The role of the fat mass and obesity associated gene (FTO) in breast cancer risk

BMC Medical Genetics

Research Article

Maureen Sadim¹  Virginia Kaklamani²  Surbhi Agarwal³  Sarah Tofilon³  Kalliopi Siziopikou⁴  Christos Mantzoros⁵  Boris Pasche⁶  Yanfei Xu⁷  Nengjun Yi⁸  Kui Zhang⁹ 

[1] Cancer Genetics Program, Division of Hematology/Oncology, Department of Medicine and Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, 303 E Superior Street, IL60611, Chicago, USA;Cancer Genetics Program, Division of Hematology/Oncology, Department of Medicine and Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, 676 N St Clair st suite 850, 60611, Chicago, IL, USA;Department of Medicine and Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, 303 E Superior Street, 60611, Chicago, IL, USA;Department of Pathology, Northwestern Memorial Hospital, 675 N St Clair st, 60611, Chicago, IL, USA;Division of Endocrinology and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center (BIDMC), Harvard Medical School, 330 Brookline Avenue FD-876, 02215, Boston, MA, USA;Division of Hematology/Oncology and Comprehensive Cancer Center, University of Alabama, 1802 6th Avenue South, NP 2566, AL35294, Birmingham, USA;Division of Hematology/Oncology, Department of Medicine and Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, 303 E Superior Street, 60611, Chicago, IL, USA;Section on Statistical Genetics, Department of Biostatistics, School of Public Health, University of Alabama at Birmingham, 1665 University Blvd, Ryals Bldg. 317F, 35294, Birmingham, AL, USA;Section on Statistical Genetics, Department of Biostatistics, School of Public Health, University of Alabama at Birmingham, 1665 University Blvd, Ryals Bldg. 327H, 35294, Birmingham, AL, USA;

关键词: Breast Cancer;    Progesterone Receptor;    Breast Cancer Risk;    Epistatic Interaction;    Dominance Effect;   

DOI  :  10.1186/1471-2350-12-52

 received in 2011-01-31, accepted in 2011-04-13,  发布年份 2011

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY   
© Kaklamani et al; licensee BioMed Central Ltd. 2011