The role of the fat mass and obesity associated gene (FTO) in 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.Breast cancer is the most common malignancy in women in developed countries. In 2009 an estimated 194,280 new cases of breast cancer were diagnosed in the US[1]. Several studies have associated obesity and weight gain with breast cancer risk[2,3] and there is evidence that weight loss, as well as, decrease in fat consumption may lead to decreased risk for breast cancer[4,5]. Diabetes mellitus (DM) has also been associated with breast cancer risk [6]. This association between DM, obesity and breast cancer lead us to evaluate the role of genes, which have been found to be associated with diabetes and obesity, in predicting breast cancer risk.The fat mass and obesity (FTO) associated gene was recently found in several genome wide association studies (GWAS) to be associated with obesity and type II DM[7-11]. More specifically single nucleotide polymorphisms (SNPs) in intron 1 o