Ottini L, Rizzolo P, Zanna I, Silvestri V, Saieva C, Falchetti M, Masala G, Navazio A S, Capalbo C, Bianchi S, Manoukian S, Barile M, Peterlongo P, Caligo M A, Varesco L, Tommasi S, Russo A, Giannini G, Cortesi L, Cini G, Montagna M, Radice P, Palli D
Department of Molecular Medicine, "Sapienza" University of Rome, Viale Regina Elena, 324, 00161, Rome, Italy,
Breast Cancer Res Treat. 2014 Dec;148(3):623-8. doi: 10.1007/s10549-014-3193-2. Epub 2014 Nov 11.
Male breast cancer (MBC) is rare and poorly understood. Like female breast cancer (FBC), MBCs are highly sensitive to hormonal changes, and hyperestrogenism, specifically, represents a major risk factor for MBC. MBC is considered similar to late-onset, post-menopausal estrogen/progesteron receptors positive FBC (ER+/PR+). Sulfotransferase 1A1 (SULT1A1) is an enzyme involved in the metabolism of estrogens. Recently, SULT1A1 common functional polymorphism Arg(213)His (638G>A) variant has been found to be associated with increased breast cancer (BC) risk, particularly in post-menopausal women. For this reason, we decided to explore whether SULT1A1 Arg(213)His could exert an effect on MBC development. The primary aim of this study was to evaluate the influence of the SULT1A1 Arg(213)His polymorphism on MBC risk. The secondary aim was to investigate possible associations with relevant clinical-pathologic features of MBC. A total of 394 MBC cases and 786 healthy male controls were genotyped for SULT1A1 Arg(213)His polymorphism by PCR-RFLP and high-resolution melting analysis. All MBC cases were characterized for relevant clinical-pathologic features. A significant difference in the distribution of SULT1A1 Arg(213)His genotypes was found between MBC cases and controls (P < 0.0001). The analysis of genotype-specific risk showed a significant increased MBC risk in individuals with G/A (OR 1.97, 95% CI 1.50-2.59; P < 0.0001) and A/A (OR 3.09, 95% CI 1.83-5.23; P < 0.0001) genotypes in comparison to wild-type genotype, under co-dominant model. A significant association between SULT1A1 risk genotypes and HER2 status emerged. Results indicate that SULT1A1 Arg(213)His may act as a low-penetrance risk allele for developing MBC and could be associated with a specific tumor subtype associated with HER2 overexpression.
男性乳腺癌（MBC）较为罕见且了解甚少。与女性乳腺癌（FBC）一样，MBC对激素变化高度敏感，尤其是高雌激素血症是MBC的主要危险因素。MBC被认为与晚发型、绝经后雌激素/孕激素受体阳性的FBC（ER+/PR+）相似。磺基转移酶1A1（SULT1A1）是一种参与雌激素代谢的酶。最近，发现SULT1A1常见的功能性多态性Arg(213)His（638G>A）变体与乳腺癌（BC）风险增加有关，尤其是在绝经后女性中。因此，我们决定探究SULT1A1 Arg(213)His是否会对MBC的发展产生影响。本研究的主要目的是评估SULT1A1 Arg(213)His多态性对MBC风险的影响。次要目的是调查与MBC相关临床病理特征的可能关联。通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）和高分辨率熔解分析对394例MBC病例和786例健康男性对照进行SULT1A1 Arg(213)His多态性基因分型。对所有MBC病例的相关临床病理特征进行了描述。在MBC病例和对照之间发现SULT1A1 Arg(213)His基因型分布存在显著差异（P < 0.0001）。基因型特异性风险分析显示，与野生型基因型相比，在共显性模型下，携带G/A（比值比1.97，95%置信区间1.50 - 2.59；P < 0.0001）和A/A（比值比3.09，95%置信区间1.83 - 5.23；P < 0.0001）基因型的个体患MBC的风险显著增加。SULT1A1风险基因型与HER2状态之间存在显著关联。结果表明，SULT1A1 Arg(213)His可能是MBC发生的低外显率风险等位基因，并且可能与HER2过表达相关的特定肿瘤亚型有关。
