Human herpesvirus 8 infection is associated with prostate cancer among IFNL4-ΔG carriers

Background The dinucleotide germline variant, rs368234815-Delta G, in the IFNL4 gene (IFNL4-Delta G) has been associated with prostate cancer among men at increased risk of sexually transmitted infections and reported to impair viral clearance. Human herpesvirus 8 (HHV-8) seropositivity has been associated with prostate cancer in Tobago. Methods We examined whether the association of HHV-8 with prostate cancer is IFNL4-Delta G-dependent among 728 IFNL4-Delta G-genotyped cases and 813 genotyped population-based controls from the NCI-Maryland Prostate Cancer Case-Control study. Associations between HHV-8 and prostate cancer were assessed in multivariable unconditional logistic regression models. We calculated adjusted odds ratios (OR) and stratified the analysis into men harboring the IFNL4-Delta G-variant and non-carriers (Delta G/Delta G or Delta G/TT vs. TT/TT). Results HHV-8 seropositivity was higher in cases than controls (11% vs. 6%) and this association was restricted to carriers of the Delta G allele (OR 2.19: 95% CI:1.38-3.48) in both African American (OR 1.96; 95% CI:1.08-3.56) and European American men (OR 2.59; 95% CI:1.20-5.56). Conclusions HHV-8 seropositivity is associated with increased odds of prostate cancer in men harboring the IFNL4 rs368234815-Delta G variant. This study describes HHV-8 infection as a candidate prostate cancer risk factor in men with the IFNL4-Delta G genotype and supports the hypothesis that IFNL4-Delta G is a susceptibility factor that contributes to prostate cancer.

Automated summary

This study found that HHV-8 infection is associated with an increased risk of prostate cancer in men harboring the IFNL4-Delta G variant, supporting the hypothesis that IFNL4-Delta G is a susceptibility factor for prostate cancer.