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 IFNL4 gene encoding interferon λ4. Since the IFNL4-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 IFNL4-ΔG-dependent manner. Accordingly, we find that men with 10 or more sexual partners and at least one copy of IFNL4-ΔG have a significantly increased risk of prostate cancer while those with the same number of partners but lacking IFNL4-ΔG do not. Moreover, a test for effect modification shows a positive interaction between the number of lifetime partners and IFNL4-ΔG in the development of aggressive prostate cancer. Based on these findings, we conclude that a gene–environment interaction between IFNL4-ΔG and sexual activity may increase the risk of prostate cancer.

Tsion Zewdu Minas et al. find that men carrying an IFNL4 variant that is more common in African Americans and is associated with impaired viral clearance have a higher risk of prostate cancer. Specifically, this risk is increased in IFNL4 variant carriers with more lifetime sexual partners, suggesting a link to impaired clearance of sexually transmitted infections

Details

Title
IFNL4-ΔG is associated with prostate cancer among men at increased risk of sexually transmitted infections
Author
Zewdu, Minas Tsion 1 ; Tang, Wei 1 ; Smith, Cheryl J 1 ; Onabajo, Olusegun O 2   VIAFID ORCID Logo  ; Adeola, Obajemu 2 ; Dorsey, Tiffany H 1 ; Jordan Symone V 1 ; Obadi, Obadi M 1 ; Ryan, Bríd M 1   VIAFID ORCID Logo  ; Prokunina-Olsson Ludmila 2   VIAFID ORCID Logo  ; Loffredo, Christopher A 3 ; Ambs, Stefan 1   VIAFID ORCID Logo 

1  National Institutes of Health (NIH), Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute (NCI), Bethesda, USA (GRID:grid.94365.3d) (ISNI:0000 0001 2297 5165) 
2  Division of Cancer Epidemiology and Genetics, NCI, NIH, Laboratory of Translational Genomics, Bethesda, USA (GRID:grid.420086.8) (ISNI:0000 0001 2237 2479) 
3  Georgetown University Medical Center, Cancer Prevention and Control Program, Lombardi Comprehensive Cancer Center, Washington, USA (GRID:grid.411667.3) (ISNI:0000 0001 2186 0438) 
Publication year
2018
Publication date
2018
Publisher
Nature Publishing Group
e-ISSN
23993642
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s42003-018-0193-5
ProQuest document ID
2389701180
Copyright
© This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.