智利人群中CYP1A1和GSTM1的单基因型或联合基因型与前列腺癌之间的正相关关系。

Positive correlation between single or combined genotypes of CYP1A1 and GSTM1 in relation to prostate cancer in Chilean people.

作者信息

Acevedo Cristian, Opazo Jose Luis, Huidobro Christian, Cabezas Juan, Iturrieta Jeannette, Quiñones Sepúlveda Luis

机构信息

Laboratory of Chemical Carcinogenesis and Pharmacogenetics, Programe of Molecular and Clinical Pharmacology, ICBM, Faculty of Medicine, University of Chile, Santiago, Chile.

出版信息

Prostate. 2003 Oct 1;57(2):111-7. doi: 10.1002/pros.10274.

DOI:10.1002/pros.10274

PMID:12949934

Abstract

BACKGROUND

The prostate cancer is a slowly progressing disease that begins decades prior to diagnosis. It has been suggested that there might be differences in susceptibility due to genetic polymorphisms in biotransformation enzyme genes. In the present work, associations between CYP1A1(Msp1), GSTM1(-/-) polymorphisms, and prostate cancer were analyzed in a case-control study.

METHODS

Genomic DNA was isolated from peripheral blood samples, collected on EDTA. PCR-RFLP was used to determine simultaneously Msp1 and GSTM1(-/-) polymorphisms.

RESULTS

In cancer patients, frequency of m2 variant allele (0.377) and GSTM1(-/-) (0.362) showed statistically significant increases compared to the control group (0.262 and 0.227, respectively). The estimate relative risks (OR) were higher for individuals carrying combined CYP1A1 and GSTM1 rare genotypes, in relation to individuals carrying CYP1A1 or GSTM1 alone. Multivariate logistic regression analysis including confounding factors (age, digital examination, and PSA antigen) showed even higher risk for individuals carrying m2m2 genotype (OR = 3.99; 95% CI, 1.27-12.54), GST(-/-) genotype (OR = 2.75; 95% CI, 1.31-5.79), and m2m2/GST(-) genotype (OR = 16.63; 95% CI, 1.67-165.48).

CONCLUSIONS

Taken together, these findings suggest that Chilean people carrying single or combined GSTM1 and CYP1A1 polymorphisms are more susceptible to prostate cancer.

摘要

背景

前列腺癌是一种进展缓慢的疾病，在诊断前数十年就已开始。有人提出，由于生物转化酶基因的遗传多态性，易感性可能存在差异。在本研究中，通过病例对照研究分析了CYP1A1（Msp1）、GSTM1（-/-）多态性与前列腺癌之间的关联。

方法

从用乙二胺四乙酸（EDTA）采集的外周血样本中分离基因组DNA。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法同时检测Msp1和GSTM1（-/-）多态性。

结果

与对照组相比，癌症患者中m2变异等位基因频率（0.377）和GSTM1（-/-）频率（0.362）有统计学意义的显著增加（对照组分别为0.262和0.227）。与单独携带CYP1A1或GSTM1罕见基因型的个体相比，同时携带CYP1A1和GSTM1罕见基因型的个体估计相对风险（OR）更高。包括混杂因素（年龄、直肠指检和前列腺特异性抗原[PSA]）的多变量逻辑回归分析显示，携带m2m2基因型（OR = 3.99；95%可信区间[CI]，1.27 - 12.54）、GST（-/-）基因型（OR = 2.75；95%CI，1.31 - 5.79）和m2m2/GST（-）基因型（OR = 16.63；95%CI，1.67 - 165.48）的个体风险更高。