4.6 Article

The Association of Polymorphisms in Base Excision Repair Genes with Ovarian Cancer Susceptibility in Chinese Women: A Two-Center Case-Control Study

Journal

JOURNAL OF CANCER
Volume 12, Issue 1, Pages 264-269

Publisher

IVYSPRING INT PUBL
DOI: 10.7150/jca.49925

Keywords

BER; DNA repair; ovarian cancer; susceptibility; polymorphism

Categories

Funding

  1. Lin He's New Medicine and Clinical Translation Academician Workstation Research Fund [17331204]
  2. Zhejiang Provincial Medical and Health Science and Technology plan [2018ZD009]
  3. Major Science and Technology Special Project of Wenzhou Science and Technology Bureau [ZY2020009]
  4. Le Fund [KH-2020-LJJ-030]

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The study revealed that specific polymorphisms in the PARPI, hOGGI, and LIG3 genes may impact the risk of ovarian cancer, with certain variants of PARPI and hOGGI decreasing the risk, while a variant of LIG3 increasing the risk of developing ovarian cancer. Further research with larger and diverse populations is needed to confirm these findings.
Base excision repair (BER) acts upon the most important mechanism of the DNA repair system, protecting DNA stability and integrity from the mutagenic and cytotoxic effects. Multiple researches have indicated that single-nucleotide polymorphisms (SNPs) in the BER-related gene may be associated with the susceptibility of ovarian cancer. However, the results are controversial. In this two-center case-control study, 19 potentially functional SNPs in six BER-related genes (hOGGI , APEI , PARPI, FENI , LIG3 and XRCCI) was genotyped in 196 ovarian cancer cases and 272 cancer-free controls. And, their associations with ovarian cancer risk were assessed by unconditional logistic regression analyses. We found that PARPI rs8679 and hOGGI rs293795 polymorphisms were associated with a decreased risk of ovarian cancer under dominant model (adjusted OR=0.39, 95% CI=0.17-0.90, P=0.026; and adjusted OR=0.36, 95% CI=0.13-0.99, P=0.049, respectively). Stratification analysis demonstrated that this association was more pronounced in the subgroups of lower BMI and patients with early menarche and serous carcinoma. Moreover, LIG3 rs4796030 AA/AC variant genotypes performed an increased risk of ovarian cancer under recessive model (adjusted OR=1.54, 95% CI=1.01-2.35, P=0.046), especially in the subgroups of higher BMI, early clinic stage and the carcinoma at the left. These results suggested that PARPI, hOGGI and LIG3 polymorphisms might impact on the risk of ovarian cancer. However, more researches with larger and different ethnic populations are warranted to support our findings.

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