Aim: Individuals differ in their inherited tendency to develop cancer. This has been suggested to be due to genetic variations between individuals. Single-nucleotide polymorphisms (SNPs) are the most common form of genetic variations found in the human population. The aim of this study was to investigate the association between 10 SNPs in genes involved in cell cycle control and DNA repair (p21 C31A, p53 G72C, ATM G1853A, XRCC1 G399A, XRCC3 C241T, Ku80 A2790G, DNA Ligase IV C9T, DNA-PKcs A3434G, TGF-beta T10C, MDM2 promoter T309G) and the risk to develop head and neck cancer. Materials and Methods: A cohort of 407 individuals (156 cancer patients and 251 controls) was included. DNA was extracted from peripheral blood. SNPs were genotyped by direct sequencing. Results: Data showed significant allelic associations for p21 C31A (p=0.04; odds ratio [OR]=1.44; confidence interval [CI]: 1.02-2.03), Ku80 A2790G (p=0.04; OR=1.5; CI: 1.01-2.23), and MDM2 T309G (p=0.0003; OR=0.58; CI: 0.43-0.78) and head and neck cancer occurrence. Both cancer cases and controls were in Hardy-Weinberg equilibrium. Conclusion: SNPs can be associated with head and neck cancer in the Saudi population. The p21 C31A, Ku80 A2790G, and MDM2 T309G SNPs could be used as genetic biomarkers to screen individuals at high cancer risk.
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References
1.
AlsbeihG, Al-HarbiN, Al-HadyanKet al.2010. Association between normal tissue complications after radiotherapy and polymorphic variations in TGFB1 and XRCC1 genes. Radiat Res, 173:505-511.
2.
Authority NCR. 2006. Cancer Incidence Report: Saudi Arabia, Ministry of Health, Saudi Cancer Registry.
3.
BauDT, FuYP, ChenSTet al.2004. Breast cancer risk and the DNA double-strand break end-joining capacity of nonhomologous end-joining genes are affected by BRCA1. Cancer Res, 64:5013-5019.
4.
BettendorfO, PiffkoJ, BankfalviA. 2004. Prognostic and predictive factors in oral squamous cell cancer: important tools for planning individual therapy?Oral Oncol, 40:110-119.
5.
BondGL, HuW, BondEEet al.2004. A single nucleotide polymorphism in the MDM2 promoter attenuates the p53 tumor suppressor pathway and accelerates tumor formation in humans. Cell, 119:591-602.
6.
BrookesAJ. 1999. The essence of SNPs. Gene, 234:177-186.
7.
ChiuCF, WangCH, WangCLet al.2008. A novel single nucleotide polymorphism in XRCC4 gene is associated with gastric cancer susceptibility in Taiwan. Ann Surg Oncol, 15:514-518.
8.
ChungCH, GillisonML. 2009. Human papillomavirus in head and neck cancer: its role in pathogenesis and clinical implications. Clin Cancer Res, 15:6758-6762.
9.
FacherEA, BecichMJ, DekaA, LawJC. 1997. Association between human cancer and two polymorphisms occurring together in the p21Waf1/Cip1 cyclin-dependent kinase inhibitor gene. Cancer, 79:2424-2429.
10.
HashibeM, BrennanP, BenhamouSet al.2007. Alcohol drinking in never users of tobacco, cigarette smoking in never drinkers, and the risk of head and neck cancer: pooled analysis in the International Head and Neck Cancer Epidemiology Consortium. J Natl Cancer Inst, 99:777-789.
11.
HauptY, MayaR, KazazA, OrenM. 1997. Mdm2 promotes the rapid degradation of p53. Nature, 387:296-299.
12.
HoT, WeiQ, SturgisEM. 2007. Epidemiology of carcinogen metabolism genes and risk of squamous cell carcinoma of the head and neck. Head Neck, 29:682-699.
13.
HsuCF, TsengHC, ChiuCFet al.2009. Association between DNA double strand break gene Ku80 polymorphisms and oral cancer susceptibility. Oral Oncol, 45:789-793.
14.
HuZ, JinG, WangLet al.2007. MDM2 promoter polymorphism SNP309 contributes to tumor susceptibility: evidence from 21 case-control studies. Cancer Epidemiol Biomarkers Prev, 16:2717-2723.
15.
HuZ, MaH, LuDet al.2006. Genetic variants in the MDM2 promoter and lung cancer risk in a Chinese population. Int J Cancer, 118:1275-1278.
16.
HuangSP, WuWJ, ChangWSet al.2004. p53 Codon 72 and p21 codon 31 polymorphisms in prostate cancer. Cancer Epidemiol Biomarkers Prev, 13:2217-2224.
17.
KubbutatMH, JonesSN, VousdenKH. 1997. Regulation of p53 stability by Mdm2. Nature, 387:299-303.
18.
LiG, ZhaiX, ZhangZet al.2006. MDM2 gene promoter polymorphisms and risk of lung cancer: a case-control analysis. Carcinogenesis, 27:2028-2033.
19.
LukasJ, GroshenS, SaffariBet al.1997. WAF1/Cip1 gene polymorphism and expression in carcinomas of the breast, ovary, and endometrium. Am J Pathol, 150:167-175.
20.
MaH, HuZ, ZhaiXet al.2006. Polymorphisms in the MDM2 promoter and risk of breast cancer: a case-control analysis in a Chinese population. Cancer Lett, 240:261-267.
21.
MillikanRC, HeardK, WinkelSet al.2006. No association between the MDM2-309 T/G promoter polymorphism and breast cancer in African-Americans or Whites. Cancer Epidemiol Biomarkers Prev, 15:175-177.
22.
MomandJ, ZambettiGP, OlsonDCet al.1992. The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation. Cell, 69:1237-1245.
23.
MoussesS, OzcelikH, LeePDet al.1995. Two variants of the CIP1/WAF1 gene occur together and are associated with human cancer. Hum Mol Genet., 4:1089-1092.
24.
OlinerJD, PietenpolJA, ThiagalingamSet al.1993. Oncoprotein MDM2 conceals the activation domain of tumour suppressor p53. Nature, 362:857-860.
25.
ParkinDM, BrayF, FerlayJ, PisaniP. 2005. Global cancer statistics, 2002. CA Cancer J Clin, 55:74-108.
26.
PhangBH, LinnYC, LiH, SabapathyK. 2008. MDM2 SNP309 G allele decreases risk but does not affect onset age or survival of Chinese leukaemia patients. Eur J Cancer, 44:760-766.
27.
PowellBL, van StaverenIL, RooskenPet al.2002. Associations between common polymorphisms in TP53 and p21WAF1/Cip1 and phenotypic features of breast cancer. Carcinogenesis, 23:311-315.
28.
SchmidtMK, ReinckeS, BroeksAet al.2007. Do MDM2 SNP309 and TP53 R72P interact in breast cancer susceptibility? A large pooled series from the breast cancer association consortium. Cancer Res, 67:9584-9590.
29.
ShioharaM, el-DeiryW, WadaMet al.1994. Absence of WAF1 mutations in a variety of human malignancies. Blood, 84:3781-3784.
30.
SiemiatyckiJ, RichardsonL, StraifKet al.2004. Listing occupational carcinogens. Environ Health Perspect, 112:1447-1459.
31.
YangM, GuoY, ZhangXet al.2007. Interaction of P53 Arg72Pro and MDM2 T309G polymorphisms and their associations with risk of gastric cardia cancer. Carcinogenesis, 28:1996-2001.
32.
ZhouG, ZhaiY, CuiYet al.2007. MDM2 promoter SNP309 is associated with risk of occurrence and advanced lymph node metastasis of nasopharyngeal carcinoma in Chinese population. Clin Cancer Res, 13:2627-2633.
