Following adjustment for surrogates of long-term estrogen exposure, we would predict an increase in BrCa risk estimates for the TLR3 and IRAK4 loci when compared to unadjusted models, based on the observation that long-term estrogen exposure enhances the production of inflammatory mediators in response to TLR4 (and downstream IRAK4) activation. The gene discussed is TLR4; the disease is invasive breast carcinoma.