DNA repair genes XPC, XPG polymorphisms: relation to the risk of colorectal carcinoma and therapeutic outcome with Oxaliplatin-based adjuvant chemotherapy.
Xeroderma pigmentosum complementation group C and G (XPC, XPG) play important roles in DNA damage repairing machinery. Genetic variations in the XPC and XPG may be associated with increased risk for colorectal carcinoma (CRC). In this study, we evaluated the relation between the XPC Lys939Gln, XPG Asp1104His polymorphisms, and CRC susceptibility in a population-based case-control study, which included 1,028 CRC cases and 1,085 controls. Compared with the corresponding wild genotypes, we found that individuals with at least one copy of the XPC Lys939Gln (AC or CC genotype) and XPG Asp1104His (GC or CC genotype) had an increased risk for CRC. In addition, the variant genotypes of the XPC Lys939Gln AC/CC (P = 0.027) or XPG Asp1104His GC/CC (P = 0.003) reduced the elevation of preoperative carcinoembryonic antigen (CEA) level. Moreover a significantly longer progression-free survival (PFS) after Oxaliplatin-based adjuvant chemotherapy was observed in patients with XPG Asp1104His wide-type GG genotype (n = 432, Log-rank test: P = 0.033). Cox proportional hazards analyses demonstrated that variant genotypes of XPG Asp1104His [hazard ratio (HR) = 1.692, 95% confidence interval (95%CI): 1.202-2.383, P = 0.003] as well as pathology grade (HR = 2.545, 95%CI: 2.139-3.030, P < 0.001), and lymph node metastases (HR = 1.851, 95%CI: 1.306-2.625, P < 0.001) were predictive of shorter PFS for the CRC patients with Oxaliplatin-based adjuvant chemotherapy. In conclusion, the current data suggested that XPC Lys939Gln and XPG Asp1104His polymorphisms might contribute to the identification of patients with increased risk for CRC.
Department of Pharmacology, School of Pharmaceutical Sciences, China Medical University, Shenyang, PR China.
Duo
D
Liu
Hui-zhe
HZ
Wu
Yi-ning
YN
Zhang
Hui
H
Kang
Ming-jun
MJ
Sun
En-hua
EH
Wang
Xiu-li
XL
Yang
Min-qiong
MQ
Lian
Zhao-jin
ZJ
Yu
Lin
L
Zhao
Olufunmilayo I
OI
Olopade
Min-jie
MJ
Wei
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood; D002272:Carcinoembryonic Antigen / Q000097:blood; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D004260:DNA Repair / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D018572:Disease-Free Survival; D004720:Endonucleases / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics; D009944:Organoplatinum Compounds / Q000627:therapeutic use*; D000077150:Oxaliplatin; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D014157:Transcription Factors / Q000235:genetics; D016896:Treatment Outcome; D014983:Xeroderma Pigmentosum / Q000235:genetics; D055815:Young Adult; D000099250:DNA Excision Repair Protein ERCC-5
D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D004268:DNA-Binding Proteins; D004720:Endonucleases; D009687:Nuclear Proteins; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D014157:Transcription Factors; D000099250:DNA Excision Repair Protein ERCC-5; C086984:XPC protein, human