全基因组关联研究(GWAS)表明RASp21蛋白激活因子2(RASA2)等位基因的基因多态性,细胞粘附分子1(CADM1)和缺氧诱导因子1α亚基抑制剂(HIF1AN)与肥胖风险相关。在这项研究中,我们探索了RASA2（rs16851483）的候选SNP之间的相互作用，CADM1（rs12286929）和HIF1AN（rs17094222）和体脂对乳腺癌的风险。应用非条件Logistic回归模型通过比值比（ORs）和95％置信区间（CIs）来测量相关因素与乳腺癌的关联。观察到病例具有统计学上较高的体重指数（BMI≥28kg/m2，OR=1.77），腰围(WC≥90cm,与对照组相比，OR=2.89）和腰臀比（WHR≥0.9，OR=3.41）。RASA2rs16851483T/T纯合子和CADM1rs12286929G/A杂合子的基因型分布在病例和对照之间也存在显著差异,OR为1.68（95%CI：1.10-2.56）和0.80（95%CI：0.64-0.99），分别。此外，基于加性和乘法量表，在三个基因的多态性和身体脂肪之间观察到乳腺癌风险的显着相互作用。我们的研究结果表明，体脂可能在乳腺癌的发展中起重要作用，这种风险可能被某些潜在基因的特定基因型所改变。尤其是中国的肥胖女性。
Genome-wide association studies (GWAS) have indicated that gene polymorphisms in alleles of RAS p21 protein activator 2 (RASA2), cell adhesion molecule 1 (
CADM1) and hypoxia inducible factor 1 alpha subunit inhibitor (HIF1AN) are associated with the risk of obesity. In this study, we explored the interactions between candidate SNPs of RASA2 (rs16851483),
CADM1 (rs12286929) and HIF1AN (rs17094222) and body fatness for breast cancer risk. Unconditional logistic regression models were applied to measure the associations of related factors with breast cancer by odds ratios (ORs) and 95% confidence intervals (CIs). It was observed that cases had a statistically higher body mass index (BMI ≥ 28 kg/m2, OR = 1.77), waist circumference (WC ≥ 90cm, OR = 2.89) and waist-to-hip ratio (WHR ≥ 0.9, OR = 3.41) as compared to controls. Significant differences were also found in the genotype distributions of RASA2 rs16851483 T/T homozygote and
CADM1 rs12286929 G/A heterozygote between cases and controls, with an OR of 1.68 (95% CI: 1.10-2.56) and 0.80 (95% CI: 0.64-0.99), respectively. Furthermore, significant interactions were observed between polymorphisms of three genes and body fatness for the risk of breast cancer based on both additive and multiplicative scales. These results of our study suggest that body fatness possibly plays an important role in the development of breast cancer and this risk might be modified by specific genotypes of some potential genes, especially for obese women in China.
