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TEX15 : A DNA repair gene associated with prostate cancer risk in Han Chinese
Author(s) -
Lin Xiaoling,
Chen Zhongzhong,
Gao Peng,
Gao Zhimei,
Chen Haitao,
Qi Jun,
Liu Fang,
Ye Dingwei,
Jiang Haowen,
Na Rong,
Yu Hongjie,
Shi Rong,
Lu Daru,
Zheng Siqun Lilly,
Mo Zengnan,
Sun Yinghao,
Ding Qiang,
Xu Jianfeng
Publication year - 2017
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.23387
Subject(s) - prostate cancer , medicine , dna repair , prostate , oncology , gene , gynecology , cancer , cancer research , genetics , biology
Background Both common and rare genetic variants may contribute to risk of developing prostate cancer. Genome‐wide association studies (GWASs) have identified ∼100 independent, common variants associated with prostate cancer risk. However, little is known about the association of rare variants (minor allele frequency [MAF] <1%) in the genome with prostate cancer risk. Methods A two‐stage study was used to test the association of rare, deleterious coding variants, annotated using predictive algorithms, with prostate cancer risk in Chinese men. Predicted rare, deleterious coding variants in the Illumina HumanExome‐12 v1.1 beadchip were first evaluated in 1343 prostate cancer patients and 1008 controls. Significant variants were then validated in an additional 1816 prostate cancer patients and 1549 controls. Results In the discovery stage, 14 predicted rare, deleterious coding variants were significantly associated with prostate cancer risk ( P < 0.01). In the confirmation stage, Q1631H in TEX15 (rs142485241), a DNA repair gene, was significantly associated with prostate cancer risk ( P = 0.0069). The estimated odds ratio (OR) of the variant in the combined analysis was 3.24 (95% Confidence Interval 1.85‐6.06), P = 8.81 × 10 −5 . Additionally, rs28756990 (V741F) at MLH3 ( P = 0.06) and rs2961144 (I126V) at OR2A5 ( P = 0.065) were marginally associated with prostate cancer risk in the replication stage. Conclusions Our study provided preliminary evidence that the rare variant Q1631H in DNA repair gene TEX15 is associated with prostate cancer risk. This finding complements known common prostate cancer risk‐associated variants and suggests the possible role of DNA repair genes in prostate cancer development.