Arg399Gln substitution in XRCC1 as a prognostic and predictive biomarker for prostate cancer: Evidence from 8662 subjects and a structural analysis

• Published in: The journal of gene medicine Vol. 20; no. 10-11; pp. e3053 - n/a
• Main Authors: Noureddini, Mahdi, Mobasseri, Narges, Karimian, Mohammad, Behjati, Mohaddeseh, Nikzad, Hossein
• Format: Journal Article
• Language: English
• Published: England Wiley Periodicals Inc 01.10.2018
• Subjects: Bioinformatics; Biomarkers; Data processing; Gene polymorphism; Gene therapy; Genotyping; in silico analysis; Meta-analysis; Minority & ethnic groups; Polymerase chain reaction; Polymorphism; Prostate cancer; Protein structure; Restriction fragment length polymorphism; Statistical analysis; Structure-function relationships; XRCC1 gene; XRCC1 protein; in silico analysis; meta-analysis; prostate cancer; XRCC1 gene
• ISSN: 1099-498X; 1521-2254; 1521-2254
• DOI: 10.1002/jgm.3053

Background The Arg399Gln polymorphism in the X‐ray repair cross‐complementing group 1 gene (XRCC1) may alter the risk of prostate cancer (PCa). The present study aimed to investigate the association of the XRCC1‐Arg399Gln polymorphism with PCa risk in an Iranian population, as followed by a meta‐analysis and an in silico analysis. Methods In a case–control study, 360 subjects were included (180 men with PCa and 180 healthy controls). XRCC1‐Arg399Gln genotyping was performed using the polymerase chain reaction‐restriction fragment length polymorphism method. In the meta‐analysis, 14 eligible studies were included to which our case–control data were added to estimate the pooled odds ratios. Some bioinformatics tools were employed to evaluate the effects of Arg399Gln substitution on molecular aspects of the XRCC1 protein. Results Our case–control study revealed a significant association between the XRCC1‐Arg399Gln polymorphism and PCa risk. The data from overall meta‐analysis showed significant associations between the mentioned polymorphism and PCa risk in allelic and recessive genetic models. In addition, we observed statistically significant associations in stratified analyses by ethnicity, sample size and source of controls. Our in silico analysis showed that Arg399Gln substitution could be damaging with respect to the function and structure of the XRCC1 protein. Conclusions Based on these results, the XRCC1‐Arg399Gln polymorphism might be a risk factor for PCa and it could be considered as a prognostic and predictive biomarker for susceptible men.