Identification of novel epithelial ovarian cancer loci in women of African ancestry.
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ABSTRACT:
SUBMITTER: Manichaikul A
PROVIDER: S-EPMC7523187 | biostudies-literature | 2020 Jun
REPOSITORIES: biostudies-literature
Publications
Identification of novel epithelial ovarian cancer loci in women of African ancestry.
Manichaikul Ani A Peres Lauren C LC Wang Xin-Qun XQ Barnard Mollie E ME Chyn Deanna D Sheng Xin X Du Zhaohui Z Tyrer Jonathan J Dennis Joseph J Schwartz Ann G AG Cote Michele L ML Peters Edward E Moorman Patricia G PG Bondy Melissa M Barnholtz-Sloan Jill S JS Terry Paul P Alberg Anthony J AJ Bandera Elisa V EV Funkhouser Ellen E Wu Anna H AH Pearce Celeste Leigh CL Pike Malcom M Setiawan Veronica Wendy VW Haiman Christopher A CA Palmer Julie R JR LeMarchand Loic L Wilkens Lynne R LR Berchuck Andrew A Doherty Jennifer A JA Modugno Francesmary F Ness Roberta R Moysich Kirsten K Karlan Beth Y BY Whittemore Alice S AS McGuire Valerie V Sieh Weiva W Lawrenson Kate K Gayther Simon S Sellers Thomas A TA Pharoah Paul P Schildkraut Joellen M JM
International journal of cancer 20191008 11
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<sup>-6</sup> ), including rs4525119 (intronic to AKR1C3), rs7643459 (intronic to LOC101927394), rs ...[more]
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| S-EPMC5448553 | biostudies-literature
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| S-EPMC3697898 | biostudies-literature
Project description:Background: Triple negative epithelial ovarian cancer (TNEOC) refers to ovarian carcinomas that do not express estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor- type 2 (HER-2/neu). The aim of this study is to determine the pattern of triple negative epithelial ovarian cancer in indigenous African women. Methods: We performed a retrospective review of ER, PR and HER-2/neu expression in 90 Nigerian patients with histologically diagnosed epithelial ovarian cancer. Lack of expression of ER, PR and HER2/neu antigens was used to determine carcinomas that are among the TNEOC. We also compared the clinicopathological parameters (age, International Federation of Gynaecology and Obstetrics (FIGO) stage, grade and histological subtype) in patients with TNEOC and non- TNEOC . Results: Thirty-eight (42.2%) of the 90 tumours diagnosed as EOC were negative for ER, PR and HER2/neu expression. There was no significant association between TNEOC with other parameters such as age, FIGO stage and histological grade. Sixteen (66.7%) of the 24 mucinous carcinomas were triple negative, while only 21 (33.3%) of the 63 serous carcinomas were triple-negative and one (50%) of the two endometrioid carcinomas was triple negative. There was a significant association between triple-negative tumours and histological subtypes of EOC (p = 0.034). Conclusions: A subtype of epithelial ovarian cancer that is negative for ER, PR and HER-2/neu has been discovered in indigenous African women. TNEOC expression is high and is comparable to the triple negative breast cancer subtype seen in people of African ancestry. Future study of TNEOC in a large sample size should be considered.
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Project description:Genome-wide association studies (GWAS) have identified 12 epithelial ovarian cancer (EOC) susceptibility alleles. The pattern of association at these loci is consistent in BRCA1 and BRCA2 mutation carriers who are at high risk of EOC. After imputation to 1000 Genomes Project data, we assessed associations of 11 million genetic variants with EOC risk from 15,437 cases unselected for family history and 30,845 controls and from 15,252 BRCA1 mutation carriers and 8,211 BRCA2 mutation carriers (3,096 with ovarian cancer), and we combined the results in a meta-analysis. This new study design yielded increased statistical power, leading to the discovery of six new EOC susceptibility loci. Variants at 1p36 (nearest gene, WNT4), 4q26 (SYNPO2), 9q34.2 (ABO) and 17q11.2 (ATAD5) were associated with EOC risk, and at 1p34.3 (RSPO1) and 6p22.1 (GPX6) variants were specifically associated with the serous EOC subtype, all with P < 5 × 10(-8). Incorporating these variants into risk assessment tools will improve clinical risk predictions for BRCA1 and BRCA2 mutation carriers.
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Project description:Chronic inflammation has been implicated in the development of epithelial ovarian cancer (EOC); yet the contribution of inflammatory foods and nutrients to EOC risk has been understudied. We investigated the association between the dietary inflammatory index (DII), a novel literature-derived tool to assess the inflammatory potential of one's diet, and EOC risk in African American (AA) women in the African American Cancer Epidemiology Study, the largest population-based case-control study of EOC in AA women to date. The energy-adjusted DII (E-DII) was computed per 1,000 kilocalories from dietary intake data collected through a food frequency questionnaire, which measured usual dietary intake in the year prior to diagnosis for cases or interview for controls. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated using multivariable logistic regression for the association between the E-DII and EOC risk. 493 cases and 662 controls were included in the analyses. We observed a 10% increase in EOC risk per a one-unit change in the E-DII (OR = 1.10, 95% CI = 1.03-1.17). Similarly, women consuming the most pro-inflammatory diet had a statistically significant increased EOC risk in comparison to the most anti-inflammatory diet (ORQuartile4/Quartile1 = 1.72; 95% CI = 1.18-2.51). We also observed effect modification by age (p < 0.05), where a strong, significant association between the E-DII and EOC risk was observed among women older than 60 years, but no association was observed in women aged 60 years or younger. Our findings suggest that a more pro-inflammatory diet was associated with an increased EOC risk, especially among women older than 60 years.
| S-EPMC5159198 | biostudies-literature
Project description:PurposeAlthough 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.MethodsWe harmonized risk factors and prognostic characteristics from eight U.S.Studiesthe 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).ResultsDeterminants 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.ConclusionOCWAA 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.
| S-EPMC7325484 | biostudies-literature
Project description:To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC.
| S-EPMC5612337 | biostudies-literature