transferrin saturation does not support a strong association between elevated iron stores and breast cancer risk. Further investigation of low iron may be warranted. IMPACT: These results do not support a strong association between iron overload and breast cancer incidence.

4.
JAMA Netw Open ; 3(11): e2024329, 2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33146735

RESUMO

Importance: Neighborhood deprivation is associated with age-related disease, mortality, and reduced life expectancy. However, biological pathways underlying these associations are not well understood. Objective: To evaluate the association between neighborhood deprivation and epigenetic measures of age acceleration and genome-wide methylation. Design, Setting, and Participants: This cross-sectional study used data from the Sister Study, a prospective cohort study comprising 50 884 women living in the US and Puerto Rico aged 35 to 74 years at enrollment who had a sister with breast cancer but had not had breast cancer themselves. Cohort enrollment occurred between July 2003 and March 2009. Participants completed a computer-assisted telephone interview on demographic, socioeconomic, lifestyle, and residential factors and provided anthropometric measures and peripheral blood samples at a home examination. DNA methylation data obtained for 2630 non-Hispanic White women selected for a case-cohort study in 2014 were used in this cross-sectional analysis. DNA methylation was measured using the HumanMethylation450 BeadChips in whole blood samples collected at baseline. Data analysis for this study was performed from October 17, 2019, to August 27, 2020. Exposures: Each participants' primary address was linked to an established index of neighborhood deprivation. Main Outcomes and Measures: Epigenetic age was estimated using 4 epigenetic clocks (Horvath, Hannum, PhenoAge, and GrimAge). Age acceleration was determined using residuals from regressing chronologic age on each of the 4 epigenetic age metrics. Linear regression was used to estimate associations between neighborhood deprivation and epigenetic age acceleration as well as DNA methylation at individual cytosine-guanine sites across the genome. Results: Mean (SD) age of the 2630 participants was 56.9 (8.7) years. Those with the greatest (>75th percentile) vs least (≤25th percentile) neighborhood deprivation had higher epigenetic age acceleration estimated by Hannum (ß = 0.23; 95% CI, 0.01-0.45), PhenoAge (ß = 0.28; 95% CI, 0.06-.50), and GrimAge (ß = 0.37; 95% CI, 0.12-0.62). Increasing US quartiles of neighborhood deprivation exhibited a trend with Hannum, PhenoAge, and GrimAge. For example, GrimAge showed a significant dose-response (P test for trend <.001) as follows: level 2 vs level 1 (ß = 0.30; 95% CI, 0.17-0.42), level 3 vs level 1 (ß = 0.35; 95% CI, 0.19-0.50), and level 4 vs level 1 (ß = 0.37; 95% CI, 0.12-0.62). Neighborhood deprivation was found to be associated with 3 cytosine-phosphate-guanine sites, with 1 of these annotated to a known gene MAOB (P = 9.71 × 10-08). Conclusions and Relevance: The findings of this study suggest that residing in a neighborhood with a higher deprivation index appears to be reflected by methylation-based markers of aging.

5.
Int J Epidemiol ; 2020 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-33247915

RESUMO

BACKGROUND: Familial clustering of age at onset would have implications for both personalized screening and aetiology, but has not been studied for breast cancer. METHODS: We prospectively studied a cohort of 23 145 sisters to explore whether their breast cancer risk changed near the age at diagnosis of a previously affected older sister. Using an age-time-dependent variable in a Cox regression model, we estimated hazard ratios for breast cancer when participants were near their sister's diagnosis age, relative to similarly aged women whose sister was diagnosed at a very different age. To rule out a correlation driven by young-onset familial cancer, we separately investigated women who had enrolled at age 50 or older. RESULTS: Of the 23 145 women, 1412 developed breast cancer during follow-up (median 9.5 years). The estimated hazard ratio was 1.80 (95% confidence interval: 1.18, 2.74) at their sister's age at diagnosis, suggesting a substantial increase in risk compared with women of the same age but whose sister was diagnosed at a very different age. Restriction to women who enrolled at or after age 50 produced similar results. CONCLUSIONS: This familial clustering suggests that there may be important genetic and/or early environmental risk factors that influence the timing of breast cancer, even when onset is late in life. Personalized screening might need to account for the age at which a sister was earlier diagnosed with breast cancer.

6.
Int J Cancer ; 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-33252833

RESUMO

Hair products can contain hormonally active and carcinogenic compounds. Adolescence may be a period of enhanced susceptibility of the breast tissue to exposure to chemicals. We therefore evaluated associations between adolescent hair product use and breast cancer risk. Sister Study participants (ages 35-74 years) who had completed enrollment questionnaires (2003-2009) on use of hair dyes, straighteners/relaxers, and perms at ages 10-13 years (N = 47 522) were included. Cox proportional hazards regression was used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs) for associations between hair products and incident breast cancer (invasive cancer or ductal carcinoma in situ), with consideration of heterogeneity by menopausal status and race/ethnicity. Over an average of 10 years of follow-up, 3380 cases were diagnosed. Frequent use of straighteners and perms was associated with a higher risk of premenopausal (HR = 2.11, 95% CI 1.26-3.55 and HR = 1.55, 95%CI: 0.96-2.53, respectively) but not postmenopausal breast cancer (HR = 0.99, 95% CI: 0.76-1.30 and HR = 1.09, 95% CI: 0.89-1.35, respectively). Permanent hair dye use during adolescence was uncommon (<3%) and not associated with breast cancer overall (HR = 0.97, 95% CI: 0.78-1.20), though any permanent dye use was associated with a higher risk among Black women (HR = 1.77, 95% CI: 1.01-3.11). Although frequency of use of perms (37% non-Hispanic white vs 9% Black) and straighteners (3% non-Hispanic white vs 75% Black) varied by race/ethnicity, associations with breast cancer did not. Use of hair products, specifically perms and straighteners, during adolescence may be associated with a higher risk of premenopausal breast cancer. This article is protected by copyright. All rights reserved.

7.
Cancer ; 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33237602

RESUMO

BACKGROUND: Data from a nationwide sample of US breast cancer survivors were used to examine associations between patient characteristics (breast cancer clinical features, prognostic factors, and treatments) and health-related quality of life (HRQOL). Associations between postdiagnosis HRQOL and mortality were then evaluated. METHODS: The authors identified female breast cancer survivors (n = 2453) from the Sister Study or Two Sister Study who were at least 1 year from breast cancer diagnosis and who had responded to a survivorship survey in 2012. HRQOL was assessed with the Patient-Reported Outcomes Measurement Information System (PROMIS) Global 10 measures. Multivariable linear regression was used to assess predictors associated with HRQOL. Cox regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between HRQOL and all-cause mortality. RESULTS: HRQOL, assessed an average of 4.9 years after the cancer diagnosis (standard deviation of 1.9 years), was negatively associated with a higher cancer stage at diagnosis; a higher comorbidity score at the survey; experience of surgical complications; dissatisfaction with breast surgery; and experience of any recent recurrence, metastasis, or secondary malignancy. Since the completion of the survey, there were 85 deaths (3.5%) during a mean follow-up of 4 years (standard deviation of 0.5 years). In multivariate models, decreases in PROMIS physical T scores and mental T scores were associated with increased mortality (HR for physical T scores, 1.08; 95% CI, 1.05-1.11; HR for mental T scores, 1.03; 95% CI, 1.01-1.06). CONCLUSIONS: Prognostic and cancer treatment-related factors affect HRQOL in breast cancer survivors and may inform targeted survivorship care. PROMIS global health measures may offer additional insights into patients' well-being and mortality risk. LAY SUMMARY: Findings from a study suggest that prognostic and cancer treatment-related factors affect health-related quality of life (HRQOL) in breast cancer survivors and that poor HRQOL may increase the mortality risk. The evaluation of HRQOL is important because it may hold potential as a tool for optimizing survivorship care.

8.
Breast Cancer Res ; 22(1): 112, 2020 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-33109223

RESUMO

BACKGROUND: Earlier age at menarche is an established risk factor for breast cancer. While age at menarche has been fairly stable over the past half-century, age at breast development (thelarche) has continued to decrease. Recently, earlier age at thelarche and a longer time between thelarche and menarche (pubertal tempo) were shown to be associated with increased breast cancer risk. Our objective was to examine how breast cancer risk was associated with pubertal timing and tempo in a prospective US cohort. METHODS: Women ages 35-74 years without a history of breast cancer, but who had a sister previously diagnosed with breast cancer, were enrolled in the Sister Study from 2003 to 2009 (N = 50,884). At enrollment, participants reported their ages at thelarche and menarche. Pubertal tempo was age at menarche minus age at thelarche. We estimated adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for each pubertal milestone and risk of breast cancer (invasive or ductal carcinoma in situ) using Cox proportional hazards regression. We examined whether associations between age at thelarche and breast cancer risk were modified by birth cohort, race/ethnicity, weight at age 10, and extent of breast cancer family history, as characterized by a Bayesian score based on first-degree family structure. RESULTS: During follow-up (mean = 9.3 years), 3295 eligible women were diagnosed with breast cancer. Early ages at thelarche (HR = 1.23, 95% CI 1.03-1.46 for < 10 vs. 12-13 years) and menarche (HR = 1.10, 95% CI 1.01-1.20 for < 12 vs. 12-13 years) were positively associated with breast cancer risk. Pubertal tempo was not associated with breast cancer risk (HR = 0.99, 95% CI 0.97-1.02 per 1-year longer tempo). When considering early thelarche (< 10 years) and early menarche (< 12 years) jointly, women with both had a 30% greater risk of breast cancer compared with women with neither risk factor (95% CI 1.07-1.57). The association between age at thelarche and breast cancer risk did not significantly vary by birth cohort, race/ethnicity, childhood weight, or Bayesian family history score. CONCLUSIONS: Earlier ages at thelarche and menarche may enhance susceptibility to breast carcinogenesis. Age at thelarche is an important risk factor to consider given secular trends towards earlier development.

9.
Environ Res ; 191: 110144, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32898563

RESUMO

BACKGROUND: Hypertension-related disease burden is a major challenge globally, with an estimated 1.56 billion adults expected to be affected by hypertension by 2025. Environmental factors, such as metals, could be risk factors for hypertension, but the relationship between airborne metals and hypertension is rarely studied. METHODS: Census-tract airborne metal concentrations (arsenic, cadmium, chromium, cobalt, lead, manganese, mercury, nickel, selenium, and antimony) from the U.S. Environmental Protection Agency 2005 National Air Toxics Assessment database were linked to enrollment residential addresses of 47,595 women in the Sister Study cohort. Hypertension was defined as high systolic (≥140 mm Hg) or diastolic (≥90 mm Hg) blood pressure measured by trained examiners at enrollment or taking anti-hypertensive medications. Multivariable log binomial regression was used to estimate adjusted prevalence ratios (PRs) and 95% confidence intervals (CIs) for the association between individual metals and hypertension, with and without co-adjustment for other metals. Quantile-based g-computation was used to estimate the joint effect of the overall metal mixture. RESULTS: Comparing the highest to lowest quartiles, risk of hypertension was higher among women with higher residential exposure to arsenic (PR = 1.05, 95%CI = 1.02,1.09), lead (PR = 1.04, 95%CI = 1.01,1.08), chromium (PR = 1.03, 95%CI = 1.00,1.06), cobalt (PR = 1.03, 95%CI = 1.00,1.07), and manganese (PR = 1.03, 95%CI = 1.00,1.06). Selenium was associated with lower risk of hypertension (PR = 0.96, 95%CI = 0.93,0.99). Results were similar with mutual adjustment for all other metals. The associations varied by race/ethnicity, with greater PRs in other races/ethnicities (Hispanic, black, and other participants) compared to non-Hispanic white participants. The joint effect of a quartile increase in exposure to all the metals was 1.02 (95%CI = 0.99,1.04). CONCLUSION: We found that living in areas of higher exposure to arsenic, lead, chromium, cobalt, and manganese was related to higher risk of hypertension, whereas living in areas with higher selenium was inversely related to the risk of hypertension.

10.
Artigo em Inglês | MEDLINE | ID: mdl-32917655

RESUMO

OBJECTIVE: This study compares the characteristics and place of death of patients with cancer receiving specialist palliative care in acute hospitals with those who do not. METHODS: All patients with incident invasive cancer in Ireland (1994-2016 inclusive), excluding non-melanoma skin cancer, who attended a cancer centre and died in 2016 were identified from cancer registry data. Patients were categorised based on a diagnosis code 'Encounter for palliative care' from linked hospital episode data. Place of death was categorised from death certificate data. Data were analysed using descriptive statistics, χ2 tests and logistic regression. RESULTS: Of n=4103 decedents identified, 62% had a hospital-based palliative care encounter in the year preceding death. Age (p<0.001), marital status (p=0.017), deprivation index (p<0.001) and health board region (p=0.008) were independent predictors of having a palliative care encounter. Place of death differed by palliative care encounter group: 45% of those with an encounter died in hospital versus 50% without an encounter, 33% vs 16% died in a hospice and 18% vs 28% died at home (p<0.001). CONCLUSION: Almost two-thirds of patients with cancer who attended a cancer centre and died in 2016 had a palliative care encounter. They were younger, less likely to be married and more likely to be from deprived areas. Having accounted for sociodemographic factors, there was evidence of regional variation in receiving care. Demographic and clinical factors and the provision of health services in a region need to be considered together when assessing end-of-life care.

11.
Artigo em Inglês | MEDLINE | ID: mdl-32960377

RESUMO

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.

12.
Cancer Epidemiol Biomarkers Prev ; 29(10): 2010-2018, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32732252

RESUMO

BACKGROUND: Epithelial ovarian, fallopian tube, and primary peritoneal cancers have shared developmental pathways. Few studies have prospectively examined heterogeneity in risk factor associations across these three anatomic sites. METHODS: We identified 3,738 ovarian, 337 peritoneal, and 176 fallopian tube incident cancer cases in 891,731 women from 15 prospective cohorts in the Ovarian Cancer Cohort Consortium. Associations between 18 putative risk factors and risk of ovarian, peritoneal, and fallopian tube cancer, overall and for serous and high-grade serous tumors, were evaluated using competing risks Cox proportional hazards regression. Heterogeneity was assessed by likelihood ratio tests. RESULTS: Most associations did not vary by tumor site (P het ≥ 0.05). Associations between first pregnancy (P het = 0.04), tubal ligation (P het = 0.01), and early-adult (age 18-21 years) body mass index (BMI; P het = 0.02) and risk differed between ovarian and peritoneal cancers. The association between early-adult BMI and risk further differed between peritoneal and fallopian tube cancer (P het = 0.03). First pregnancy and tubal ligation were inversely associated with ovarian, but not peritoneal, cancer. Higher early-adult BMI was associated with higher risk of peritoneal, but not ovarian or fallopian tube, cancer. Patterns were generally similar when restricted to serous and high-grade serous cases. CONCLUSIONS: Ovarian, fallopian tube, and primary peritoneal cancers appear to have both shared and distinct etiologic pathways, although most risk factors appear to have similar associations by anatomic site. IMPACT: Further studies on the mechanisms underlying the differences in risk profiles may provide insights regarding the developmental origins of tumors arising in the peritoneal cavity and inform prevention efforts.

13.
Environ Epidemiol ; 4(4): e0104, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32832842

RESUMO

Background: Menopause timing is related to cancer, cardiovascular disease, and mortality. Lead has been associated with an earlier age at menopause, but no study has considered exposure to other metals or multiple metals simultaneously. Methods: At baseline, we measured toenail concentrations of 16 metals for 903 premenopausal women in the Sister Study (2003-2009). Age at menopause was ascertained through follow-up questionnaires. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between individual metals and age at menopause. We used quantile-g-computation to examine the association between age at menopause and the joint effect of a simultaneous increase in (1) all metals and for subgroups of metals categorized as (2) essential or (3) non-essential. Results: For individual metals, we observed negligible associations except for an interquartile range increase in lead which was modestly associated with an earlier age at menopause (HR = 1.03, 95% CI = 1.01, 1.05). In the mixture analyses, a quartile increase in all metals was associated with a later age at menopause (HR = 0.81, 95% CI = 0.64, 1.02). The metals with the largest negative contributions (i.e., associated with a later age at menopause) were chromium and nickel. The joint effect for the essential metals remained inverse (HR = 0.83, 95% CI = 0.64, 1.07), but was attenuated for nonessential metals (HR = 0.98, 95% CI = 0.76, 1.24). Conclusions: Although no individual metal was strongly associated with age at menopause, our joint effect analysis suggests that having low levels of essential metals could be associated with an earlier age at menopause.

14.
Breast Cancer Res ; 22(1): 88, 2020 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-32791983

RESUMO

BACKGROUND: Perinatal factors have been associated with some adult health outcomes, but have not been well studied in young-onset breast cancer. We aimed to evaluate the association between young-onset breast cancer and perinatal exposures and to explore etiologic heterogeneity in the relationship between associated perinatal factors and estrogen receptor status of the tumor. METHODS: We addressed this in a sister-matched case-control study. Cases were women who had been diagnosed with ductal carcinoma in situ or invasive breast cancer before the age of 50. Each case had a sister control who was free of breast cancer up to the same age at which her case sister developed the disease. The factors considered were self-reported and included the mother's preeclampsia in that pregnancy, mother's smoking in that pregnancy, gestational hypertension, prenatal diethylstilbestrol use, and gestational diabetes, as well as low birth weight (less than 5.5 pounds), high birth weight (greater than 8.8 pounds), short gestational length (less than 38 completed weeks), and being breastfed or being fed soy formula. RESULTS: In conditional logistic regression analyses, high birth weight (odds ratio [OR] = 1.59, 95% confidence interval [CI] 1.07-2.36) and preeclampsia (adjusted OR = 1.92, CI 0.824-4.5162) were positively associated with risk. The association with preeclampsia was stronger when the analysis was restricted to invasive breast cancer (OR = 2.87, CI 1.08-7.59). We also used case-only analyses to assess etiologic heterogeneity for estrogen receptor (ER)-positive versus estrogen receptor-negative cancer. Women who were born to a preeclamptic pregnancy and later developed young-onset breast cancer were at increased odds for the ER-negative type (OR = 2.27; CI 1.05-4.92). CONCLUSION: These results suggest that being born to a preeclamptic pregnancy may increase risk for young-onset breast cancer, especially for the ER-negative subtype.

15.
Cancer Prev Res (Phila) ; 13(12): 1007-1016, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32727823

RESUMO

Periodontal disease may be associated with increased breast cancer risk, but studies have not considered invasive breast cancer and ductal carcinoma in situ (DCIS) separately in the same population. We assessed the relationship between periodontal disease and breast cancer in a large prospective cohort study. The Sister Study followed women without prior breast cancer ages 35 to 74 years from 2003 to 2017 (N = 49,968). Baseline periodontal disease was self-reported, and incident breast cancer was ascertained over a mean follow-up of 9.3 years. We estimated hazard ratios (HR) and 95% confidence intervals (CI) using Cox proportional hazards regression, adjusting for multiple potential confounders, including smoking status. Heterogeneity in risk for invasive breast cancer versus DCIS was also estimated. About 22% of participants reported a history of periodontal disease at baseline. A total of 3,339 incident breast cancers (2,607 invasive breast cancer, 732 DCIS) were identified. There was no clear association between periodontal disease and overall breast cancer risk (HR = 1.02; 95% CI, 0.94-1.11). However, we observed a nonstatistically significant suggestive increased risk of invasive breast cancer (HR = 1.07; 95% CI, 0.97-1.17) and decreased risk of DCIS (HR = 0.86; 95% CI, 0.72-1.04) associated with periodontal disease, with evidence for heterogeneity in the risk associations (relative HR for invasive breast cancer versus DCIS = 1.24; 95% CI, 1.01-1.52). A case-only analysis for etiologic heterogeneity confirmed this difference. We observed no clear association between periodontal disease and overall breast cancer risk. The heterogeneity in risk associations for invasive breast cancer versus DCIS warrants further exploration.

16.
JAMA ; 323(20): 2096-2097, 2020 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-32453361
17.
J Hepatol ; 73(4): 863-872, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32437829

RESUMO

BACKGROUND & AIMS: Gallbladder cancer (GBC) is known to have a female predominance while other biliary tract cancers (BTCs) have a male predominance. However, the role of female reproductive factors in BTC etiology remains unclear. METHODS: We pooled data from 19 studies of >1.5 million women participating in the Biliary Tract Cancers Pooling Project to examine the associations of parity, age at menarche, reproductive years, and age at menopause with BTC. Associations for age at menarche and reproductive years with BTC were analyzed separately for Asian and non-Asian women. Hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards models, stratified by study. RESULTS: During 21,681,798 person-years of follow-up, 875 cases of GBC, 379 of intrahepatic bile duct cancer (IHBDC), 450 of extrahepatic bile duct cancer (EHBDC), and 261 of ampulla of Vater cancer (AVC) occurred. High parity was associated with risk of GBC (HR ≥5 vs. 0 births 1.72; 95% CI 1.25-2.38). Age at menarche (HR per year increase 1.15; 95% CI 1.06-1.24) was associated with GBC risk in Asian women while reproductive years were associated with GBC risk (HR per 5 years 1.13; 95% CI 1.04-1.22) in non-Asian women. Later age at menarche was associated with IHBDC (HR 1.19; 95% CI 1.09-1.31) and EHBDC (HR 1.11; 95% CI 1.01-1.22) in Asian women only. CONCLUSION: We observed an increased risk of GBC with increasing parity. Among Asian women, older age at menarche was associated with increased risk for GBC, IHBDC, and EHBDC, while increasing reproductive years was associated with GBC in non-Asian women. These results suggest that sex hormones have distinct effects on cancers across the biliary tract that vary by geography. LAY SUMMARY: Our findings show that the risk of gallbladder cancer is increased among women who have given birth (especially women with 5 or more children). In women from Asian countries, later age at menarche increases the risk of gallbladder cancer, intrahepatic bile duct cancer and extrahepatic bile duct cancer. We did not see this same association in women from Western countries. Age at menopause was not associated with the risk of any biliary tract cancers.

18.
Artigo em Inglês | MEDLINE | ID: mdl-32329357

RESUMO

Objective: The majority of cases of the fatal neurodegenerative disease amyotrophic lateral sclerosis (ALS) are of unknown etiology. A proportion of these cases are likely to be attributable to contaminant exposures, although the specific environmental etiology of ALS remains largely a mystery. Certain forms of the neurotoxic metal mercury readily cross into the central nervous system. Fish is a dietary source of methylmercury, but also of beneficial components, such as omega-3 polyunsaturated fatty acids. Prior work using clinic-based studies of toenails and hair as keratinous biomarkers of exposure suggest elevated mercury levels in ALS patients compared with controls. We sought to validate this relationship in a U.S. case-control comparison of mercury levels in nail clippings. Methods: We performed trace element analysis using inductively coupled plasma mass spectrometry (ICP-MS) on the nail clippings of n = 70 female, geographically representative ALS patients from the National ALS Biorepository and compared them to n = 210 age-matched controls from a set of n = 1216 nationally distributed controls from the Sister and Two Sister Studies. Results: Compared to the lowest quartile of nail mercury, moderate levels were associated with decreased risk of ALS (P = 4.18e-6). However, the odds of having nail mercury levels above the 90th percentile were 2.3-fold higher among ALS patients compared with controls (odds ratio (OR) = 2.3, 95% confidence interval 1.10-4.58, adjusted for age and smoking status). Conclusion: This finding suggests that excessive mercury exposure may be associated with the neurodegenerative health of aging populations.

19.
Am J Epidemiol ; 2020 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-32242622

RESUMO

Cadmium is ovarian toxic in animal studies, but its association with diminished ovarian reserve in women is not established. We investigated urinary cadmium, a biomarker of long-term exposure, in relation to diminished ovarian reserve, as indicated by elevated serum follicle stimulating hormone concentrations (≥10 IU/L), in women ages 35-49 (unweighted n=1,681). Using data from the Third National Health and Nutrition Examination Survey, 1988-94, we conducted Poisson regression to estimate adjusted relative risks (RR) and 95% confidence intervals (CI). Because the best approach to correct for urinary dilution in spot samples with creatinine remains controversial, we employed three approaches: standardization, covariate adjustment, and covariate-adjusted standardization. Our data suggested a modest association with standardization (highest vs. lowest quartile: RR 1.3, 95% CI: 0.8, 1.9; Ptrend=0.06) and covariate-adjusted standardization (highest vs. lowest quartile: RR 1.3, 95% CI: 0.9, 1.9; Ptrend=0.05), and a stronger association with covariate adjustment (highest vs. lowest quartile: RR 1.8, 95% CI: 1.2, 2.9; Ptrend=0.01). The stronger association with covariate adjustment may reflect bias from conditioning on urinary creatinine, a collider in the hypothesized causal pathway. We conclude that cadmium may contribute to ovarian aging in women and that careful consideration of the creatinine-adjustment approach is needed to minimize bias.

20.
Cancer Epidemiol Biomarkers Prev ; 29(7): 1509-1511, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32317301

RESUMO

BACKGROUND: Gestational diabetes mellitus (GDM) has been hypothesized to increase breast cancer risk, but results from the few prior epidemiologic studies are conflicting, and no studies have examined the association in African American women. METHODS: We analyzed data from the prospective Black Women's Health Study to evaluate associations of history of GDM with breast cancer risk among 41,767 parous African American women, adjusting for potential confounders. HRs and 95% confidence intervals (CI) were estimated from multivariable Cox proportional hazards regression models. RESULTS: There was no evidence of an association between history of GDM and risk of invasive breast cancer, overall or by estrogen receptor status. CONCLUSIONS: Results of this study do not support the hypothesis that GDM is an important risk factor for breast cancer in African American women overall. IMPACT: On the basis of these data, breast cancer risk is not increased among African American women with a history of GDM compared with parous women without a history of GDM.

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