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NAT2、XRCC1 和 hOGG1 多态性、吸烟、饮酒与上呼吸道-消化道癌症风险。

NAT2, XRCC1 and hOGG1 polymorphisms, cigarette smoking, alcohol consumption and risk of upper aerodigestive tract cancer.

机构信息

Laboratory of Pharmacogenomics and Genetic Epidemiology (LAFEM), Department of Health, State University of Santa Cruz (UESC), Ilhéus, Brazil.

Laboratory of Human Genetics, Department of Biology, State University of Southwest Bahia (UESB), Jequié, Brazil

出版信息

Anticancer Res. 2014 Jun;34(6):3217-24.

Abstract

AIM

To evaluate associations between polymorphisms of the N-acetyltransferase 2 (NAT2), human 8-oxoguanine glycosylase 1 (hOGG1) and X-ray repair cross-complementing protein 1 (XRCC1) genes and risk of upper aerodigestive tract (UADT) cancer.

PATIENTS AND METHODS

A case-control study involving 117 cases and 224 controls was undertaken. The NAT2 gene polymorphisms were genotyped by automated sequencing and XRCC1 Arg399Gln and hOGG1 Ser326Cys polymorphisms were determined by Polymerase Chain Reaction followed by Restriction Fragment Length Polymorphism (PCR-RFLP) methods.

RESULTS

Slow metabolization phenotype was significantly associated as a risk factor for the development of UADT cancer (p=0.038). Furthermore, haplotype of slow metabolization was also associated with UADT cancer (p=0.014). The hOGG1 Ser326Cys polymorphism (CG or GG vs. CC genotypes) was shown as a protective factor against UADT cancer in moderate smokers (p=0.031). The XRCC1 Arg399Gln polymorphism (GA or AA vs. GG genotypes), in turn, was a protective factor against UADT cancer only among never-drinkers (p=0.048).

CONCLUSION

Interactions involving NAT2, XRCC1 Arg399Gln and hOGG1 Ser326Cys polymorphisms may modulate the risk of UADT cancer in this population.

摘要

目的

评估 N-乙酰基转移酶 2(NAT2)、人类 8-氧鸟嘌呤糖苷酶 1(hOGG1)和 X 射线修复交叉互补蛋白 1(XRCC1)基因多态性与上呼吸道消化道(UADT)癌症风险之间的关联。

患者和方法

进行了一项病例对照研究,纳入 117 例病例和 224 例对照。通过自动测序对 NAT2 基因多态性进行基因分型,通过聚合酶链反应(PCR)后限制性片段长度多态性(PCR-RFLP)方法确定 XRCC1 Arg399Gln 和 hOGG1 Ser326Cys 多态性。

结果

慢速代谢表型显著作为 UADT 癌症发展的危险因素(p=0.038)。此外,慢速代谢的单倍型也与 UADT 癌症相关(p=0.014)。hOGG1 Ser326Cys 多态性(CG 或 GG 与 CC 基因型)在中度吸烟者中表现为 UADT 癌症的保护因子(p=0.031)。相反,XRCC1 Arg399Gln 多态性(GA 或 AA 与 GG 基因型)仅在从不饮酒者中是 UADT 癌症的保护因子(p=0.048)。

结论

NAT2、XRCC1 Arg399Gln 和 hOGG1 Ser326Cys 多态性之间的相互作用可能调节了该人群 UADT 癌症的风险。

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