Association of single nucleotide polymorphisms of DNA repair genes in NER pathway and susceptibility to pancreatic cancer
INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY
Authors: Zhao, Fuli; Shang, Yuhong; Zeng, Chen; Gao, Dongdong; Li, Ke
Abstract
In our study, we conducted a case-control study to investigate the association of ERCC1, ERCC2, ERCC3, ERCC4, ERCC5, XPA, XPC and DDB2 gene polymorphisms in the risk of pancreatic cancer. Between May 2012 and May 2014, a total of 246 patients with who were newly diagnosed with histopathologically confirmed primary pancreatic cancer and 246 controls were selected into our study. Genotyping of ERCC1 rs3212986 and rs11615, ERCC2 rs13181, ERCC3 rs4150441, ERCC4 rs6498486, ERCC5 rs873601, XPA rs2808668, XPC rs2228000, XPC rs2228001 and DDB2 rs2029298 were analyzed using polymerase chain reaction (PCR) coupled with restriction fragment length polymorphism (RFLP). By conditional logistic regression analysis, individuals carrying with TT genotype of ERCC1 rs3212986 and GG genotype of ERCC2 rs13181 were associated with increased risk of pancreatic cancer when compared with wide-type genotype, and the adjusted ORs (95% CI) were 2.40 (1.29-4.52) and 2.27 (1.26-4.15), respectively. We found that individuals carrying with GT+TT genotype of ERCC1 rs3212986 and TG+GG genotype of ERCC2 rs1318 gene polymorphisms were correlated with higher risk of pancreatic cancer in smokers when compared with non-smokers, and the adjusted ORs (95% CI) were 1.89 (1.05-3.40) and 1.88 (1.06-3.34), respectively. In conclusion, our study suggests that ERCC1 rs3212986 and ERCC2 rs1318 gene polymorphisms contribute to the development of pancreatic cancer, especially in smokers.
Association between ERCC1 and XPA expression and polymorphisms and the response to cisplatin in testicular germ cell tumours
BRITISH JOURNAL OF CANCER
Authors: Mendoza, J.; Martinez, J.; Hernandez, C.; Perez-Montiel, D.; Castro, C.; Fabian-Morales, E.; Santibanez, M.; Gonzalez-Barrios, R.; Diaz-Chavez, J.; Andonegui, M. A.; Reynoso, N.; Onate, L. F.; Jimenez, M. A.; Nunez, M.; Dyer, R.; Herrera, L. A.
Abstract
Background: Cisplatin cures over 80% of testicular germ cell tumours (TGCTs), and nucleotide-excision repair (NER) modifies the sensitivity to cisplatin. We explored the association between NER proteins and their polymorphisms with cisplatin sensitivity (CPS) and overall survival (OS) of patients with non-seminomatous (ns)-TGCTs. Methods: The expression of ERCC1 and XPA and the presence of gamma H2AX were evaluated in cancer cell lines and in fresh ns-TGCTs. The ERCC1 protein was also determined in ns-TGCTs. The differences between CPS and non-CPS cell lines and patients were analysed by Student's t- or chi(2)-tests. The differences in OS were analysed using the log-rank test, and the hazard ratios (HRs) were calculated using the Cox model. Results: High ERCC1 expression was observed in the non-CPS cells, and both ERCC1 and gamma H2AX expressions were augmented after cisplatin treatment. Increased ERCC1 expression was also identified in non-CPS patients. Neither polymorphism was associated with either CPS or OS. The presence of ERCC1 was associated with non-CPS (P = 0.05) and adjusted in the prognosis groups. The HR in ERCC1-negative and non-CPS patients was > 14.43, and in ERCC1-positive and non-CPS patients the HR was > 11.86 (P < 0.001). Conclusions: High levels of ERCC1 were associated with non-CPS, suggesting that ERCC1 could be used as a potential indicator of the response to cisplatin and prognosis in ns-TGCTs.
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