Abstract
Xeroderma pigmentosum group G (XPG), one of key components of nucleotide excision repair pathway (NER), is involved in excision repair of UV-induced DNA damage. Single nucleotide polymorphisms (SNPs) in the XPG gene have been reported to associate with the clinical outcome of various cancer patients. We aimed to assess the impact of four potentially functional SNPs (rs2094258 C>T, rs2296147 T>C, rs751402 G>A, and rs873601 G>A) in the XPG gene on prognosis in colorectal cancer (CRC) patients. A total of 1901 patients diagnosed with pathologically confirmed CRC were genotyped for four XPG polymorphisms. Cox proportional hazards model analysis controlled for several confounding factors was conducted to compute hazard ratios (HRs) and 95% confidence intervals (CIs). Of the four included SNPs, only rs2296147 was shown to significantly affect progression-free survival (PFS) in CRC. Patients carrying rs2296147 CT/TT genotype had a significantly shorter median 10 years PFS than those carrying CC genotype (88.5 months vs. 118.1 months), and an increased progression risk were observed with rs2296147 (HR = 1.324, 95% CI = 1.046–1.667). Moreover, none of the four SNPs were associated with overall survival. In conclusion, our study showed that XPG rs2296147 CT/TT variants conferred significant survival disadvantage in CRC patients in term of PFS. XPG rs2296147 polymorphism could be predictive of unfavorable prognosis of CRC patients.
Highlights
Colorectal cancer (CRC) is the third most common cancer and the fourth leading cause of cancer-related death in the world
Surgery is used to treat the early stage of CRC, while the combination of 5-fluorouracil (5-FU), irinotecan, and oxaliplatin (FOLFOXIRI) is administrated to late-stage patients as the standard first-line chemotherapy to improve the prognosis [2]
We found that Xeroderma pigmentosum group G (XPG) rs2296147 CT/TT genotypes were correlated with poor 10-year progression-free survival (PFS) in CRC when compared with CC genotype
Summary
Colorectal cancer (CRC) is the third most common cancer and the fourth leading cause of cancer-related death in the world (http://globocan.iarc.fr/Pages/fact_sheets_ cancer.aspx). Incidence of CRC dramatically varies from region to region It ranks fifth in the commonly diagnosed malignancies in China, with 253, 427 new cases diagnosed and 139, 416 cancer deaths in 2012 It ranks the third in the commonly diagnosed malignancies in males and the second in females, with 1.4 million new cases diagnosed and 693, 900 cancer deaths in 2012 [1]. The prognosis of colorectal cancer has been gradually improved over the past decades, with a 5-year relative survival of 65% and less than 50% in highand low-income countries, respectively [3]
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