scholarly journals Racial differences in population attributable risk for epithelial ovarian cancer in the OCWAA Consortium

Author(s):  
Lauren C Peres ◽  
Traci N Bethea ◽  
Tareq F Camacho ◽  
Elisa V Bandera ◽  
Alicia Beeghly-Fadiel ◽  
...  

Abstract Background The causes of racial disparities in epithelial ovarian cancer (EOC) incidence remain unclear. Differences in the prevalence of ovarian cancer risk factors may explain disparities in EOC incidence among African American (AA) and White women. Methods We used data from four case-control studies and three case-control studies nested within prospective cohorts in the Ovarian Cancer in Women of African Ancestry Consortium to estimate race-specific associations of ten known or suspected EOC risk factors using logistic regression. Using the Bruzzi method, race-specific population attributable risks (PAR) were estimated for each risk factor individually and collectively, including groupings of exposures (reproductive factors and modifiable factors). All statistical tests were two-sided. Results Among 3,244 White EOC cases and 9,638 controls and 1,052 AA EOC cases and 2,410 controls, AA women had a statistically significantly higher PAR (false discovery rate (FDR) P < .001) for first-degree family history of breast cancer (PAR = 10.1%, 95% CI = 6.5% to 13.7%) compared to White women (PAR = 2.6%, 95% CI = 0.8% to 4.4%). After multiple test correction, AA women had a higher PAR than White women when evaluating all risk factors collectively (PAR = 61.6%, 95% CI = 48.6% to 71.3% vs. PAR = 43.0%, 95% CI = 32.8% to 51.4%, respectively; FDR P = .06) and for modifiable exposures, including BMI, oral contraceptives, aspirin, and body powder (PAR = 36.0%, 95% CI = 21.0% to 48.8% vs. PAR = 13.8%, 95% CI = 4.5% to 21.8%, respectively; FDR P = .04). Conclusions Collectively, the selected risk factors accounted for slightly more of the risk among AA than White women, and interventions to reduce EOC incidence that are focused on multiple modifiable risk factors may be slightly more beneficial to AA women than White women at risk for EOC.

2016 ◽  
Vol 184 (8) ◽  
pp. 555-569 ◽  
Author(s):  
Merlise A. Clyde ◽  
Rachel Palmieri Weber ◽  
Edwin S. Iversen ◽  
Elizabeth M. Poole ◽  
Jennifer A. Doherty ◽  
...  

PLoS Medicine ◽  
2019 ◽  
Vol 16 (8) ◽  
pp. e1002893 ◽  
Author(s):  
James Yarmolinsky ◽  
Caroline L. Relton ◽  
Artitaya Lophatananon ◽  
Kenneth Muir ◽  
Usha Menon ◽  
...  

2016 ◽  
Vol 140 (2) ◽  
pp. 277-284 ◽  
Author(s):  
Linda S. Cook ◽  
Andy C.Y. Leung ◽  
Kenneth Swenerton ◽  
Richard P. Gallagher ◽  
Anthony Magliocco ◽  
...  

2018 ◽  
Author(s):  
James Yarmolinsky ◽  
Caroline L Relton ◽  
Artitaya Lophatananon ◽  
Kenneth Muir ◽  
Usha Menon ◽  
...  

AbstractBackgroundVarious modifiable risk factors have been associated with epithelial ovarian cancer risk in observational epidemiological studies. However, the causal nature of the risk factors reported, and thus their suitability as effective intervention targets, is unclear given the susceptibility of conventional observational designs to residual confounding and reverse causation. Mendelian randomization uses genetic variants as proxies for modifiable risk factors to strengthen causal inference in observational studies. We used Mendelian randomization to evaluate the causal role of 13 previously reported risk factors (reproductive, anthropometric, clinical, lifestyle, and molecular factors) in overall and histotype-specific epithelial ovarian cancer in up to 25,509 case subjects and 40,941 controls in the Ovarian Cancer Association Consortium.Methods and FindingsGenetic instruments to proxy 13 risk factors were constructed by identifying single nucleotide polymorphisms (SNPs) robustly (P<5×10−8) and independently associated with each respective risk factor in previously reported genome-wide association studies. SNPs were combined into multi-allelic inverse-variance weighted fixed or random-effects models to generate causal estimates. Three complementary sensitivity analyses were performed to examine violations of Mendelian randomization assumptions: MR-Egger regression and weighted median and mode estimators. A Bonferroni-corrected P-value threshold was used to establish “strong evidence” (P<0.0038) and “suggestive evidence” (0.0038<P<0.05) for associations.In Mendelian randomization analyses, there was strong or suggestive evidence that 9 of 13 risk factors had a causal effect on overall or histotype-specific epithelial ovarian cancer. There was strong evidence that genetic liability to endometriosis increased risk of epithelial ovarian cancer (OR per log odds higher liability:1.27, 95% CI: 1.16-1.40; P=6.94×10−7) and suggestive evidence that lifetime smoking exposure increased risk of epithelial ovarian cancer (OR per unit increase in smoking score:1.36, 95% CI: 1.04-1.78; P=0.02). In histotype-stratified analyses, the strongest associations found were between: height and clear cell carcinoma (OR per SD increase:1.36, 95% CI: 1.15-1.61; P=0.0003); age at natural menopause and endometrioid carcinoma (OR per year later onset:1.09, 95% CI: 1.02-1.16; P=0.007); and genetic liability to polycystic ovary syndrome and endometrioid carcinoma (OR per log odds higher liability:0.74, 95% CI:0.62-0.90; P=0.002). There was little evidence for an effect of genetic liability to type 2 diabetes, parity, or circulating levels of 25-hydroxyvitamin D and sex hormone-binding globulin on ovarian cancer or its subtypes. The primary limitations of this analysis include: modest statistical power for analyses of risk factors in relation to some less common ovarian cancer histotypes (low grade serous, mucinous, and clear cell carcinomas), the inability to directly examine the causal effects of some ovarian cancer risk factors that did not have robust genetic variants available to serve as proxies (e.g., oral contraceptives, hormone replacement therapy), and the assumption of linear relationships between risk factors and ovarian cancer risk.ConclusionsOur comprehensive examination of possible etiological drivers of ovarian carcinogenesis using germline genetic variants to proxy risk factors supports a causal role for few of these factors in epithelial ovarian cancer and suggests distinct etiologies across histotypes. The identification of novel modifiable risk factors remains an important priority for the control of epithelial ovarian cancer.


2013 ◽  
Vol 109 (3) ◽  
pp. 769-776 ◽  
Author(s):  
C Bodelon ◽  
N Wentzensen ◽  
S J Schonfeld ◽  
K Visvanathan ◽  
P Hartge ◽  
...  

2005 ◽  
Vol 16 (8) ◽  
pp. 955-963 ◽  
Author(s):  
Cathrine Hoyo ◽  
Andrew Berchuck ◽  
Susan Halabi ◽  
Rex C. Bentley ◽  
Patricia Moorman ◽  
...  

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