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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○R-IPLEX单核苷酸多态性(single nucleotide polymorphism,SNP)分型技术对2009-04-20-2014-07-20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例)、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(ORG/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 As a highly heterogeneous malignant tumor, the clinical features, morphological features and recurrence and metastasis mechanisms of different molecular subtypes of breast cancer are different, but there is no report of the genetic polymorphism of MAP3K1 and the genetic susceptibility of breast cancer subtypes . This study intends to in-depth study of MAP3K1 gene rs16886165 T → G polymorphism and southern Chinese Han women with sporadic breast cancer and its four subtypes of susceptibility to the relationship. Methods The genotyping technique of MassARRAY ○ R-IPLEX single nucleotide polymorphism (SNP) Sixty-nine southern Chinese women with breast cancer and six hundred and sixty-five southern Chinese women (333 Southern Hospital of Southern Medical University, Guangzhou Military Region General Hospital, Shanghai Medical University Hospital, 190 First Affiliated Hospital of Nanchang University, 55, No. 1 Affiliated Hospital of Nanchang University and No. 157 Hospital of Chongqing Cancer Hospital) were genotyped at the rs16886165 locus of healthy women with MAP3K1 in the same period. SNPStats online analysis software was used to compare the distribution frequencies of alleles and genotypes The difference and non-conditional logistic regression were used to evaluate the association between polymorphic loci and susceptibility to breast cancer. According to estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor Immunohistochemical results of human epidermal growth factor receptor-2 (HER2) were divided into Luminal A, Luminal B, HER2-enriched and triple-negative and stratified. Results Recessive model (compared with T / T + T / G) suggested that there was a statistically significant association between the G / G genotype of rs16886165 at MAP3K1 and the increased susceptibility to breast cancer (OR = 1.45, 95% CI: 1.01 ~ 2.08). However, the stratified analysis showed that rs16886165 polymorphism was only associated with the susceptibility to Luminal B breast cancer, both in the Co-dominant and T / T genotypes (ORG / G = 2.10, 95% CI: 1.18 to 3.73), or in the Recessive model compared with T / T + T / G The risk of developing Luminal-B breast cancer is significantly increased. Conclusion The homozygous genotype rs16886165 (G / G) of MAP3K1 gene is associated with the susceptibility to Luminal-B subtype in sporadic breast cancer in southern Han Chinese women.