Contributions of PARP-1 rs1136410 C>T polymorphism to the development of cancer

Abstract

Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear chromatin-associated enzyme involved in the DNA damage response. SNP rs1136410 C>T, the most studied polymorphism in PARP-1 gene, is highly implicated in the susceptibility of cancer. However, the roles of PARP-1 rs1136410 C>T on cancer risk vary from different studies. We comprehensively screened all qualified publications from several databases, including PubMed, EMBASE, MEDLINE, CNKI and Wanfang. The searching was updated to April 2020. Our meta-analysis included 60 articles with 65 studies, comprised of a total of 23 996 cases with cancer and 33 015 controls. Overall, pooled data showed that the PARP-1 rs1136410 C>T polymorphism was significantly but a border-line associated with an increased risk of overall cancer (CC vs. TT/TC: OR = 1.11, 95% CI = 1.00-1.24; C vs T: OR = 1.07, 95% CI = 1.01-1.14). Subgroup analysis indicated that rs1136410 C allele contributed to high risk among gastric, thyroid, and cervical cancer, but lower risk among brain cancer. Furthermore, increased cancer risk was detected in the subgroups of Asian, controls from population-based design studies, and HWE ≤ 0.05 studies. Sensitivity analysis and Egger's test showed that results of the meta-analysis were fairly stable. The current study indicated that PARP1 rs1136410 C>T polymorphism may have an impact on certain types of cancer susceptibility.

Keywords: PARP1; cancer; meta-analysis; risk; rs1136410 C>T.

FIGURE 1

Forest plot of studies evaluating pooled ORs of cancer risk under the dominant comparison model. Squares represent risk estimates of each study. The horizontal line represents study specific ORs and 95% CIs. The diamonds represent pooled estimates and 95%