Sarmanová Jana, Sůsová Simona, Gut Ivan, Mrhalová Marcela, Kodet Roman, Adámek Jan, Roth Zdenek, Soucek Pavel
Group for Biotransformations, Center of Occupational Diseases, National Institute of Public Health, Prague 10, Czech Republic.
Eur J Hum Genet. 2004 Oct;12(10):848-54. doi: 10.1038/sj.ejhg.5201249.
We aimed at determining whether any association exists between genetic polymorphisms in epoxide hydrolase (EPHX1), NADPH-quinone oxidoreductase (NQO1), glutathione S-transferases (GSTM1/P1/T1) and individual susceptibility to breast cancer. Polymerase chain reaction-restriction fragment length polymorphism-based genotyping assays were used to determine the frequency of polymorphisms in EPHX1 (exons 3 and 4), NQO1 (exon 6), GSTM1 (deletion), GSTP1 (exon 5), and GSTT1 (deletion) in a case-control study comprised of 238 patients with breast cancer and 313 healthy individuals. The distribution of genotypes in exon 6 of NQO1 was significantly different between the control group and breast cancer cases. Age-adjusted odds ratio (OR) for variant genotype NQO1*2/2 was 3.68 (confidence interval (CI) = 1.41-9.62, P = 0.008). Association of GSTP12/2 genotype as well as that of low EPHX1 activity deduced by combinations of genotypes in exons 3 and 4 with breast cancer was suggestive, but nonsignificant. Individuals simultaneously lacking GSTM1 and carrying at least one GSTP1 variant allele were at significantly higher risk of breast cancer (OR = 2.03, CI = 1.18-3.50, P = 0.010). Combinations of either GSTM1null or GSTP12 with low activity of EPHX1 presented significant risk of breast cancer (OR = 1.88, CI = 1.00-3.52, P = 0.049 and OR = 2.40, CI = 1.15-5.00, P = 0.019, respectively) as well. In conclusion, the results suggest that genetic polymorphisms in biotransformation enzymes may play a significant role in the development of breast cancer.
我们旨在确定环氧化物水解酶（EPHX1）、NADPH-醌氧化还原酶（NQO1）、谷胱甘肽S-转移酶（GSTM1/P1/T1）的基因多态性与个体患乳腺癌易感性之间是否存在关联。在一项病例对照研究中，采用基于聚合酶链反应-限制性片段长度多态性的基因分型检测方法，对238例乳腺癌患者和313名健康个体进行检测，以确定EPHX1（第3和4外显子）、NQO1（第6外显子）、GSTM1（缺失）、GSTP1（第5外显子）和GSTT1（缺失）的多态性频率。NQO1第6外显子的基因型分布在对照组和乳腺癌病例组之间存在显著差异。NQO1*2/2变异基因型的年龄调整优势比（OR）为3.68（置信区间（CI）=1.41-9.62，P = 0.008）。GSTP12/2基因型以及由第3和4外显子基因型组合推断的低EPHX1活性与乳腺癌的关联具有提示性，但不显著。同时缺乏GSTM1且携带至少一个GSTP1变异等位基因的个体患乳腺癌的风险显著更高（OR = 2.03，CI = 1.18-3.50，P = 0.010）。GSTM1缺失或GSTP12与低EPHX1活性的组合也呈现出患乳腺癌风险显著增加（OR分别为1.88，CI = 1.00-3.52，P = 0.049和OR = 2.40，CI = 1.15-5.00，P = 0.019）。总之，结果表明生物转化酶的基因多态性可能在乳腺癌的发生发展中起重要作用。
