MAP3K1基因rs16886165位点多态性与乳腺癌分子亚型遗传易感性的关系

Association between MAP3K1 rs16886165 polymorphism and breast cancer susceptibility according to the intrinsic subtypes in Southern Han Chinese women

目的作为一种高度异质性的恶性肿瘤，乳腺癌不同分子亚型临床特征、形态学表现和复发转移机制各异，但尚无MAP3K1基因多态性与乳腺癌亚型遗传易感性的研究报道。本研究拟深入探讨MAP3K1基因rs16886165位点T—G多态性与中国南方汉族女性散发性乳腺癌及其4种分子亚型易感性的关系。方法应用MassARRAY-IPLEX单核苷酸多态性（single nucleotide polymorphism，SNP）分型技术对2009—0420—2014—07—20来自南方医科大学南方医院（149例）、广州军区总医院（190例）、南昌大学第一附属医院（100倒）、重庆市肿瘤医院（170例）的609例南方汉族女性乳腺癌患者和635名（南方医科大学南方医院333名，广州军区总医院55名，南昌大学第一附属医院90名，重庆市肿瘤医院157名）同期健康女性MAP3K1基因rs16886165位点进行基因分型；sNPStats在线分析软件比较两组在等位基因和基因型分布频率上的差异，非条件Logistic回归评价多态性位点与乳腺癌易感性的相关性；根据雌激素受体（estrogen receptor，ER）、孕激素受体（progesterone receptor，PR）和人表皮生长因子受体2（human epidermal growth factor receptor-2，HER2）的免疫组化结果，将病例分为Luminal A、Luminal B、HER2富集型和三阴型，并进行分层分析。结果Recessive模型（与T／T＋T／G相比）结果提示，MAP3K1基因rs16886165位点G／G基因型与乳腺癌的易感性升高存在统计学关联（OR-1．45，95％CI：1．01～2．08）；但分层分析结果显示，rs16886165位点多态性仅与Luminal B型乳腺癌的易感性存在统计学关联，无论是Co—dominant模型中与T／T基因型相比（ORG／G-2．10，95％CI：1．18～3．73），还是Recessive模型中与T／T＋T／G相比（0R6／G-1．98，95％CI：1．14～3．46），携带G／G基因型患者发生Luminal—B型乳腺癌的风险均显著增加。结论MAP3K1基因rs16886165位点纯合基因型（G／G）与南方汉族女性散发性乳腺癌中的Luminal—B亚型易感性相关。

OBJECTIVE Different intrinsic types of breast cancer vary significantly in terms of incidence, survival, and response to therapy. However, no studies have been conducted to determine whether tumor subtypes modify the association between breast cancer risk and the MAP3K1 rs16886165 polymorphism. We therefore decided to determine the association of MAP3K1 rs16886165 polymorphism and the genetic susceptibility of breast cancer according to the intrinsic subtypes in Southern Han Chinese women. METHODS MassARRAY SNP genotyping system was employed to genotype rs16886165 polymorphism in 609 patients and 635 controls coming from the First Affiliated Hospital of Nanchang University（n= 100）, Nanfang Hospital of Southern Medical University（n= 149）, Guangzhou Military General Hospital （n= 190） and Chongqing Cancer Hospital（n= 170） during the period of April 20,2009 to July 20,2014. Chi-square test was used to compare the distributions of allele and genotype frequencies between breast cancer group and control group. Stratified analyses was performed according to the intrinsic subtypes （Luminal A, Luminal B, HER2-over expression, and triple-negative） defined by the immunohistochemical results of estrogen receptor（ER）, progesterone receptor （PR） and human epidermal growth factor receptor 2 （HER2）. RESULTS Significant associations with breast cancer risk was observed for rs16886165 in the recessive model with OR （95 G CI） of （OR G/G = 1.45, 95G CI： 1.01- 2.08） when compared with T/T＋T/G genotypes. Stratified analyses, however, showed statistically significant association with Luminal- B breast cancer only in both co-dominant model （compared with T/T group） （OR G/G- 2. 10, 95% CI： 1.18-3.73） and recessive model （compared with T/T--T/G group） （OR G/G=1. 98, 95% CI： 1. 14-3.46）. CONCLUSION There is a significant association between rs16886165 GIG genotype and the susceptibility of breast cancer, particularly Luminal-B subtype, in Southern Han Chinese women.