IFNL4-ΔG is associated with prostate cancer among men at increased risk of sexually transmitted infections.
IFNL4-ΔG is associated with prostate cancer among men at increased risk of sexually transmitted infections.
复制标题
DOI：
10.1038/s42003-018-0193-5
复制
发表时间：
2018
影响因子：
5.9
通讯作者：
Ambs S
中科院分区：
文献类型：
--
作者：
Minas TZ;Tang W;Smith CJ;Onabajo OO;Obajemu A;Dorsey TH;Jordan SV;Obadi OM;Ryan BM;Prokunina-Olsson L;Loffredo CA;Ambs S
性传播感染可到达前列腺，在那里它们的有害影响由先天免疫，包括干扰素介导。人类在编码干扰素λ4的IFNL 4基因中的生殖系二核苷酸变体rs368234815-TT/ΔG具有多态性。由于IFNL 4-ΔG等位基因与病毒清除受损有关，因此我们假设潜在的性传播病原体暴露（通过终生性伴侣数量评估）可能以IFNL 4-Δ G依赖性方式增加前列腺癌风险。因此，我们发现，有10个或更多性伴侣且至少有一个IFNL 4-ΔG拷贝的男性患前列腺癌的风险显著增加，而那些有相同数量性伴侣但缺乏IFNL 4-ΔG的男性则没有。此外，效应修正测试显示，在侵袭性前列腺癌的发展中，终身伴侣的数量与IFNL 4-ΔG之间存在积极的相互作用。基于这些发现，我们得出结论，IFNL 4-ΔG和性活动之间的基因-环境相互作用可能会增加前列腺癌的风险。Tsion Zewdu Minas等人发现，携带IFNL 4变体的男性患前列腺癌的风险更高，该变体在非洲裔美国人中更常见，并与病毒清除受损有关。具体来说，这种风险在IFNL 4变异携带者中增加，终生性伴侣更多，这表明与性传播感染清除受损有关
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
登录
查看更多内容
影响因子：
8.8
作者：
Ewings, P;Bowie, C
通讯作者：
Bowie, C
影响因子：
11.4
作者：
Hamming, Ole J.;Terczynska-Dyla, Ewa;Vieyres, Gabrielle;Dijkman, Ronald;Jorgensen, Sanne E.;Akhtar, Hashaam;Siupka, Piotr;Pietschmann, Thomas;Thiel, Volker;Hartmann, Rune
通讯作者：
Hartmann, Rune
影响因子：
5.4
作者：
Dennis, LK;Dawson, DV
通讯作者：
Dawson, DV
影响因子：
6.4
作者：
Jenkins, F. J.;Hayes, R. B.;Goedert, J. J.
通讯作者：
Goedert, J. J.
影响因子：
4.5
作者：
Giles, GG;Severi, G;Hopper, JL
通讯作者：
Hopper, JL