Abstract
BackgroundObesity 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.MethodsWe 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.ResultsWe 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.ConclusionIn 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.
Highlights
Obesity has been shown to increase breast cancer risk
We tested for Hardy-Weinberg equilibrium (HWE) for each single nucleotide polymorphism (SNP) among controls
We performed staining for fatty acid binding protein 4 (FABP4), an adipocyte marker, and found that seven of 18 (38.8%) breast tumors stained positive and three of 20 (15%) normal breast epithelium stained positive, whereas all adipose tissue stained positive for FABP4. In this clinic-based case-control study we found that SNPs located in intron 1 of fat mass and obesity (FTO) are associated with breast cancer risk
Summary
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. Diabetes mellitus (DM) has 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. Its role remains essentially unclear, it seems that FTO encodes a 2-oxoglutarate-dependent nucleic acid demethylase [12]. It is localized in the nucleus and is abundant in the brain [12]. FTO has been shown to be expressed in other tissue as well including the pancreas, skeletal muscle and white adipose tissue its expression in these tissues is significantly lower than its expression in the hypothalamus and the cerebellum [12]
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