IFNL4-ΔG is associated with prostate cancer among men at increased risk of sexually transmitted infections

Abstract

Sexually transmitted infections can reach the prostate gland where their harmful effects are mediated by innate immunity, including interferons. Humans are polymorphic for the germline dinucleotide variant, rs368234815-TT/ΔG, in the <i>IFNL4</i> gene encoding interferon λ4. Since the <i>IFNL4-</i>ΔG allele has been linked to impaired viral clearance, we hypothesized that potential exposure to sexually transmitted pathogens, as assessed by the number of lifetime sexual partners, may increase prostate cancer risk in an <i>IFNL4-</i>ΔG-dependent manner. Accordingly, we find that men with 10 or more sexual partners and at least one copy of <i>IFNL4-</i>ΔG have a significantly increased risk of prostate cancer while those with the same number of partners but lacking <i>IFNL4-</i>ΔG do not. Moreover, a test for effect modification shows a positive interaction between the number of lifetime partners and <i>IFNL4-</i>ΔG in the development of aggressive prostate cancer. Based on these findings, we conclude that a gene-environment interaction between <i>IFNL4-</i>ΔG and sexual activity may increase the risk of prostate cancer.