TNFα - 308G/A多态性作为印度人群中与HPV相关宫颈癌的一个风险因素。
TNFalpha-308G/A polymorphism as a risk factor for HPV associated cervical cancer in Indian population.
作者信息
Kohaar Indu, Thakur Nisha, Salhan Sudha, Batra Swaraj, Singh Veena, Sharma Anita, Sodhani Pushpa, Das B C, Sarkar Debi P, Bharadwaj Mausumi
机构信息
Division of Molecular Genetics & Biochemistry, Institute of Cytology & Preventive Oncology (ICMR), I-7, Sector 39, Noida, India.
出版信息
Cell Oncol. 2007;29(3):249-56. doi: 10.1155/2007/418247.
BACKGROUND
Investigation of the potential association of single nucleotide polymorphisms (SNPs) at -308 G/A and -238 G/A of Tumor necrosis factor alpha (TNFalpha) with susceptibility to HPV-16 associated cervical cancer in Indian women.
METHODS
The study included 165 histologically confirmed cases with 45 precancer and 120 cancer patients and an equal number (165) of healthy controls with normal cervical cytology. PCR-RFLP was employed to analyze TNFalpha promoter polymorphisms, which were confirmed by direct sequencing. Both patients and controls were screened for Human Papillomavirus (HPV) infection.
RESULTS
The frequency of -308 A allele in TNFalpha was significantly higher in cases compared with control subjects (21% in cases vs. 9% in controls; p<0.01), with an odds ratio of 2.7 (95% CI = 1.41-5.15). Also, women carrying A allele for this locus presented 3 times increased susceptibility to HPV 16 infection as evident from carrier genotype distribution between HPV positive cases and control subjects (24% in HPV positive cases vs. 9% in controls; p<0.01; OR = 3.1; 95% CI = 1.60-6.03). No such association was found for TNFalpha-238 (G/A) polymorphism with the risk of development of cervical cancer.
CONCLUSION
It suggests that SNP at -308 (G/A) of TNFalpha promoter may represent an increased risk for HPV infection and development of cervical cancer in Indian women.
背景
研究肿瘤坏死因子α（TNFα）基因-308 G/A和-238 G/A位点的单核苷酸多态性（SNP）与印度女性HPV-16相关宫颈癌易感性之间的潜在关联。
方法
该研究纳入165例经组织学确诊的病例，其中45例为癌前病变患者，120例为癌症患者，以及数量相等（165例）宫颈细胞学正常的健康对照。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）分析TNFα启动子多态性，并通过直接测序进行确认。对患者和对照均进行人乳头瘤病毒（HPV）感染筛查。
结果
与对照相比，病例组中TNFα基因-308 A等位基因的频率显著更高（病例组为21%，对照组为9%；p<0.01），优势比为2.7（95%置信区间=1.41-5.15）。此外，从HPV阳性病例和对照之间的携带者基因型分布情况可以明显看出，携带该位点A等位基因的女性感染HPV 16的易感性增加3倍（HPV阳性病例中为24%，对照组中为9%；p<0.01；OR=3.1；95%置信区间=1.60-6.03）。未发现TNFα -238（G/A）多态性与宫颈癌发生风险之间存在此类关联。
结论
这表明TNFα启动子-308（G/A）位点的SNP可能代表印度女性HPV感染和宫颈癌发生风险增加。
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