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

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 SacerdoteAmalia 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

Research output: Contribution to journalArticleAcademicpeer-review

18 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)565-574
Number of pages10
JournalBreast Cancer Research and Treatment
Volume118
Issue number3
DOIs
Publication statusPublished - Dec-2009
Externally publishedYes

Keywords

  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics
  • Body Mass Index
  • Breast Neoplasms/genetics
  • Fatty Acid Synthase, Type I/genetics
  • Female
  • Genetic Predisposition to Disease
  • Genetic Variation
  • Humans
  • Obesity/genetics
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide
  • Risk Factors
  • Sterol Regulatory Element Binding Protein 1/genetics

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