Minas Tsion Zewdu, Tang Wei, Smith Cheryl J, Onabajo Olusegun O, Obajemu Adeola, Dorsey Tiffany H, Jordan Symone V, Obadi Obadi M, Ryan Bríd M, Prokunina-Olsson Ludmila, Loffredo Christopher A, Ambs Stefan
Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.
Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, MD, USA.
Commun Biol. 2018 Nov 14;1:191. doi: 10.1038/s42003-018-0193-5. eCollection 2018.
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 gene encoding interferon λ4. Since the 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 ΔG-dependent manner. Accordingly, we find that men with 10 or more sexual partners and at least one copy of ΔG have a significantly increased risk of prostate cancer while those with the same number of partners but lacking ΔG do not. Moreover, a test for effect modification shows a positive interaction between the number of lifetime partners and ΔG in the development of aggressive prostate cancer. Based on these findings, we conclude that a gene-environment interaction between ΔG and sexual activity may increase the risk of prostate cancer.
性传播感染可累及前列腺，其有害影响由包括干扰素在内的先天免疫介导。人类在编码干扰素λ4的基因中，种系二核苷酸变体rs368234815 - TT/ΔG存在多态性。由于ΔG等位基因与病毒清除受损有关，我们推测，通过终身性伴侣数量评估的潜在性传播病原体暴露，可能以依赖ΔG的方式增加前列腺癌风险。相应地，我们发现有10个或更多性伴侣且至少有一份ΔG拷贝的男性患前列腺癌的风险显著增加，而有相同数量性伴侣但缺乏ΔG的男性则没有。此外，效应修饰检验显示，终身性伴侣数量与ΔG在侵袭性前列腺癌发生过程中存在正向相互作用。基于这些发现，我们得出结论，ΔG与性活动之间的基因 - 环境相互作用可能增加前列腺癌风险。
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