9q31.2-rs865686 as a susceptibility locus for estrogen receptor-positive breast cancer: evidence from the Breast Cancer Association Consortium
Cancer Epidemiology, Biomarkers & Prevention, 08/10/2012
Warren S et al. – This study is the first to demonstrate that rs865686 is a susceptibility marker for ER+ breast cancer. Impact: The findings further support the view that genetic susceptibility varies according to tumor subtype.
Methods- To further investigate the rs865686-breast cancer association, we conducted a replication study within the Breast Cancer Association Consortium, which comprises 37 case-control studies (48394 cases, 50836 controls).
- This replication study provides additional strong evidence of an inverse association between rs865686 and breast cancer risk (study-adjusted per G-allele odds ratio (OR) 0.90, 95% confidence interval (CI) 0.88, 0.91, P=2.01x10<-29) among women of European ancestry.
- There were ethnic differences in the estimated minor (G) allele frequency among controls (0.09, 0.30 and 0.38 amongst, respectively, Asians, Eastern Europeans and other Europeans; P for heterogeneity (Phet)=1.3x10-143), but no evidence of ethnic differences in per allele OR (Phet=0.43).
- rs865686 was associated with estrogen receptor-positive (ER+) disease (per G-allele OR 0.89, 95% CI 0.86, 0.91, P=3.13x10-22) but less strongly, if at all, with ER-negative (ER-) disease (OR 0.98, 95% CI 0.94, 1.02, P=0.26) (Phet=1.16x10-6), with no evidence of independent heterogeneity by progesterone receptor or human epidermal growth factor receptor-2 status.
- The strength of the breast cancer association decreased with increasing age at diagnosis, with case-only analysis showing a trend in the number of copies of the G allele with increasing age at diagnosis (P for linear trend=0.0095), but only among women with ER+ tumors.
