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1.
Cancer Causes Control ; 30(11): 1183-1200, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31471762

RESUMO

PURPOSE: The purpose of the present study was to systematically review the complex associations between energy balance-related factors and breast cancer risk, for which previous evidence has suggested different associations in the life course of women and by hormone receptor (HR) status of the tumor. METHODS: Relevant publications on adulthood physical activity, sedentary behavior, body mass index (BMI), waist and hip circumferences, waist-to-hip ratio, and weight change and pre- and postmenopausal breast cancer risk were identified in PubMed up to 30 April 2017. Random-effects meta-analyses were conducted to summarize the relative risks across studies. RESULTS: One hundred and twenty-six observational cohort studies comprising over 22,900 premenopausal and 103,000 postmenopausal breast cancer cases were meta-analyzed. Higher physical activity was inversely associated with both pre- and postmenopausal breast cancers, whereas increased sitting time was positively associated with postmenopausal breast cancer. Although higher early adult BMI (ages 18-30 years) was inversely associated with pre- and postmenopausal breast cancers, adult weight gain and greater body adiposity increased breast cancer risk in postmenopausal women, and the increased risk was evident for HR+ but not HR- breast cancers, and among never but not current users of postmenopausal hormones. The evidence was less consistent in premenopausal women. There were no associations with adult weight gain, inverse associations with adult BMI (study baseline) and hip circumference, and non-significant associations with waist circumference and waist-to-hip ratio that were reverted to positive associations on average in studies accounting for BMI. No significant associations were observed for HR-defined premenopausal breast cancers. CONCLUSION: Better understanding on the impact of these factors on pre- and postmenopausal breast cancers and their subtypes along the life course is needed.

3.
Cancer ; 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31415710

RESUMO

BACKGROUND: Discrimination and trust are known barriers to accessing health care. Despite well-documented racial disparities in the ovarian cancer care continuum, the role of these barriers has not been examined. This study evaluated the association of everyday discrimination and trust in physicians with a prolonged interval between symptom onset and ovarian cancer diagnosis (hereafter referred to as prolonged symptom duration). METHODS: Subjects included cases enrolled in the African American Cancer Epidemiology Study, a multisite case-control study of epithelial ovarian cancer among black women. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for associations of everyday discrimination and trust in physicians with a prolonged symptom duration (1 or more symptoms lasting longer than the median symptom-specific duration), and it controlled for access-to-care covariates and potential confounders. RESULTS: Among the 486 cases in this analysis, 302 women had prolonged symptom duration. In the fully adjusted model, a 1-unit increase in the frequency of everyday discrimination increased the odds of prolonged symptom duration 74% (OR, 1.74; 95% CI, 1.22-2.49), but trust in physicians was not associated with prolonged symptom duration (OR, 0.86; 95% CI, 0.66-1.11). CONCLUSIONS: Perceived everyday discrimination was associated with prolonged symptom duration, whereas more commonly evaluated determinants of access to care and trust in physicians were not. These results suggest that more research on the effects of interpersonal barriers affecting ovarian cancer care is warranted.

4.
Public Health Nutr ; : 1-11, 2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31439055

RESUMO

OBJECTIVE: To examine adherence to a Mediterranean-like diet at age 9-10 years in relation to onset of breast development (thelarche) and first menstruation (menarche). DESIGN: We evaluated the associations of adherence to a Mediterranean-like diet (measured by an adapted Mediterranean-like Diet Score, range 0-9) with thelarche at baseline, age at thelarche and time to menarche. Data were collected at baseline during a clinic visit, complemented with a mailed questionnaire and three 24 hour telephone dietary recalls, followed by annual follow-up questionnaires. Multivariable Poisson regression, linear regression and Cox proportional hazards regression were used to evaluate timing of pubertal development in relation to diet adherence. SETTING: New Jersey, USA. PARTICIPANTS: Girls aged 9 or 10 years at baseline (2006-2014, n 202). RESULTS: High Mediterranean-like diet adherence (score 6-9) was associated with a lower prevalence of thelarche at baseline compared with low adherence (score 0-3; prevalence ratio = 0·65, 95 % CI 0·48, 0·90). This may have been driven by consumption of fish and non-fat/low-fat dairy. Our models also suggested a later age at thelarche with higher Mediterranean-like diet adherence. Girls with higher Mediterranean-like diet adherence had significantly longer time to menarche (hazard ratio = 0·45, 95 % CI 0·28, 0·71 for high v. low adherence). Further analysis suggested this may have been driven by vegetable and non-fat/low-fat dairy consumption. CONCLUSIONS: Consuming a Mediterranean-like diet may be associated with older age at thelarche and menarche. Further research is necessary to confirm our findings in other US paediatric populations and elucidate the mechanism through which Mediterranean-like diet may influence puberty timing.

5.
Int J Cancer ; 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31469419

RESUMO

Women of African ancestry have lower incidence of epithelial ovarian cancer (EOC) yet worse survival compared to women of European ancestry. We conducted a genome-wide association study in African ancestry women with 755 EOC cases, including 537 high-grade serous ovarian carcinomas (HGSOC) and 1,235 controls. We identified four novel loci with suggestive evidence of association with EOC (p < 1 × 10-6 ), including rs4525119 (intronic to AKR1C3), rs7643459 (intronic to LOC101927394), rs4286604 (12 kb 3' of UGT2A2) and rs142091544 (5 kb 5' of WWC1). For HGSOC, we identified six loci with suggestive evidence of association including rs37792 (132 kb 5' of follistatin [FST]), rs57403204 (81 kb 3' of MAGEC1), rs79079890 (LOC105376360 intronic), rs66459581 (5 kb 5' of PRPSAP1), rs116046250 (GABRG3 intronic) and rs192876988 (32 kb 3' of GK2). Among the identified variants, two are near genes known to regulate hormones and diseases of the ovary (AKR1C3 and FST), and two are linked to cancer (AKR1C3 and MAGEC1). In follow-up studies of the 10 identified variants, the GK2 region SNP, rs192876988, showed an inverse association with EOC in European ancestry women (p = 0.002), increased risk of ER positive breast cancer in African ancestry women (p = 0.027) and decreased expression of GK2 in HGSOC tissue from African ancestry women (p = 0.004). A European ancestry-derived polygenic risk score showed positive associations with EOC and HGSOC in women of African ancestry suggesting shared genetic architecture. Our investigation presents evidence of variants for EOC shared among European and African ancestry women and identifies novel EOC risk loci in women of African ancestry.

6.
Int J Epidemiol ; 48(3): 822-830, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-31211375

RESUMO

BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex endocrine disorder with an estimated prevalence of 4-21% in reproductive aged women. Recently, the Ovarian Cancer Association Consortium (OCAC) reported a decreased risk of invasive ovarian cancer among women with self-reported PCOS. However, given the limitations of self-reported PCOS, the validity of these observed associations remains uncertain. Therefore, we sought to use Mendelian randomization with genetic markers as a proxy for PCOS, to examine the association between PCOS and ovarian cancer. METHODS: Utilizing 14 single nucleotide polymorphisms (SNPs) previously associated with PCOS we assessed the association between genetically predicted PCOS and ovarian cancer risk, overall and by histotype, using summary statistics from a previously conducted genome-wide association study (GWAS) of ovarian cancer among European ancestry women within the OCAC (22 406 with invasive disease, 3103 with borderline disease and 40 941 controls). RESULTS: An inverse association was observed between genetically predicted PCOS and invasive ovarian cancer risk: odds ratio (OR)=0.92 [95% confidence interval (CI)=0.85-0.99; P = 0.03]. When results were examined by histotype, the strongest inverse association was observed between genetically predicted PCOS and endometrioid tumors (OR = 0.77; 95% CI = 0.65-0.92; P = 0.003). Adjustment for individual-level body mass index, oral contraceptive use and parity did not materially change the associations. CONCLUSION: Our study provides evidence for a relationship between PCOS and reduced ovarian cancer risk, overall and among specific histotypes of invasive ovarian cancer. These results lend support to our previous observational study results. Future studies are needed to understand mechanisms underlying this association.

7.
Cancer Causes Control ; 30(9): 967-978, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31236792

RESUMO

PURPOSE: Although the incidence rate of epithelial ovarian cancer (EOC) is somewhat lower in African American (AA) than white women, survival is worse. The Ovarian Cancer in Women of African Ancestry (OCWAA) consortium will overcome small, study-specific sample sizes to better understand racial differences in EOC risk and outcomes. METHODS: We harmonized risk factors and prognostic characteristics from eight U.S. STUDIES: the North Carolina Ovarian Cancer Study (NCOCS), the Los Angeles County Ovarian Cancer Study (LACOCS), the African American Cancer Epidemiology Study (AACES), the Cook County Case-Control Study (CCCCS), the Black Women's Health Study (BWHS), the Women's Health Initiative (WHI), the Multiethnic Cohort Study (MEC), and the Southern Community Cohort Study (SCCS). RESULTS: Determinants of disparities for risk and survival in 1,146 AA EOC cases and 2,922 AA controls will be compared to 3,368 white EOC cases and 10,270 white controls. Analyses include estimation of population-attributable risk percent (PAR%) by race. CONCLUSION: OCWAA is uniquely positioned to study the epidemiology of EOC in AA women compared with white women to address disparities. Studies of EOC have been underpowered to address factors that may explain AA-white differences in the incidence and survival. OCWAA promises to provide novel insight into disparities in ovarian cancer.


Assuntos
Neoplasias Ovarianas/etnologia , Neoplasias Ovarianas/epidemiologia , Adulto , Afro-Americanos , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Estudos de Coortes , Grupo com Ancestrais do Continente Europeu , Feminino , Humanos , Illinois/epidemiologia , Incidência , Pessoa de Meia-Idade , North Carolina/epidemiologia , Fatores de Risco , Estados Unidos , Adulto Jovem
8.
J Nutr ; 149(9): 1606-1616, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31152675

RESUMO

BACKGROUND: Chronic inflammation is associated with ovarian carcinogenesis; yet, the impact of inflammatory-related exposures on outcomes has been understudied. OBJECTIVE: Given the poor survival of women diagnosed with ovarian cancer, especially African-Americans, we examined whether diet-associated inflammation, a modifiable source of chronic systemic inflammation measured by the dietary inflammatory index (DII), was associated with all-cause mortality among African-American women with ovarian carcinoma. METHODS: Data were available from 490 ovarian carcinoma patients enrolled in a population-based case-control study of African-American women with ovarian cancer, the African-American Cancer Epidemiology Study. Energy-adjusted DII (E-DII) scores were calculated based on prediagnostic dietary intake of foods alone or foods and supplements, which was self-reported using the 2005 Block Food Frequency Questionnaire. Cox proportional hazards regression was used to estimate risk of mortality overall and for the most common histotype, high-grade serous carcinoma. Additionally, we assessed interaction by age at diagnosis and smoking status. RESULTS: Women included in this study had a median age of 57 y, and the majority of women were obese (58%), had late-stage disease (Stage III or IV, 66%), and had high-grade serous carcinoma (64%). Greater E-DII scores including supplements (indicating greater inflammatory potential) were associated with an increased risk of mortality among women with high-grade serous carcinoma (HR1-unit change: 1.08; 95% CI: 1.01, 1.17). Similar associations were observed for the E-DII excluding supplements, although not statistically significant (HR1-unit change: 1.07; 95% CI: 0.97, 1.17). There was an interaction by smoking status, where the positive association with mortality was present only among ever smokers (HRQuartile 4/Quartile 1: 2.36; 95% CI: 1.21, 4.60) but not among never smokers. CONCLUSIONS: Greater inflammatory potential of prediagnostic diet may adversely impact prognosis among African-American women with high-grade serous carcinoma, and specifically among ever smokers.

9.
Cancer Med ; 8(5): 2503-2513, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31001917

RESUMO

An association between genetic variants in the vitamin D receptor (VDR) gene and epithelial ovarian cancer (EOC) was previously reported in women of African ancestry (AA). We sought to examine associations between genetic variants in VDR and additional genes from vitamin D biosynthesis and pathway targets (EGFR, UGT1A, UGT2A1/2, UGT2B, CYP3A4/5, CYP2R1, CYP27B1, CYP24A1, CYP11A1, and GC). Genotyping was performed using the custom-designed 533,631 SNP Illumina OncoArray with imputation to the 1,000 Genomes Phase 3 v5 reference set in 755 EOC cases, including 537 high-grade serous (HGSOC), and 1,235 controls. All subjects are of African ancestry (AA). Logistic regression was performed to estimate odds ratios (OR) and 95% confidence intervals (CI). We further evaluated statistical significance of selected SNPs using the Bayesian False Discovery Probability (BFDP). A significant association with EOC was identified in the UGT2A1/2 region for the SNP rs10017134 (per allele OR = 1.4, 95% CI = 1.2-1.7, P = 1.2 × 10-6 , BFDP = 0.02); and an association with HGSOC was identified in the EGFR region for the SNP rs114972508 (per allele OR = 2.3, 95% CI = 1.6-3.4, P = 1.6 × 10-5 , BFDP = 0.29) and in the UGT2A1/2 region again for rs1017134 (per allele OR = 1.4, 95% CI = 1.2-1.7, P = 2.3 × 10-5 , BFDP = 0.23). Genetic variants in the EGFR and UGT2A1/2 may increase susceptibility of EOC in AA women. Future studies to validate these findings are warranted. Alterations in EGFR and UGT2A1/2 could perturb enzyme efficacy, proliferation in ovaries, impact and mark susceptibility to EOC.

10.
Environ Health ; 18(1): 24, 2019 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-30902092

RESUMO

BACKGROUND: Despite evidence of the endocrine disrupting properties of zearalenone (ZEN) and alpha-zearalanol (zeranol, α-ZAL), they have been minimally studied in human populations. In previous cross-sectional analyses, we demonstrated that 9-10 years old girls with detectable urinary ZEN were of shorter stature and less likely to have reached the onset of breast development than girls with undetectable urinary ZEN. The aim of this study was to examine baseline concentrations of ZEN, (α-ZAL), and their phase-1 metabolites in relation to subsequent growth and timing of menarche using 10 years of longitudinal data. METHODS: Urine samples were collected from participants in the Jersey Girl Study at age 9-10 (n = 163). Unconjugated ZEN, (α-ZAL), and their metabolites were analyzed using high performance liquid chromatography and tandem mass spectrometry. Information on height, weight, and pubertal development was collected at a baseline visit with annual follow-up by mail thereafter. Cox regression was used to evaluate time to menarche in relation to baseline ZEN, (α-ZAL), and total mycoestrogen exposure. Z-scores for height and weight were used in mixed models to assess growth. RESULTS: Mycoestrogens were detectable in urine in 78.5% of the girls (median ZEN: 1.02 ng/ml, range 0-22.3). Girls with detectable urinary concentrations of (α-ZAL) and total mycoestrogens (sum of ZEN, (α-ZAL) and their metabolites) at baseline were significantly shorter at menarche than girls with levels below detection (p = 0.04). ZEN and total mycoestrogen concentrations were inversely associated with height- and weight-z-scores at menarche (adjusted ß = - 0.18, 95% CI: -0.29, - 0.08, and adjusted ß = - 0.10, 95% CI: -0.21, 0.01, respectively). CONCLUSION: This study supports and extends our previous results suggesting that exposure to ZEN, (α-ZAL), and their metabolites is associated with slower growth and pubertal development in adolescent girls.


Assuntos
Disruptores Endócrinos/urina , Estrogênios/urina , Desenvolvimento Sexual , Zearalenona/urina , Zeranol/urina , Estatura , Peso Corporal , Criança , Monitoramento Ambiental , Feminino , Humanos , New Jersey
11.
Cancer Causes Control ; 30(5): 537-547, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30905014

RESUMO

PURPOSE: Previous epidemiologic studies have shown that smoking, obesity, and physical inactivity are associated with poor survival following a diagnosis of ovarian cancer. Yet, the combined relationship of these unfavorable lifestyle factors on ovarian cancer survival has not been sufficiently investigated. METHODS: Using data pooled from 13 studies, we examined the associations between combined exposures to smoking, overweight/obesity weight, and physical inactivity and overall survival (OS) as well as progression-free survival (PFS) among women diagnosed with invasive epithelial ovarian carcinoma (n = 7,022). Using age- and stage-adjusted Cox proportional hazards regression models, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) associated with joint exposure to these factors. RESULTS: Combined exposure to current smoking, overweight/obesity, and physical inactivity prior to diagnosis was associated with a significantly increased risk of mortality compared to women who never smoked, had normal body mass index (BMI), and were physically active (HR = 1.37; 95% CI 1.10-1.70). The association for a joint exposure to these factors exceeded that of each exposure individually. In fact, exposure to both current smoking and overweight/obesity, and current smoking and physical inactivity was also associated with increased risk of death (HR = 1.28; 95% CI 1.08-1.52, and HR = 1.26; 95% CI 1.04-1.54, respectively). The associations were of a similar magnitude when former smoking was assessed in combination with the other exposures and when excessive weight was limited to obesity only. No significant associations were observed between joint exposure to any of these factors and PFS. CONCLUSIONS: Joint exposure to smoking, excessive weight, and physical inactivity may negatively impact survival of ovarian cancer patients. These results suggest the importance of examining the combined effect of lifestyle factors on ovarian cancer patients' survival.


Assuntos
Carcinoma Epitelial do Ovário/epidemiologia , Neoplasias Ovarianas/epidemiologia , Comportamento Sedentário , Fumar/epidemiologia , Feminino , Humanos , Atividade Motora , Obesidade/complicações , Neoplasias Ovarianas/mortalidade , Sobrepeso/complicações , Modelos de Riscos Proporcionais , Fatores de Risco , Fumar/efeitos adversos , Ganho de Peso
12.
Nat Commun ; 10(1): 431, 2019 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-30683880

RESUMO

Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (rg = 0.57, p = 4.6 × 10-8), breast and ovarian cancer (rg = 0.24, p = 7 × 10-5), breast and lung cancer (rg = 0.18, p =1.5 × 10-6) and breast and colorectal cancer (rg = 0.15, p = 1.1 × 10-4). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis.


Assuntos
Neoplasias da Mama/genética , Neoplasias Colorretais/genética , Neoplasias de Cabeça e Pescoço/genética , Padrões de Herança , Neoplasias Pulmonares/genética , Neoplasias Ovarianas/genética , Neoplasias da Próstata/genética , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/etnologia , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/etnologia , Neoplasias Colorretais/patologia , Grupo com Ancestrais do Continente Europeu , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/etnologia , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/etnologia , Neoplasias Pulmonares/patologia , Masculino , Transtornos Mentais/etnologia , Transtornos Mentais/genética , Transtornos Mentais/fisiopatologia , Proteínas de Neoplasias/genética , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/etnologia , Neoplasias Ovarianas/patologia , Fenótipo , Polimorfismo de Nucleotídeo Único , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/etnologia , Neoplasias da Próstata/patologia , Fumar/etnologia , Fumar/genética , Fumar/fisiopatologia
13.
Int J Cancer ; 2018 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-30499236

RESUMO

As a follow-up to genome-wide association analysis of common variants associated with ovarian carcinoma (cancer), this study considers seven well-known ovarian cancer risk factors and their interactions with 28 genome-wide significant common genetic variants. The interaction analyses were based on data from 9,971 ovarian cancer cases and 15,566 controls from 17 case-control studies. Likelihood ratio and Wald tests for multiplicative interaction and for relative excess risk due to additive interaction were used. The top multiplicative interaction was noted between oral contraceptive pill (OCP) use (ever vs never) and rs13255292 (P-value = 3.48 x 10-4 ). Among women with the TT genotype for this variant, the odds ratio for OCP use was 0.53 (95% CI=0.46-0.60) compared to 0.71 (95%CI=0.66-0.77) for women with the CC genotype. When stratified by duration of OCP use, women with 1-5 years of OCP use exhibited differential protective benefit across genotypes. However, no interaction on either the multiplicative or additive scale was found to be statistically significant after multiple testing correction. The results suggest that OCP use may offer increased benefit for women who are carriers of the T allele in rs13255292. On the other hand, for women carrying the C allele in this variant, longer (5+ years) use of OCP may reduce the impact of carrying the risk allele of this SNP. Replication of this finding is needed. The study presents a comprehensive analytic framework for conducting gene-environment analysis in ovarian cancer. This article is protected by copyright. All rights reserved.

14.
Transl Behav Med ; 2018 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-30535101

RESUMO

Weight management after breast cancer (BC) treatment in African American (AA) women is crucial to reduce comorbid conditions and health disparities. We examined feasibility and potential efficacy of commercial eHealth/mHealth tools for weight management in AA BC survivors in New Jersey. Participants (N = 35) were randomized to an intervention (SparkPeople) plus activity tracker, Fitbit Charge (n = 18), or wait-list active control group (Fitbit only, n = 17). Anthropometric, behavioral, and quality of life (QOL) outcomes were collected at baseline, 3, 6, and 12 months. Differences in outcomes were assessed using intent-to-treat analysis. Retention was 97.1%. Both groups lost weight, with no significant differences between groups. At month 6, mean weight change was: intervention: -1.71 kg (SD 2.33; p = .006), 33.3% lost ≥3% of baseline weight; control: -2.54 kg (SD 4.00, p = .002), 23.5% lost ≥3% weight. Intervention participants achieved significant improvements in waist circumference (-3.56 cm, SD 4.70, p = .005), QOL (p = .030), and use of strategies for healthy eating (p = .025) and decreasing calories (p < .001). Number of days logged food per week was associated with decreases in waist circumference at 6 months (ß -0.79, 95% CI, -1.49, -0.09, p = .030) and 12 months (ß -2.16, 95% CI, -4.17, -0.15, p = .038). Weight loss was maintained at 12 months. This is the first study to demonstrate potential efficacy of commercial eHealth/mHealth tools for weight loss in AA BC survivors, without additional counseling from the research team. If effective, they may be convenient weight loss tools that can be easily and widely disseminated. Clinical Trials registration: ClinicalTrials.gov NCT02699983.

15.
Artigo em Inglês | MEDLINE | ID: mdl-30481095

RESUMO

BACKGROUND: Certain cultural, folk, and religious beliefs that are more common among African Americans (AAs) have been associated with later-stage breast cancer. It is unknown if these beliefs are similarly associated with delays in diagnosis of ovarian cancer. METHODS: Data from a multicenter case-control study of ovarian cancer in AA women were used to examine associations between cultural/folk beliefs and religious practices and stage at diagnosis and symptom duration before diagnosis. Associations between cultural/folk beliefs or religious practices and stage at diagnosis were assessed with logistic regression analyses, and associations with symptom duration with linear regression analyses. RESULTS: Agreement with several of the cultural/folk belief statements was high (e.g., 40% agreed that "if a person prays about cancer, God will heal it without medical treatments"), and ∼90% of women expressed moderate to high levels of religiosity/spirituality. Higher levels of religiosity/spirituality were associated with a twofold increase in the odds of stage III-IV ovarian cancer, whereas agreement with the cultural/folk belief statements was not associated with stage. Symptom duration before diagnosis was not consistently associated with cultural/folk beliefs or religiosity/spirituality. CONCLUSIONS: Women who reported stronger religious beliefs or practices had increased odds of higher stage ovarian cancer. Inaccurate cultural/folk beliefs about cancer treament were not associated with stage; however, these beliefs were highly prevalent in our population and could impact patient treatment decisions. Our findings suggest opportunities for health education interventions, especially working with churches, and improved doctor-patient communication.

16.
Cancer Causes Control ; 29(11): 1081-1091, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30269307

RESUMO

BACKGROUND: The association between common benign gynecologic conditions and ovarian cancer remains under-studied in African Americans. Therefore, we examine the association between self-reported history of benign gynecologic conditions and epithelial ovarian cancer risk in African-American women. METHODS: Data from a large population-based, multi-center case-control study of epithelial ovarian cancer in African-American women were analyzed to estimate the association between self-reported history of endometriosis, pelvic inflammatory disease (PID), fibroid, and ovarian cyst with epithelial ovarian cancer. Logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI) for the associations between individual and composite gynecologic conditions and ovarian cancer. RESULTS: 600 cases and 752 controls enrolled in the African American Cancer Epidemiology Study between 1 December 2010 and 31 December 2015 comprised the study population. After adjusting for potential confounders, a history of endometriosis was associated with ovarian cancer (OR 1.78; 95% CI 1.09-2.90). A non-significant association of similar magnitude was observed with PID (OR 1.33; 95% CI 0.82-2.16), while no association was observed in women with a history of fibroid or ovarian cyst. A positive trend was observed for an increasing number of reported gynecologic conditions (p = 0.006) with consistency across histologic subtypes and among both oral contraceptive users and non-users. CONCLUSION: A self-reported history of endometriosis among African-American women was associated with increased risk of ovarian cancer. Having multiple benign gynecologic conditions also increased ovarian cancer risk.

17.
Artigo em Inglês | MEDLINE | ID: mdl-30307782

RESUMO

OBJECTIVE: While the incidence of epithelial ovarian cancer (EOC) is lower among African American (AA) women compared with European American (EA) women, AA women have markedly worse outcomes. In this study, we describe individual, social, and societal factors in health-related quality of life (HRQL) in AA women diagnosed with EOC in the African American Cancer Epidemiology Study (AACES) that we hypothesize may influence a patient's capacity to psychosocially adjust to a diagnosis of cancer. METHODS: There were 215 invasive EOC cases included in the analysis. HRQL was measured using the SF-8 component scores for physical (PCS) and mental (MCS) health. We used least squares regression to test the effects of individual dispositional factors (optimism and trait anxiety); social level (perceived social support); and societal-level factors (SES defined as low family income and low educational attainment, and perceived discrimination) on HRQL, while adjusting for patient age, tumor stage, body mass index, and comorbidity. Mediation analysis was applied to test whether social support and physical activity buffer impacts of EOC on HRQL. RESULTS: Optimism, trait anxiety, social support, poverty, and past perceived discrimination were significantly associated with HRQL following diagnosis of EOC. Specifically, higher family income, lower phobic anxiety, and higher social support were associated with better wellbeing on the MCS and PCS (p < 0.01). Higher perceived discrimination was associated with both lower MCS and PCS, whereas higher optimism was associated with higher MCS. Physical activity (MET-min/week) and social support displayed significant overall mediation for effects of SES on MCS and PCS, but not for trait anxiety. CONCLUSIONS: Both pre- and postdiagnosis characteristics of AA women with EOC are important predictors of HRQL after cancer diagnosis. Individual, social, and societal-level factors each contribute to HRQL status with EOC and should be assessed.

18.
Cancer Res ; 78(18): 5419-5430, 2018 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-30054336

RESUMO

Large-scale genome-wide association studies (GWAS) have identified approximately 35 loci associated with epithelial ovarian cancer (EOC) risk. The majority of GWAS-identified disease susceptibility variants are located in noncoding regions, and causal genes underlying these associations remain largely unknown. Here, we performed a transcriptome-wide association study to search for novel genetic loci and plausible causal genes at known GWAS loci. We used RNA sequencing data (68 normal ovarian tissue samples from 68 individuals and 6,124 cross-tissue samples from 369 individuals) and high-density genotyping data from European descendants of the Genotype-Tissue Expression (GTEx V6) project to build ovarian and cross-tissue models of genetically regulated expression using elastic net methods. We evaluated 17,121 genes for their cis-predicted gene expression in relation to EOC risk using summary statistics data from GWAS of 97,898 women, including 29,396 EOC cases. With a Bonferroni-corrected significance level of P < 2.2 × 10-6, we identified 35 genes, including FZD4 at 11q14.2 (Z = 5.08, P = 3.83 × 10-7, the cross-tissue model; 1 Mb away from any GWAS-identified EOC risk variant), a potential novel locus for EOC risk. All other 34 significantly associated genes were located within 1 Mb of known GWAS-identified loci, including 23 genes at 6 loci not previously linked to EOC risk. Upon conditioning on nearby known EOC GWAS-identified variants, the associations for 31 genes disappeared and three genes remained (P < 1.47 × 10-3). These data identify one novel locus (FZD4) and 34 genes at 13 known EOC risk loci associated with EOC risk, providing new insights into EOC carcinogenesis.Significance: Transcriptomic analysis of a large cohort confirms earlier GWAS loci and reveals FZD4 as a novel locus associated with EOC risk. Cancer Res; 78(18); 5419-30. ©2018 AACR.

20.
PLoS One ; 13(7): e0197561, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29979793

RESUMO

Epithelial ovarian cancer (EOC) is the fifth leading cause of cancer mortality in American women. Normal ovarian physiology is intricately connected to small GTP binding proteins of the Ras superfamily (Ras, Rho, Rab, Arf, and Ran) which govern processes such as signal transduction, cell proliferation, cell motility, and vesicle transport. We hypothesized that common germline variation in genes encoding small GTPases is associated with EOC risk. We investigated 322 variants in 88 small GTPase genes in germline DNA of 18,736 EOC patients and 26,138 controls of European ancestry using a custom genotype array and logistic regression fitting log-additive models. Functional annotation was used to identify biofeatures and expression quantitative trait loci that intersect with risk variants. One variant, ARHGEF10L (Rho guanine nucleotide exchange factor 10 like) rs2256787, was associated with increased endometrioid EOC risk (OR = 1.33, p = 4.46 x 10-6). Other variants of interest included another in ARHGEF10L, rs10788679, which was associated with invasive serous EOC risk (OR = 1.07, p = 0.00026) and two variants in AKAP6 (A-kinase anchoring protein 6) which were associated with risk of invasive EOC (rs1955513, OR = 0.90, p = 0.00033; rs927062, OR = 0.94, p = 0.00059). Functional annotation revealed that the two ARHGEF10L variants were located in super-enhancer regions and that AKAP6 rs927062 was associated with expression of GTPase gene ARHGAP5 (Rho GTPase activating protein 5). Inherited variants in ARHGEF10L and AKAP6, with potential transcriptional regulatory function and association with EOC risk, warrant investigation in independent EOC study populations.

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