Yang Chunxia, Hamajima Nobuyuki, Iwata Hiroji, Saito Toshiko, Matsuo Keitaro, Hirose Kaoru, Inoue Manami, Takezaki Toshiro, Tajima Kazuo
Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan.
Breast Cancer Res. 2002;4(4):R8. doi: 10.1186/bcr445. Epub 2002 Apr 25.
Breast cancer is hormone related, as are cancers of the endometrium, ovary, and prostate. Several studies have suggested that higher extracellular levels of androgens are associated with breast cancer risk, while biological evidence indicates that androgens are protective. The codon 49 alanine to threonine substitution (A49T), codon 89 valine to leucine substitution (V89L) and TA repeat polymorphisms of the steroid 5alpha-reductase type II (SRD5A2) gene are considered functional with respect to enzyme activity converting testosterone into dihydrotestosterone. To test the hypothesis that these three polymorphisms are associated with risk of breast cancer, a case-control study was conducted with patients of Aichi Cancer Center Hospital.
The cases were 237 patients histologically diagnosed with breast cancer, and the controls were 185 noncancer outpatients. DNA from peripheral blood was genotyped by PCR methods.
The threonine allele of A49T was not found in our subjects. Compared with the V/V genotype of V89L, the L/L genotype was associated with a decreased risk (crude odds ratio [OR] = 0.61, 95% confidence interval [CI] = 0.36-1.05). This was also the case for the TA(9/9) genotype, with an OR of 0.58 (95% CI = 0.13-2.63) relative to TA(0/0). Among women with the TA(0/0) genotype, however, the OR for the L/L genotype was 0.46 (95% CI = 0.24-0.88) compared with the V/V genotype, and those with the V/V and TA(0/0) genotypes had the highest risk. The haplotype with the L and TA(9) repeat alleles was not found.
This study is the first to our knowledge focusing on Japanese women, suggesting that SRD5A2 polymorphisms might have an association with breast cancer risk. Further large-sample studies will be required to confirm the association and to assess any interactions with environmental factors.
乳腺癌与激素相关，子宫内膜癌、卵巢癌和前列腺癌也是如此。多项研究表明，细胞外雄激素水平升高与乳腺癌风险相关，而生物学证据表明雄激素具有保护作用。类固醇5α-还原酶II型（SRD5A2）基因的密码子49丙氨酸到苏氨酸替代（A49T）、密码子89缬氨酸到亮氨酸替代（V89L）以及TA重复多态性被认为与将睾酮转化为二氢睾酮的酶活性有关。为了检验这三种多态性与乳腺癌风险相关的假设，对爱知癌症中心医院的患者进行了一项病例对照研究。
病例为237例经组织学诊断为乳腺癌的患者，对照为185例非癌症门诊患者。采用聚合酶链反应（PCR）方法对外周血DNA进行基因分型。
在我们的研究对象中未发现A49T的苏氨酸等位基因。与V89L的V/V基因型相比，L/L基因型与风险降低相关（粗比值比[OR]=0.61，95%置信区间[CI]=0.36-1.05）。TA(9/9)基因型也是如此，相对于TA(0/0)，OR为0.58（95%CI=0.13-2.63）。然而，在TA(0/0)基因型的女性中，与V/V基因型相比，L/L基因型的OR为0.46（95%CI=0.24-0.88），而V/V和TA(0/0)基因型的女性风险最高。未发现带有L和TA(9)重复等位基因的单倍型。
据我们所知，本研究首次聚焦于日本女性，表明SRD5A2多态性可能与乳腺癌风险相关。需要进一步的大样本研究来证实这种关联，并评估与环境因素的任何相互作用。
