A Functional Polymorphism (rs10817938) in the XPA Promoter Region Is Associated with Poor Prognosis of Oral Squamous Cell Carcinoma in a Chinese Han Population.
Single nucleotide polymorphisms of XPA gene have been studied in several cancers such as rs10817938, rs2808668. However, the role of XPA polymorphisms in patients with oral squamous cell carcinoma (OSCC) remains unclear. Thus, we analyzed the association of XPA polymorphisms with OSCC risk, clinicopathological characteristics and prognosis in the present study. TaqMan genotyping was used to evaluate the frequency of rs10817938, rs2808668 polymorphisms in OSCC patients. The prognostic significance of these polymorphisms was evaluated using Kaplan-Meier curves, Log-Rank analyses, and the Cox proportional hazard model. Luciferase reporter assay, RT-PCR and western blot were used to determine whether rs10817938 could influence transcription activity and XPA expression. The results showed that individuals carrying TC and CC genotypes had significantly greater risk of developing OSCC (OR = 1.42, 95% CI 1.04-1.93; OR = 2.75, 95% CI 1.32-5.71, respectively) when compared with wild-type TT genotype at rs10817938. OSCC patients with C allele at rs10817938 were more susceptible to lymph metastases, poor pathological differentiation and late TNM stage (OR = 1.67, 95% CI 1.17-2.37; OR = 1.64, 95% CI 1.18-2.28; OR = 1.54, 95% CI 1.11-2.14; respectively). A significant gene-environment interaction between smoking and CC genotype at rs10817938 was observed (COR = 3.60, 95% CI 1.20-10.9) and data also showed that OSCC patients with CC genotype and C allele had worse survival (p<0.001 for both). The T to C substitution at rs10817938 significantly decreased transcription activity of XPA gene, XPA mRNA and protein were also decreased in individuals with C allele at rs10817938. In addition, no significant association of rs2808668 polymorphism with OSCC risk, prognosis could be observed. In conclusion, the present study showed that XPA rs10817938 polymorphism is a functional SNP in vitro and in vivo and a biomarker for poor prognosis in OSCC patients.
Department of Clinical Laboratory, Linyi People's Hospital, Linyi, Shandong, P.R.China.
Chunhai
C
Gao
Department of Clinical Laboratory, Linyi People's Hospital, Linyi, Shandong, P.R.China.
Jinzhu
J
Wang
Jinan Stomatological Hospital, Jinan, Shandong, P.R.China.
Chong
C
Li
Department of Rehabilitation, Linyi People's Hospital, Linyi, Shandong, P.R.China.
Wei
W
Zhang
Jinan Stomatological Hospital, Jinan, Shandong, P.R.China.
Guoxia
G
Liu
D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D016022:Case-Control Studies; D002681:China; D005260:Female; D060005:Genotyping Techniques; D006801:Humans; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D020641:Polymorphism, Single Nucleotide / Q000235:genetics* / Q000502:physiology; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics* / Q000502:physiology; D060888:Real-Time Polymerase Chain Reaction; D016019:Survival Analysis; D051760:Xeroderma Pigmentosum Group A Protein / Q000235:genetics* / Q000502:physiology
C497314:XPA protein, human; D051760:Xeroderma Pigmentosum Group A Protein