Combined and interactive effects of environmental and GWAS-identified risk factors in ovarian cancer Ovarian Cancer and Us OVARIAN CANCER and US Ovarian Cancer and Us

Blog Archives: Nov 2004 - present

#ovariancancers



Special items: Ovarian Cancer and Us blog best viewed in Firefox

Search This Blog

Monday, March 11, 2013

Combined and interactive effects of environmental and GWAS-identified risk factors in ovarian cancer



Abstract

Background:  
There are several well-established environmental risk factors for ovarian cancer, and recent genome-wide association studies have also identified six variants that influence disease risk. However, the interplay between such risk factors and susceptibility loci has not been studied. 
Methods: 
Data from 14 ovarian cancer case-control studies were pooled, and stratified analyses by each environmental risk factor with tests for heterogeneity were conducted to determine the presence of interactions for all histological subtypes. A genetic "risk score" was created to consider the effects of all six variants simultaneously. A multivariate model was fit to examine the association between all environmental risk factors and genetic risk score on ovarian cancer risk.
Results: 
Among 7,374 controls and 5,566 cases, there was no statistical evidence of interaction between the six SNPs or genetic risk score and the environmental risk factors on ovarian cancer risk. In a main effects model, women in the highest genetic risk score quartile had a 65% increased risk of ovarian cancer compared to women in the lowest (95% CI 1.48-1.84). Analyses by histological subtype yielded risk differences across subtype for endometriosis (phet<0.001), parity (phet<0.01), and tubal ligation (phet=0.041). 
Conclusions: 
The lack of interactions suggests that a multiplicative model is the best fit for these data. Under such a model, we provide a robust estimate of each risk factor's effect, which sets the stage for absolute risk prediction modeling that considers both environmental and genetic risk factors. Further research into the observed differences in risk across histological subtype is warranted.

0 comments :

Post a Comment

Your comments?

Note: Only a member of this blog may post a comment.