Abstract
Numerous epidemiological studies have evaluated the association between polymorphism in the gene encoding x-ray repair cross complementing 1 (XRCC1) protein and the risk of female reproductive system cancer, but results are inconclusive. To gain a comprehensive picture of available evidence, we searched for relevant studies in the PubMed, EMBASE, Scopus, and Chinese National Knowledge Infrastructure databases up to December 17, 2016. A total of 26 case-control studies were picked out. The pooled odds ratio (OR) with its 95% confidence interval (CI) was calculated to estimate the association. Based on data of all study participants, we did not find a positive association of rs25487 or rs1799782 polymorphism with risk of female reproductive cancer risk. Subgroup analysis, however, identified two alleles as being associated with an increased risk of female reproductive system cancer in Asians: the A allele of rs25487 (heterozygous genetic model, OR 1.16, 95%CI 1.00–1.36), and the T allele of rs1799782 (homozygous model, OR 2.30, 95%CI 1.39–3.82; dominant model, OR 1.28, 95%CI 1.10–1.50; recessive model, OR 2.11, 95%CI 1.33–3.34). Moreover, the AA genotype at rs25489 was determined to be a risk factor for cervical cancer etiology (homozygous model, OR 2.91, 95%CI, 1.17–7.26; recessive model, OR 3.16, 95%CI 1.91–5.24). This meta-analysis suggests that no association between rs25487 or rs1799782 gene polymorphism and risk of female reproductive cancer risk was found. These results should be validated in larger studies.
Highlights
Female reproductive system cancer, which includes cervical cancer, endometrial cancer, and ovarian cancer, is a major threat to women’s health
26 case-control studies were included in this study (Table 1): data on rs25487 were reported in 24 studies involving 4,265 cases and 5,495 controls; data on rs1799782 were reported in 15 studies involving 2,672 cases and 3,578 controls; and data on rs25489 were reported in 5 studies with 907 cases and 1,416 controls
x-ray repair cross complementing 1 (XRCC1) is the first protein to participate in the base excision repair (BER) pathway, acting as a scaffold for other DNA repair proteins, such as DNA ligase IIIa, DNA polymerase β and poly (ADP-ribose) polymerase [40]
Summary
Female reproductive system cancer, which includes cervical cancer, endometrial cancer, and ovarian cancer, is a major threat to women’s health. Elucidating the etiology of female reproductive system cancer and identifying at-risk populations may allow more effective early detection and perhaps even prevention. The causes of these cancers remain poorly understood. One possible genetic factor may be polymorphism in the gene encoding x-ray repair cross complementing 1 (XRCC1) protein. While more than 300 XRCC1 SNPs have been described in the dbSNP database, three functional SNPs have been extensively studied, all of which cause amino acid substitutions in the encoded protein: rs25487 [Arg399Gln], rs1799782 [Arg194Trp] and rs25489 [Arg280His]
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