학술논문
IFNL4 -ΔG is associated with prostate cancer among men at increased risk of sexually transmitted infections.
Document Type
Academic Journal
Author
Minas TZ; Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.; Tang W; Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.; Smith CJ; Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.; Onabajo OO; Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, MD, USA.; Obajemu A; Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, MD, USA.; Dorsey TH; Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.; Jordan SV; Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.; Obadi OM; Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.; Ryan BM; Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.; Prokunina-Olsson L; Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, MD, USA.; Loffredo CA; Cancer Prevention and Control Program, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA.; Ambs S; Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA. ambss@mail.nih.gov.
Source
Publisher: Nature Publishing Group UK Country of Publication: England NLM ID: 101719179 Publication Model: eCollection Cited Medium: Internet ISSN: 2399-3642 (Electronic) Linking ISSN: 23993642 NLM ISO Abbreviation: Commun Biol Subsets: PubMed not MEDLINE
Subject
Language
English
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.
Competing Interests: Ludmila Prokunina-Olsson receives royalty income for the anti-IFN-λ4 antibody used in this paper. The remaining authors declare no competing interests.
Competing Interests: Ludmila Prokunina-Olsson receives royalty income for the anti-IFN-λ4 antibody used in this paper. The remaining authors declare no competing interests.