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IFNL4-?G 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/?G, in the IFNL4 gene encoding interferon ?4. Since the IFNL4-?G 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-?G-dependent manner. Accordingly, we find that men with 10 or more sexual partners and at least one copy of IFNL4-?G have a significantly increased risk of prostate cancer while those with the same number of partners but lacking IFNL4-?G do not. Moreover, a test for effect modification shows a positive interaction between the number of lifetime partners and IFNL4-?G in the development of aggressive prostate cancer. Based on these findings, we conclude that a gene-environment interaction between IFNL4-?G and sexual activity may increase the risk of prostate cancer.

SUBMITTER: Minas TZ

PROVIDER: S-EPMC6235841 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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

Minas Tsion Zewdu TZ Tang Wei W Smith Cheryl J CJ Onabajo Olusegun O OO Obajemu Adeola A Dorsey Tiffany H TH Jordan Symone V SV Obadi Obadi M OM Ryan Bríd M BM Prokunina-Olsson Ludmila L Loffredo Christopher A CA Ambs Stefan S

Communications biology 20181114

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 pros ...[more]

PMID: 30456312

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Project description:ObjectiveTo determine the effectiveness of a brief cognitive behavioural intervention in reducing the incidence of sexually transmitted infections among gay men.DesignRandomised controlled trial with 12 months' follow up.SettingSexual health clinic in London.Participants343 gay men with an acute sexually transmitted infection or who reported having had unprotected anal intercourse in the past year.Main outcome measuresNumber of new sexually transmitted infections diagnosed during follow up and self reported incidence of unprotected anal intercourse.Results72% (361/499) of men invited to enter the study did so. 90% (308/343) of participants returned at least one follow up questionnaire or re-attended the clinic and requested a check up for sexually transmitted infections during follow up. At baseline, 37% (63/172) of the intervention group and 30% (50/166) of the control group reported having had unprotected anal intercourse in the past month. At 12 months, the proportions were 27% (31/114) and 32% ( 39/124) respectively (P=0.56). However, 31% (38/123) of the intervention group and 21% (35/168) of controls had had at least one new infection diagnosed at the clinic (adjusted odds ratio 1.66, 95% confidence interval 1.00 to 2.74). Considering only men who requested a check up for sexually transmitted infections, the proportion diagnosed with a new infection was 58% (53/91) for men in the intervention group and 43% (35/81) for men in the control group (adjusted odds ratio 1.84, 0.99 to 3.40). Using a regional database that includes information from 23 sexual health clinics in London, we determined that few participants had attended other sexual health clinics.ConclusionsThis behavioural intervention was acceptable and feasible to deliver, but it did not reduce the risk of acquiring a new sexually transmitted infection among these gay men at high risk. Even carefully designed interventions should not be assumed to bring benefit. It is important to evaluate their effects in randomised trials with objective clinical end points.

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

Publications

<i>IFNL4</i>-ΔG is associated with prostate cancer among men at increased risk of sexually transmitted infections.

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