Role of common ERCC1 polymorphisms in cisplatin‐resistant epithelial ovarian cancer patients: A study in Chinese cohort

Abstract

Epithelial ovarian cancer (EOC) contributes the majority of death cases among various ovarian malignancies. Although a standard method of treatment is the surgical removal of malignant tissue followed by platinum‐based chemotherapy, a group of patients does not respond appropriately to cisplatin. An appropriate response to cisplatin has been linked with the nucleotide excision repair mechanism. The present study aims to investigate the role of polymorphisms in DNA repair genes, excision repair cross‐complementation group 1 (ERCC1) with susceptibility to EOC development and tumour response to platinum‐based chemotherapy in Chinese EOC patients. Patients (n = 559) reporting to the Department of Oncology and general surgery, the First Affiliated Hospital of Kunming Medical University, were enrolled in the study. Three hundred twenty‐three healthy controls hailing from similar geographical areas without a history of cancer enrolled as healthy controls. Excision repair cross‐complementation group 1 polymorphisms (rs11615, rs3212986, rs735482, rs2336219, rs3212980, rs3212964, rs3212961 and rs2298881) were genotyped by appropriate methods. Distribution of genotypes and allele for ERCC1 polymorphisms (rs11615, rs3212986, rs735482, rs2336219, rs3212980, rs3212964, rs3212961 and rs2298881) were comparable among healthy controls and EOC patients. Interestingly, homozygous mutant and the minor allele for rs11615 and rs3212986 polymorphisms were significantly higher in nonresponder EOC patients when compared to those with a proper response to cisplatin treatment. The prevalence of other SNPs was comparable among the two treated clinical categories. Furthermore, combined genotype revealed significant association of rs11615: TT/ rs3212986: AA genotype combination with cisplatin nonresponder. Variants of rs11615, rs3212986 polymorphisms are associated with cisplatin resistance in Chinese EOC patients. Combined rs11615 and rs3212986 genotypes can be used as a predictive biomarker for platinum‐based chemotherapy outcomes.

DNA Repair and Ovarian Carcinogenesis: Impact on Risk, Prognosis and Therapy Outcome

“…Ishibashi et al reported that in OvC cell lines, tyrosine kinase with immunoglobulin-like and EGF like domains 1 (TIE1) promotes XPC-dependent NER and this leads to decreased susceptibility to cisplatin-induced cell death [158]. Last but not least, a study in 559 EOC patients showed an association of ERCC1 polymorphisms rs11615 and rs3212986 with cisplatin resistance [159]. Beyond the PARP1 well-established role in BER, this protein is also known to regulate the NER system by its association with XPA (for more details, see Section 4) [160].…”

“…Cancers 2020, 12, 1713 15 of 37 [159]. Beyond the PARP1 well-established role in BER, this protein is also known to regulate the NER system by its association with XPA (for more details, see Section 4) [160].…”

Effect of ERCC1 polymorphisms on the response to platinum-based chemotherapy: A systematic review and meta-analysis based on Asian population

“…The rs3212986 polymorphism has a wild-type C allele and variant A allele. A total of 9 studies [ 16 , 17 , 20 , 24 , 25 , 33 – 36 ], involving 2545 patients were included. There are 7 studies on gastric cancer, 1 on lung cancer, 1 on ovarian cancer and 1 on osteosarcoma.…”

Haplotypes of single cancer driver genes and their local ancestry in a highly admixed long-lived population of Northeast Brazil

“…, 2020 ; Salimzadeh et al , 2020 ; Zhao et al , 2019 ) rs1052555 ( Yang et al , 2005 ; Li et al , 2020 ) GG (7.0%) 1 59.91 0.622 0.96-1.0 GA (14.8%) 1 59.91 0.622 0.96-1.0 ERCC1 AGCT (45.3%) rs1046282 rs2336219 rs3212986 rs3212980 1 9.21 0.132 0.83-1.0 rs1046282 ( Yin et al , 2013 ) rs2336219 ( Ricci et al , 2010 ; Dai et al , 2019a ) rs3212986 ( He et al , 2018 ; Chaszczewska-Markowska et al , 2019 ; Gholami et al. , 2019 ; Yang et al , 2019 ; Bao et al. , 2020 ; Grenda et al , 2020 ) rs3212980 ( Yin et al , 2013 ).…”