Polymorphisms in ERCC5 rs17655 and ERCC1 rs735482 Genes Associated with the Survival of Male Patients with Postoperative Oral Squamous Cell Carcinoma Treated with Adjuvant Concurrent Chemoradiotherapy

Abstract

The nucleotide excision repair (NER) pathway plays a major role in the repair of DNA damaged by exogenous agents, such as chemotherapeutic and radiotherapeutic agents. Thus, we investigated the association between key potentially functional single nucleotide polymorphisms (SNPs) in the NER pathway and clinical outcomes in oral squamous cell carcinoma (OSCC) patients treated with concurrent chemoradiotherapy (CCRT). Thirteen SNPs in five key NER genes were genotyped in 319 male OSCC patients using iPLEX MassARRAY. Cox proportional hazards models and Kaplan–Meier survival curves were used to estimate the risk of death or recurrence. Carriers of the XPC rs2228000 TT genotype showed a borderline significant increased risk of poor overall survival under the recessive model (hazard ratio (HR) = 1.81, 95% confidence interval (CI) = 0.99–3.29). The CC genotypes of ERCC5 rs17655 (HR = 1.54, 95% CI = 1.03–2.29) and ERCC1 rs735482 (HR = 1.65, 95% CI = 1.06–2.58) were associated with an increased risk of worse disease-free survival under the recessive model. In addition, participants carrying both the CC genotypes of ERCC5 rs17655 and ERCC1 rs735482 exhibited an enhanced susceptibility for recurrence (HR = 2.60, 95% CI = 1.11–6.09). However, no statistically significant interaction was observed between them. Our findings reveal that the ERCC5 rs17655 CC and ERCC1 rs735482 CC genotypes were associated with an increased risk of recurrence in male patients with OSCC treated with CCRT. Therefore, CCRT may not be beneficial, and alternative treatments are required for such patients.

Expression and Genetic Polymorphisms of ERCC1 in Chinese Han Patients with Oral Squamous Cell Carcinoma

“…As there are many SNPs in the ERCC1 gene and only a few SNPs may contribute to the occurrence of cancer, it is extremely important to choose the right candidate polymorphisms to test an association with OSCC. In view of the previous reports, we chose four SNPs in the ERCC1 gene including rs11615, rs3212948, rs3212961, and rs735482 which are reported to be associated with certain cancers [ 12 , 13 , 20 , 23 ]. In our study, we did not found a significant association between four SNPs in the ERCC1 gene and susceptibility of OSCC.…”

“…In a meta-analysis, it was concluded that ERCC1 C118T (rs11615) and C8092A could predict both the objective response rate as well as overall survival for platinum-based chemotherapy in Asian NSCLC patients through the analysis of 33 studies including 5373 patients [ 22 ]. One study from Taiwan found that the ERCC1 rs735482 CC genotype is associated with an increased risk of recurrence in male patients with OSCC treated with concurrent chemoradiotherapy [ 23 ].…”

“…Until now, no studies have been reported concerning the association of ERCC1 gene polymorphisms and OSCC, and only one has addressed the role of ERCC1 rs735482 in the response to chemoradiotherapy in OSCC [ 23 ], and this was therefore the subject of the study reported here. In view of earlier studies on ERCC1 gene associations with cancer as well as the response to chemotherapy, we chose four ERCC1 SNPs including rs11615, rs3212948, rs3212961, and rs735482 in our study.…”

Gene-environment and gene-gene interactions between CHRNA3 rs1051730, XRCC1 rs25487, and ERCC1 rs735482 variants highly elevate the risk of lung cancer

“…Subjects with low expression and/or activity of DNA repair enzymes have impaired ability to remove tobacco-induced DNA damage and are more likely to develop lung cancer. Excision repair cross complementing group 1 (ERCC1) and X-ray repair crosscomplementing group 1 (XRCC1) enzymes are needed to clear DNA damage and have been highlighted as potential biomarkers of clinical outcome in cancer [6][7][8][9][10].…”

Interaction of DNA Repair Gene XPC With Smoking and Betel Quid Chewing Behaviors of Oral Cancer

“…In 2007, Wang and colleagues provided evidence showing that XPC rs2228000 genotypes have conferred a protective effect on oral cancer susceptibility, evident in older individuals, women, ever smokers, and never drinkers (20). In 2019, Senghore and colleagues found that the TT genotype at XPC rs2228000 increased the risk of poor overall survival at borderline significance compared to the CC+CT genotypes (HR=1.86, 95% CI=0.97-3.56), while XPC rs2228000 or XPC rs2228001 genotypes could not serve as good predictors for oral cancer susceptibility (21). Based on the limited literature on XPC and oral cancer, we are keen to assess whether rs2228000 and rs2228001 polymorphisms of XPC are associated with the risk of oral cancer in Taiwan.…”