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三种热休克蛋白 70 基因多态性与肺癌易感性的关系。

The relationship between three heat shock protein 70 gene polymorphisms and susceptibility to lung cancer.

机构信息

Department of Occupational Health, College of Public Health, Zhengzhou University, Zhengzhou, P.R. China.

出版信息

Clin Chem Lab Med. 2010 Nov;48(11):1657-63. doi: 10.1515/CCLM.2010.304. Epub 2010 Aug 13.

DOI:10.1515/CCLM.2010.304
PMID:20704535
Abstract

BACKGROUND

Heat shock protein 70 (Hsp70) has been shown to act as a chaperone and be associated with a variety of tumors. We investigated HSP70-1 G+190C, HSP70-2 A+1267G, and HSP70-hom T+2437C polymorphisms to assess whether genetic variation in HSP70 plays a role in the occurrence and development of lung cancer.

METHODS

A case-control study was conducted using 159 patients with lung cancer and 202 control subjects. Genomic DNA was typed for HSP70 polymorphisms using polymerase chain reactions with restriction fragment length polymorphism (PCR-RFLP). Unconditional logistic regression was used to estimate the relative risks of lung cancer.

RESULTS

There were significant differences in genotype and allele distributions between patients and controls for the HSP70-1 G+190C polymorphisms with and without adjustment for age, gender, smoking history, drinking history and family history of cancer (p<0.05). No significant differences were found in the polymorphisms of HSP70-2 A+1267G and HSP70-hom T+2437C. The haplotype analysis showed that the G/A/C and C/G/T haplotypes were associated with a significantly increased risk of lung cancer compared to the G/G/T haplotype. After adjustments for other risk factors, such as age, gender, drinking history and family history of cancer, the interactions between the HSP70-1 and HSP70-hom genotypes and smoking were confirmed [I(AB), 2.56 and 5.12, respectively].

CONCLUSIONS

HSP70-1 G+190C may be a functional polymorphism and affect susceptibility to lung cancer, and homozygous C/C genotype may enhance the risk of lung cancer. In addition, smoking along with HSP70-1 G+190C and HSP70-hom T+2437C, may increase the risk of lung cancer.

摘要

背景

热休克蛋白 70(Hsp70)已被证明具有伴侣蛋白的作用,并与多种肿瘤相关。我们研究了 HSP70-1 G+190C、HSP70-2 A+1267G 和 HSP70-hom T+2437C 多态性,以评估 HSP70 的遗传变异是否在肺癌的发生和发展中起作用。

方法

采用病例对照研究,纳入 159 例肺癌患者和 202 例对照。采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)法对 HSP70 多态性进行基因分型。采用非条件 logistic 回归估计肺癌的相对风险。

结果

在调整年龄、性别、吸烟史、饮酒史和癌症家族史后,HSP70-1 G+190C 多态性的基因型和等位基因分布在患者和对照组之间存在显著差异(p<0.05)。HSP70-2 A+1267G 和 HSP70-hom T+2437C 多态性无显著差异。单体型分析显示,与 G/G/T 单体型相比,G/A/C 和 C/G/T 单体型与肺癌的发生风险显著增加相关。在调整其他危险因素(如年龄、性别、饮酒史和癌症家族史)后,证实 HSP70-1 和 HSP70-hom 基因型与吸烟之间存在交互作用[I(AB)分别为 2.56 和 5.12]。

结论

HSP70-1 G+190C 可能是一个功能性多态性,影响肺癌的易感性,纯合 C/C 基因型可能增加肺癌的风险。此外,吸烟与 HSP70-1 G+190C 和 HSP70-hom T+2437C 一起可能增加肺癌的风险。

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