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1.
Artigo em Inglês | MEDLINE | ID: mdl-31727725

RESUMO

BACKGROUND: As the stronger association of obesity with postmenopausal breast cancer in Asian than white women may be due to body fat distribution, we examined the relation of adiposity measures with percent mammographic density (PMD), a strong predictor of breast cancer incidence. METHODS: A total of 938 women from five ethnic groups (69.1±2.7 years) in the Adiposity Phenotype Study (APS) underwent DXA and MRI imaging. PMD was assessed in routine mammograms using a computer-assisted method. Spearman correlation coefficients were computed and general linear models were applied to estimate regression coefficients (ß) for PMD per 0.5 SD units of adiposity measures while adjusting for known confounders including DXA total body fat. RESULTS: For 701 (75%) of the participants (69.1±2.7 years), valid mammograms were obtained. Whereas total body fat, the trunk-to-periphery-fat ratio (TPFR), visceral fat (VAT), and subcutaneous fat (SAT) were inversely correlated with PMD (p<0.0001), the VAT/SAT ratio correlated positively (rspearman=0.10; p=0.01). In fully adjusted models, PMD remained inversely related to TPFR and SAT and disappeared for VAT, while it was strengthened for VAT/SAT (ß=0.51; p=0.009). This relation was stronger in Japanese Americans than other ethnic groups. CONCLUSION: This is the first study to show an association of a high VAT/SAT ratio with greater PMD, a marker of breast cancer risk after taking into account total body fat. IMPACT: The results indicate a link between the propensity to accumulate VAT and the amount of fat in the breast (1-PMD), which may influence the relation of obesity with breast cancer incidence.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31756444

RESUMO

BACKGROUND & AIMS: Esophageal adenocarcinoma (EAC) occurs most frequently in men. We performed a Mendelian randomization analysis to investigate whether genetic factors that regulate levels of sex hormones associated with risk of EAC or Barrett's esophagus (BE). METHODS: We conducted a Mendelian randomization analysis using data from patients with EAC (n=2488) or BE (n=3247) and control participants (n=2127), included in international consortia of genome-wide association studies in Australia, Europe, and North America. Genetic risk scores or single nucleotide variants were used as instrumental variables for 9 specific sex hormones. Logistic regression provided odds ratios (ORs) with 95% CIs. RESULTS: Higher genetically predicted levels of follicle stimulating hormones were associated with increased risks of EAC and/or BE in men (OR, 1.14 per allele increase; 95% CI, 1.01-1.27) and in women (OR, 1.28; 95% CI, 1.03-1.59). Higher predicted levels of luteinizing hormone were associated with a decreased risk of EAC in men (OR, 0.92 per standard deviation increase; 95% CI, 0.87-0.99) and in women (OR, 0.93; 95% CI, 0.79-1.09), and decreased risks of BE (OR, 0.88; 95% CI, 0.77-0.99) and EAC and/or BE (OR, 0.89; 95% CI, 0.79-1.00) in women. We found no clear associations for other hormones studied, including sex hormone-binding globulin, dehydroepiandrosterone sulphate, testosterone, dihydrotestosterone, estradiol, progesterone, or free androgen index. CONCLUSIONS: In a Mendelian randomization analysis of data from patients with EAC or BE, we found an association between genetically predicted levels of follicle stimulating and luteinizing hormones and risk of BE and EAC.

3.
EBioMedicine ; 48: 203-211, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31629678

RESUMO

BACKGROUND: We previously conducted a systematic field synopsis of 1059 breast cancer candidate gene studies and investigated 279 genetic variants, 51 of which showed associations. The major limitation of this work was the small sample size, even pooling data from all 1059 studies. Thereafter, genome-wide association studies (GWAS) have accumulated data for hundreds of thousands of subjects. It's necessary to re-evaluate these variants in large GWAS datasets. METHODS: Of these 279 variants, data were obtained for 228 from GWAS conducted within the Asian Breast Cancer Consortium (24,206 cases and 24,775 controls) and the Breast Cancer Association Consortium (122,977 cases and 105,974 controls of European ancestry). Meta-analyses were conducted to combine the results from these two datasets. FINDINGS: Of those 228 variants, an association was observed for 12 variants in 10 genes at a Bonferroni-corrected threshold of P < 2·19 × 10-4. The associations for four variants reached P < 5 × 10-8 and have been reported by previous GWAS, including rs6435074 and rs6723097 (CASP8), rs17879961 (CHEK2) and rs2853669 (TERT). The remaining eight variants were rs676387 (HSD17B1), rs762551 (CYP1A2), rs1045485 (CASP8), rs9340799 (ESR1), rs7931342 (CHR11), rs1050450 (GPX1), rs13010627 (CASP10) and rs9344 (CCND1). Further investigating these 10 genes identified associations for two additional variants at P < 5 × 10-8, including rs4793090 (near HSD17B1), and rs9210 (near CYP1A2), which have not been identified by previous GWAS. INTERPRETATION: Though most candidate gene variants were not associated with breast cancer risk, we found 14 variants showing an association. Our findings warrant further functional investigation of these variants. FUND: National Institutes of Health.

4.
Cancer ; 125(23): 4210-4223, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31490550

RESUMO

BACKGROUND: Diabetes is positively associated with various cancers, but its relationship with tumors of the esophagus/esophagogastric junction remains unclear. METHODS: Data were harmonized across 13 studies in the International Barrett's and Esophageal Adenocarcinoma Consortium, comprising 2309 esophageal adenocarcinoma (EA) cases, 1938 esophagogastric junction adenocarcinoma (EGJA) cases, 1728 Barrett's esophagus (BE) cases, and 16,354 controls. Logistic regression was used to estimate study-specific odds ratios (ORs) and 95% CIs for self-reported diabetes in association with EA, EGJA, and BE. Adjusted ORs were then combined using random-effects meta-analysis. RESULTS: Diabetes was associated with a 34% increased risk of EA (OR, 1.34; 95% CI, 1.00-1.80; I2  = 48.8% [where 0% indicates no heterogeneity, and larger values indicate increasing heterogeneity between studies]), 27% for EGJA (OR, 1.27; 95% CI, 1.05-1.55; I2  = 0.0%), and 30% for EA/EGJA combined (OR, 1.30; 95% CI, 1.06-1.58; I2  = 34.9%). Regurgitation symptoms modified the diabetes-EA/EGJA association (P for interaction = .04) with a 63% increased risk among participants with regurgitation (OR, 1.63; 95% CI, 1.19-2.22), but not among those without regurgitation (OR, 1.03; 95% CI, 0.74-1.43). No consistent association was found between diabetes and BE. CONCLUSIONS: Diabetes was associated with increased EA and EGJA risk, which was confined to individuals with regurgitation symptoms. Lack of an association between diabetes and BE suggests that diabetes may influence progression of BE to cancer.

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.
Int J Epidemiol ; 48(3): 781-794, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-31243447

RESUMO

BACKGROUND: Evidence linking breast size to breast cancer risk has been inconsistent, and its interpretation is often hampered by confounding factors such as body mass index (BMI). Here, we used linkage disequilibrium score regression and two-sample Mendelian randomization (MR) to examine the genetic associations between BMI, breast size and breast cancer risk. METHODS: Summary-level genotype data from 23andMe, Inc (breast size, n = 33 790), the Breast Cancer Association Consortium (breast cancer risk, n = 228 951) and the Genetic Investigation of ANthropometric Traits (BMI, n = 183 507) were used for our analyses. In assessing causal relationships, four complementary MR techniques [inverse variance weighted (IVW), weighted median, weighted mode and MR-Egger regression] were used to test the robustness of the results. RESULTS: The genetic correlation (rg) estimated between BMI and breast size was high (rg = 0.50, P = 3.89x10-43). All MR methods provided consistent evidence that higher genetically predicted BMI was associated with larger breast size [odds ratio (ORIVW): 2.06 (1.80-2.35), P = 1.38x10-26] and lower overall breast cancer risk [ORIVW: 0.81 (0.74-0.89), P = 9.44x10-6]. No evidence of a relationship between genetically predicted breast size and breast cancer risk was found except when using the weighted median and weighted mode methods, and only with oestrogen receptor (ER)-negative risk. There was no evidence of reverse causality in any of the analyses conducted (P > 0.050). CONCLUSION: Our findings indicate a potential positive causal association between BMI and breast size and a potential negative causal association between BMI and breast cancer risk. We found no clear evidence for a direct relationship between breast size and breast cancer risk.

8.
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
9.
Mol Genet Genomic Med ; 7(6): e707, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31066241

RESUMO

BACKGROUND: Epidemiological studies consistently indicate that alcohol consumption is an independent risk factor for female breast cancer (BC). Although the aldehyde dehydrogenase 2 (ALDH2) polymorphism (rs671: Glu>Lys) has a strong effect on acetaldehyde metabolism, the association of rs671 with BC risk and its interaction with alcohol intake have not been fully elucidated. We conducted a pooled analysis of 14 case-control studies, with individual data on Asian ancestry women participating in the Breast Cancer Association Consortium. METHODS: We included 12,595 invasive BC cases and 12,884 controls for the analysis of rs671 and BC risk, and 2,849 invasive BC cases and 3,680 controls for the analysis of the gene-environment interaction between rs671 and alcohol intake for BC risk. The pooled odds ratios (OR) with 95% confidence intervals (CI) associated with rs671 and its interaction with alcohol intake for BC risk were estimated using logistic regression models. RESULTS: The Lys/Lys genotype of rs671 was associated with increased BC risk (OR = 1.16, 95% CI 1.03-1.30, p = 0.014). According to tumor characteristics, the Lys/Lys genotype was associated with estrogen receptor (ER)-positive BC (OR = 1.19, 95% CI 1.05-1.36, p = 0.008), progesterone receptor (PR)-positive BC (OR = 1.19, 95% CI 1.03-1.36, p = 0.015), and human epidermal growth factor receptor 2 (HER2)-negative BC (OR = 1.25, 95% CI 1.05-1.48, p = 0.012). No evidence of a gene-environment interaction was observed between rs671 and alcohol intake (p = 0.537). CONCLUSION: This study suggests that the Lys/Lys genotype confers susceptibility to BC risk among women of Asian ancestry, particularly for ER-positive, PR-positive, and HER2-negative tumor types.

10.
Epidemiology ; 30(3): 449-457, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30964816

RESUMO

BACKGROUND: Data on breastfeeding and breast cancer risk are sparse and inconsistent for Hispanic women. METHODS: Pooling data for nearly 6,000 parous Hispanic women from four population-based studies conducted between 1995 and 2007 in the United States and Mexico, we examined the association of breastfeeding with risk of breast cancer overall and subtypes defined by estrogen receptor (ER) and progesterone receptor (PR) status, and the joint effects of breastfeeding, parity, and age at first birth. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using logistic regression. RESULTS: Among parous Hispanic women, older age at first birth was associated with increased breast cancer risk, whereas parity was associated with reduced risk. These associations were found for hormone receptor positive (HR+) breast cancer only and limited to premenopausal women. Age at first birth and parity were not associated with risk of ER- and PR- breast cancer. Increasing duration of breastfeeding was associated with decreasing breast cancer risk (≥25 vs. 0 months: OR = 0.73; 95% CI = 0.60, 0.89; Ptrend = 0.03), with no heterogeneity by menopausal status or subtype. At each parity level, breastfeeding further reduced HR+ breast cancer risk. Additionally, breastfeeding attenuated the increase in risk of HR+ breast cancer associated with older age at first birth. CONCLUSIONS: Our findings suggest that breastfeeding is associated with reduced risk of both HR+ and ER- and PR- breast cancer among Hispanic women, as reported for other populations, and may attenuate the increased risk in women with a first pregnancy at older ages.


Assuntos
Aleitamento Materno/etnologia , Neoplasias da Mama/etnologia , Hispano-Americanos/estatística & dados numéricos , Paridade , Receptores Estrogênicos/análise , Receptores de Progesterona/análise , Adulto , Idoso , Aleitamento Materno/estatística & dados numéricos , Feminino , Humanos , México/epidemiologia , Pessoa de Meia-Idade , Gravidez , Fatores de Risco , Estados Unidos/epidemiologia
11.
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.

12.
J Nutr ; 149(4): 619-627, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30926986

RESUMO

BACKGROUND: Consumption of green tea has been associated with reduced risk of breast cancer. Hormonal modulation has been suggested as one of the potential underlying mechanisms; however, it has yet to be fully elucidated in large, long-term human clinical trials. OBJECTIVE: We investigated the effects of decaffeinated green tea extract (GTE) on circulating sex hormones and insulin-like growth factor (IGF) proteins. METHODS: We conducted a placebo-controlled double-blind randomized clinical trial recruiting from 8 clinical centers in Minnesota. Participants were 538 healthy postmenopausal women randomly assigned to the GTE group (463 completed the study; mean age = 60.0 y) and 537 to the placebo group (474 completed; mean age = 59.7 y). Women in the GTE group orally took 4 decaffeinated capsules containing 1315 mg total catechins including 843 mg epigallocatechin-3-gallate daily for 1 y, whereas women in the placebo group took similar capsules containing no tea catechins. Blood sex hormones (estrone, estradiol, androstenedione, testosterone, and sex hormone-binding globulin) and IGF proteins (IGF-1 and IGF binding protein-3) were quantified at baseline and months 6 (for IGF proteins only) and 12, and were assessed as secondary outcomes of the study using a mixed-effect repeated-measures ANOVA model. RESULTS: Women in the GTE group had significantly higher blood total estradiol (16%; P = 0.02) and bioavailable estradiol (21%; P = 0.03) than in the placebo group at month 12. There was a statistically significant interaction between GTE supplementation and duration of treatment on estradiol and bioavailable estradiol (both Ps for interaction = 0.001). The catechol-O-methyltransferase genotype did not influence blood sex hormones before or after GTE supplementation. The circulating concentrations of IGF proteins were comparable between GTE and placebo groups at all 3 time points. CONCLUSION: These results suggest that a 12-mo GTE supplementation significantly increases circulating estradiol concentrations in healthy postmenopausal women. This trial was registered at clinicaltrials.gov as NCT00917735.

13.
Int J Cancer ; 2019 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-30924138

RESUMO

Previous studies using different exposure methods to assess air pollution and breast cancer risk among primarily whites have been inconclusive. Air pollutant exposures of particulate matter and oxides of nitrogen were estimated by kriging (NOx , NO2 , PM10 , PM2.5 ), land use regression (LUR, NOx , NO2 ) and California Line Source Dispersion model (CALINE4, NOx , PM2.5 ) for 57,589 females from the Multiethnic Cohort, residing largely in Los Angeles County from recruitment (1993-1996) through 2010. Cox proportional hazards models were used to examine the associations between time-varying air pollution and breast cancer incidence adjusting for confounding factors. Stratified analyses were conducted by race/ethnicity and distance to major roads. Among all women, breast cancer risk was positively but not significantly associated with NOx (per 50 parts per billion [ppb]) and NO2 (per 20 ppb) determined by kriging and LUR and with PM2.5 and PM10 (per 10 µg/m3 ) determined by kriging. However, among women who lived within 500 m of major roads, significantly increased risks were observed with NOx (hazard ratio [HR] = 1.35, 95% confidence interval [95% CI]: 1.02-1.79), NO2 (HR = 1.44, 95% CI: 1.04-1.99), PM10 (HR = 1.29, 95% CI: 1.07-1.55) and PM2.5 (HR = 1.85, 95% CI: 1.15-2.99) determined by kriging and NOx (HR = 1.21, 95% CI:1.01-1.45) and NO2 (HR = 1.26, 95% CI: 1.00-1.59) determined by LUR. No overall associations were observed with exposures assessed by CALINE4. Subgroup analyses suggested stronger associations of NOx and NO2 among African Americans and Japanese Americans. Further studies of multiethnic populations to confirm the effects of air pollution, particularly near-roadway exposures, on the risk of breast cancer is warranted.

14.
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
15.
Clin Gastroenterol Hepatol ; 17(11): 2227-2235.e1, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30716477

RESUMO

BACKGROUND & AIMS: Epidemiology studies of circulating concentrations of 25 hydroxy vitamin D (25(OH)D) and risk of esophageal adenocarcinoma (EAC) have produced conflicting results. We conducted a Mendelian randomization study to determine the associations between circulating concentrations of 25(OH)D and risks of EAC and its precursor, Barrett's esophagus (BE). METHODS: We conducted a Mendelian randomization study using a 2-sample (summary data) approach. Six single-nucleotide polymorphisms (SNPs; rs3755967, rs10741657, rs12785878, rs10745742, rs8018720, and rs17216707) associated with circulating concentrations of 25(OH)D were used as instrumental variables. We collected data from 6167 patients with BE, 4112 patients with EAC, and 17,159 individuals without BE or EAC (controls) participating in the Barrett's and Esophageal Adenocarcinoma Consortium, as well as studies from Bonn, Germany, and Cambridge and Oxford, United Kingdom. Analyses were performed separately for BE and EAC. RESULTS: Overall, we found no evidence for an association between genetically estimated 25(OH)D concentration and risk of BE or EAC. The odds ratio per 20 nmol/L increase in genetically estimated 25(OH)D concentration for BE risk estimated by combining the individual SNP association using inverse variance weighting was 1.21 (95% CI, 0.77-1.92; P = .41). The odds ratio for EAC risk, estimated by combining the individual SNP association using inverse variance weighting, was 0.68 (95% CI, 0.39-1.19; P = .18). CONCLUSIONS: In a Mendelian randomization study, we found that low genetically estimated 25(OH)D concentrations were not associated with risk of BE or EAC.

16.
Neuro Oncol ; 21(4): 498-507, 2019 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-30615143

RESUMO

BACKGROUND: Meningioma is the most common intracranial tumor in the US and its etiology remains poorly understood. Meningioma has been predominantly studied among white populations. The aim of this study was to evaluate the associations of anthropometric, comorbidity, and hormonal factors with meningioma in an ethnically diverse population. METHODS: A nested case-control analysis was performed within the Multiethnic Cohort (MEC). Meningioma cases were identified via linkage with Medicare and the California Office of Statewide Health Planning and Development Hospital Discharge data and were matched to up to 10 controls. Anthropometric, comorbidities, physical activity level, and hormonal factors at baseline based on questionnaires were evaluated for association with meningioma. RESULTS: A total of 894 cases and 8918 matched controls were included in this study. Increasing body mass index (BMI) (P-trend = 0.041) and weight increases since age 21 (P-trend = 0.0052) were positively associated with meningioma. Hormonal factors including oral contraceptive use (odds ratio [OR]: 1.24; 95% CI: 1.01-1.51) and estrogen hormonal therapy use (per 5 years, OR: 1.07; 95% CI: 1.01-1.15) were associated with meningioma risk. Hypertension was positively associated with meningioma (OR: 1.26; 95% CI: 1.09-1.47), with individuals who reported a history of both hypertension and diabetes showing a stronger association (OR: 1.54; 95% CI: 1.17-2.03). The tests for heterogeneity across race/ethnicity were not statistically significant (P heterogeneity ≥ 0.17); however, the association of BMI with meningioma was mainly observed in Japanese Americans (P-trend = 0.0036) and hypertension in Japanese Americans (OR: 1.63; 95% CI: 1.17-2.27) and Native Hawaiians (OR: 1.86; 95% CI: 1.02-3.40). CONCLUSION: Obesity, hormonal factors, and hypertension were associated with meningioma in an ethnically diverse population.

17.
J Alzheimers Dis ; 67(2): 769-778, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30689589

RESUMO

BACKGROUND: Medicare claims record linkage has been used to identify diagnosed dementia cases in order to estimate dementia prevalence and cost of care. Claims records in the 1990 s and early 2000 s have been found to provide 85% - ∼90% sensitivity and specificity. OBJECTIVE: Considering that dementia awareness has improved over time, we sought to examine sensitivity and specificity of more recent Medicare claims records against a standard criterion, clinical diagnosis of dementia. METHODS: For a sample of patients evaluated at the University of Southern California Alzheimer Disease Research Center (ADRC), we performed database linkage with Medicare claims files for a six-year period, 2007-2012. We used clinical diagnosis at the ADRC as the criterion diagnosis in order to calculate sensitivity and specificity. RESULTS: Medicare claims correctly identified 85% of dementia patients and 77% of individuals with normal cognition. About half of patients clinically diagnosed with mild cognitive impairment had dementia diagnoses in Medicare claims. Misclassified dementia patients (i.e., missed diagnosis by Medicare claims) had more favorable Mini-Mental State Examination and Clinical Dementia Rating scores and were less likely to present behavioral symptoms than correctly-classified dementia patients. CONCLUSIONS: Database linkage to Medicare claims records is an efficient and reasonably accurate tool to identify dementia cases in a population-based cohort. However, possibilities of obtaining biased results due to misclassification of dementia status need to be carefully considered to use Medicare claims diagnosis for etiologic research studies. Additional confirmation of dementia diagnosis may also be considered. A larger study is warranted to confirm our findings.

18.
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.

19.
BMC Cancer ; 18(1): 1072, 2018 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-30400783

RESUMO

BACKGROUND: The contribution of genetic polymorphisms to the large inter-individual variation in mammographic density (MD) changes following starting and stopping use of estrogen and progestin combined therapy (EPT) has not been well-studied. Previous studies have shown that circulating levels of insulin-like growth factors are associated with MD and cross-talk between estrogen signaling and growth factors is necessary for cell proliferation in the breast. We evaluated single nucleotide polymorphisms (SNPs) in growth factor genes in association with MD changes after women stop EPT use. METHODS: We genotyped 191 SNPs in 13 growth factor pathway genes in 284 non-Hispanic white California Teachers Study participants who previously used EPT and collected their mammograms before and after quitting EPT. Percent MD was assessed using a computer-assisted method. Change in percent MD was calculated by subtracting percent MD of an 'off-EPT' mammogram from percent MD of an 'on-EPT' (i.e. baseline) mammogram. We used multivariable linear regression analysis to investigate the association between SNPs and change in percent MD. We calculated P-values corrected for multiple testing within a gene (Padj). RESULTS: Rs1983210 in INHA and rs35539615 in IGFBP1/3 showed the strongest associations. Per minor allele of rs1983210, the absolute change in percent MD after stopping EPT use decreased by 1.80% (a difference in absolute change in percent MD) (Padj= 0.021). For rs35539615, change in percent MD increased by 1.79% per minor allele (Padj= 0.042). However, after applying a Bonferroni correction for the number of genes tested, these associations were no longer statistically significant. CONCLUSIONS: Genetic variation in growth factor pathway genes INHA and IGFBP1/3 may predict longitudinal MD change after women quit EPT. The observed differences in EPT-associated changes in percent MD in association with these genetic polymorphisms are modest but may be clinically significant considering that the magnitude of absolute increase in percent MD reported from large clinical trials of EPT ranged from 3% to 7%.

20.
Br J Cancer ; 118(12): 1639-1647, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29795306

RESUMO

BACKGROUND: Substantial evidence supports an association between use of menopausal hormone therapy and decreased colorectal cancer (CRC) risk, indicating a role of exogenous sex hormones in CRC development. However, findings on endogenous oestrogen exposure and CRC are inconsistent. METHODS: We used a Mendelian randomisation approach to test for a causal effect of age at menarche and age at menopause as surrogates for endogenous oestrogen exposure on CRC risk. Weighted genetic risk scores based on 358 single-nucleotide polymorphisms associated with age at menarche and 51 single-nucleotide polymorphisms associated with age at menopause were used to estimate the association with CRC risk using logistic regression in 12,944 women diagnosed with CRC and 10,741 women without CRC from three consortia. Sensitivity analyses were conducted to address pleiotropy and possible confounding by body mass index. RESULTS: Genetic risk scores for age at menarche (odds ratio per year 0.98, 95% confidence interval: 0.95-1.02) and age at menopause (odds ratio 0.98, 95% confidence interval: 0.94-1.01) were not significantly associated with CRC risk. The sensitivity analyses yielded similar results. CONCLUSIONS: Our study does not support a causal relationship between genetic risk scores for age at menarche and age at menopause and CRC risk.

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