The role of the fat mass and obesity associated gene (FTO) in breast cancer risk.
The role of the fat mass and obesity associated gene (FTO) in breast cancer risk.
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DOI：
10.1186/1471-2350-12-52
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发表时间：
2011-04-13
影响因子：
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通讯作者：
Mantzoros C
中科院分区：
文献类型：
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作者：
Kaklamani V;Yi N;Sadim M;Siziopikou K;Zhang K;Xu Y;Tofilon S;Agarwal S;Pasche B;Mantzoros C
肥胖已被证明会增加乳腺癌的风险。FTO是一个新的基因，已通过全基因组关联研究（GWAS）被确定为与肥胖相关。我们的目的是评估FTO在乳腺中的组织表达以及FTO SNP在预测乳腺癌风险中的作用。我们对354例乳腺癌病例和364例对照进行了病例对照研究。这项研究在西北大学进行。我们研究了FTO内含子1的单核苷酸多态性（SNPs）在乳腺癌风险中的作用。我们对病例组和对照组进行了四种SNP的基因分型：rs7206790、rs8047395、rs9939609和rs1477196。我们还评估了FTO在正常和恶性乳腺组织中的组织表达。我们发现所有SNPs都与乳腺癌风险显著相关，其中rs1477196显示出最强的相关性。我们发现FTO在正常和恶性乳腺组织中都有表达。我们发现FTO基因型提供了预测乳腺癌风险的强大分类器，并且具有上位相互作用的模型进一步提高了预测准确性，其受试者操作特征（ROC）曲线为0.68。总之，我们已经表明FTO在恶性和正常乳腺组织中的显著表达，并且内含子1中的FTO SNP与乳腺癌风险显著相关。此外，这些FTO SNP是预测乳腺癌风险的强大分类器。
Obesity has been shown to increase breast cancer risk. FTO is a novel gene which has been identified through genome wide association studies (GWAS) to be related to obesity. Our objective was to evaluate tissue expression of FTO in breast and the role of FTO SNPs in predicting breast cancer risk. We performed a case-control study of 354 breast cancer cases and 364 controls. This study was conducted at Northwestern University. We examined the role of single nucleotide polymorphisms (SNPs) of intron 1 of FTO in breast cancer risk. We genotyped cases and controls for four SNPs: rs7206790, rs8047395, rs9939609 and rs1477196. We also evaluated tissue expression of FTO in normal and malignant breast tissue. We found that all SNPs were significantly associated with breast cancer risk with rs1477196 showing the strongest association. We showed that FTO is expressed both in normal and malignant breast tissue. We found that FTO genotypes provided powerful classifiers to predict breast cancer risk and a model with epistatic interactions further improved the prediction accuracy with a receiver operating characteristic (ROC) curves of 0.68. In conclusion we have shown a significant expression of FTO in malignant and normal breast tissue and that FTO SNPs in intron 1 are significantly associated with breast cancer risk. Furthermore, these FTO SNPs are powerful classifiers in predicting breast cancer risk.