Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Florence, Italy.
J Cell Mol Med. 2013 May;17(5):605-7. doi: 10.1111/jcmm.12043.
SULT1A1, a member of sulfotransferase superfamily, is a drug and hormone metabolizing enzyme involved in the metabolism of a variety of potential mammary carcinogens of endogenous and exogenous origin. Interestingly, the metabolic activity of SULT1A1 can be affected by variations in gene copy number. Male Breast Cancer (MBC) is a rare disease and less investigated disease compared to female BC (FBC). As in FBC, the concurrent effects of genetic risk factors, particularly BRCA2 mutations, increased exposure to estrogens and environmental carcinogens play a relevant role in MBC. By quantitative real-time PCR with TaqMan probes, we investigated the presence of SULT1A1 gene copy number variations (CNVs) in a series of 72 MBCs. SULT1A1 gene deletion was observed in 10 of the 72 MBCs (13.9%). In a multivariate analysis association between BRCA2 mutation and SULT1A1 gene deletion emerged (p = 0.0005). Based on the evidence that the level of SULT1A1 enzyme activity is correlated with CNV, our data suggest that in male breast tumors SULT1A1 activity may be decreased. Thus, it can be hypothesized that in a proportion of MBCs, particularly in BRCA2-associated MBCs, the level of estrogens and environmental carcinogens exposure might be increased suggesting a link between gene and environmental exposure in the pathogenesis of MBC.
SULT1A1 是磺基转移酶超家族的成员，是一种参与多种内源性和外源性潜在乳腺癌致癌物质代谢的药物和激素代谢酶。有趣的是，SULT1A1 的代谢活性可以受到基因拷贝数变异的影响。男性乳腺癌（MBC）是一种罕见疾病，与女性乳腺癌（FBC）相比，研究较少。与 FBC 一样，遗传风险因素的共同作用，特别是 BRCA2 突变、雌激素和环境致癌物暴露的增加，在 MBC 中发挥着重要作用。通过使用 TaqMan 探针的定量实时 PCR，我们在一系列 72 例 MBC 中研究了 SULT1A1 基因拷贝数变异（CNV）的存在。在 72 例 MBC 中，有 10 例（13.9%）观察到 SULT1A1 基因缺失。在多变量分析中，BRCA2 突变与 SULT1A1 基因缺失之间存在关联（p = 0.0005）。基于 SULT1A1 酶活性水平与 CNV 相关的证据，我们的数据表明，在男性乳腺癌肿瘤中，SULT1A1 活性可能降低。因此，可以假设在一部分 MBC 中，特别是在与 BRCA2 相关的 MBC 中，雌激素和环境致癌物暴露水平可能会增加，这表明基因和环境暴露在 MBC 的发病机制中存在联系。
