Fatty acid synthase (FAS) is the major enzyme of lipogenesis. It catalyzes the NADPH-dependent condensation of acetyl-CoA and malonyl-CoA to produce palmitic acid. Transcription of the FAS gene is controlled synergistically by the transcription factors ChREBP (carbohydrate response element-binding protein), which is induced by glucose, and SREBP-1 (sterol response element-binding protein-1), which is stimulated by insulin through the PI3K/Akt signal transduction pathway. We investigated whether the genetic variability of the genes encoding for ChREBP, SREBP and FAS (respectively, MLXIPL, SREBF1 and FASN) is related to breast cancer risk and body-mass index (BMI) by studying 1,294 breast cancer cases and 2,452 controls from the European Prospective Investigation on Cancer (EPIC). We resequenced the FAS gene and combined information of SNPs found by resequencing and SNPs from public databases. Using a tagging approach and selecting 20 SNPs, we covered all the common genetic variation of these genes. In this study we were not able to find any statistically significant association between the SNPs in the FAS, ChREBP and SREPB-1 genes and an increased risk of breast cancer overall and by subgroups of age, menopausal status, hormone replacement therapy (HRT) use or BMI. On the other hand, we found that two SNPs in FASN were associated with BMI.
|Autori:||Campa D;McKay J;Sinilnikova O;Huesing A;Vogel U;Hansen RD;Overvad K;Witt PM;Clavel-Chapelon F;Boutron-Ruault MC;Chajes V;Rohrmann S;Chang-Claude J;Boeing H;Fisher E;Trichopoulou A;Trichopoulos D;Palli D;Villarini A;Sacerdote C;Mattiello A;Tumino R;Peeters PH;van Gils CH;Bas Bueno-de-Mesquita H;Lund E;Chirlaque MD;Sala N;Suarez LR;Barricarte A;Dorronsoro M;Sanchez MJ;Lenner P;Hallmans G;Tsilidis K;Bingham S;Khaw KT;Gallo V;Norat T;Riboli E;Rinaldi S;Lenoir G;Tavtigian SV;Canzian F;Kaaks R|
|Titolo:||Genetic variation in genes of the fatty acid synthesis pathway and breast cancer risk.|
|Anno del prodotto:||2009|
|Digital Object Identifier (DOI):||10.1007/s10549-009-0347-8|
|Appare nelle tipologie:||1.1 Articolo in rivista|
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|Campa_FAS_Breast Cancer Research and Treatment_2009.pdf||Versione finale editoriale||Importato da Ugov Ricerca - Accesso privato/ristretto||Administrator Richiedi una copia|