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01-12-2009 | Epidemiology

Genetic variation in genes of the fatty acid synthesis pathway and breast cancer risk

Authors: Daniele Campa, James McKay, Olga Sinilnikova, Anika Hüsing, Ulla Vogel, Rikke Dalgaard Hansen, Kim Overvad, Petra Mariann Witt, Françoise Clavel-Chapelon, Marie-Christine Boutron-Ruault, Veronique Chajes, Sabine Rohrmann, Jenny Chang-Claude, Heiner Boeing, Eva Fisher, Antonia Trichopoulou, Dimitrios Trichopoulos, Domenico Palli, Anna Villarini, Carlotta Sacerdote, Amalia Mattiello, Rosario Tumino, Petra H. M. Peeters, Carla H. van Gils, H. Bas Bueno-de-Mesquita, Eiliv Lund, María Dolores Chirlaque, Núria Sala, Laudina Rodriguez Suarez, Aurelio Barricarte, Miren Dorronsoro, Maria-José Sánchez, Per Lenner, Göran Hallmans, Kostas Tsilidis, Sheila Bingham, Kay-Tee Khaw, Valentina Gallo, Teresa Norat, Elio Riboli, Sabina Rinaldi, Gilbert Lenoir, Sean V. Tavtigian, Federico Canzian, Rudolf Kaaks

Published in: Breast Cancer Research and Treatment | Issue 3/2009

Abstract

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.

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Title: Genetic variation in genes of the fatty acid synthesis pathway and breast cancer risk
Authors: Daniele Campa
James McKay
Olga Sinilnikova
Anika Hüsing
Ulla Vogel
Rikke Dalgaard Hansen
Kim Overvad
Petra Mariann Witt
Françoise Clavel-Chapelon
Marie-Christine Boutron-Ruault
Veronique Chajes
Sabine Rohrmann
Jenny Chang-Claude
Heiner Boeing
Eva Fisher
Antonia Trichopoulou
Dimitrios Trichopoulos
Domenico Palli
Anna Villarini
Carlotta Sacerdote
Amalia Mattiello
Rosario Tumino
Petra H. M. Peeters
Carla H. van Gils
H. Bas Bueno-de-Mesquita
Eiliv Lund
María Dolores Chirlaque
Núria Sala
Laudina Rodriguez Suarez
Aurelio Barricarte
Miren Dorronsoro
Maria-José Sánchez
Per Lenner
Göran Hallmans
Kostas Tsilidis
Sheila Bingham
Kay-Tee Khaw
Valentina Gallo
Teresa Norat
Elio Riboli
Sabina Rinaldi
Gilbert Lenoir
Sean V. Tavtigian
Federico Canzian
Rudolf Kaaks
Publication date: 01-12-2009
Publisher: Springer US
Published in: Breast Cancer Research and Treatment / Issue 3/2009
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-009-0347-8

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