Polymorphisms in fatty acid metabolism-related genes are associated with colorectal cancer risk

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  • Birgit Hoeft, Denmark
  • Jakob Linseisen, Denmark
  • Lars Beckmann, Denmark
  • Karin Müller-Decker, Denmark
  • Federico Canzian, Denmark
  • Anika Hüsing, Denmark
  • Rudolf Kaaks, Denmark
  • Ulla Vogel, Denmark
  • Marianne Uhre Jakobsen, Denmark
  • Kim Overvad
  • Rikke Dalgaard Hansen, Denmark
  • Sven Knüppel, Denmark
  • Heiner Boeing, Denmark
  • Antonia Trichopoulou, Denmark
  • Koumantaki Yvoni, Denmark
  • Dimitrios Trichopoulos, Denmark
  • Franco Berrino, Denmark
  • Domenico Palli, Denmark
  • Salvatore Panico, Denmark
  • Rosario Tumino, Denmark
  • H Bas Bueno-de-Mesquita, Denmark
  • Fränzel J B van Duijnhoven, Denmark
  • Carla H van Gils, Denmark
  • Petra H Peeters, Denmark
  • Vanessa Dumeaux, Denmark
  • Eiliv Lund, Denmark
  • José M Huerta Castaño, Denmark
  • Xavier Muñoz, Denmark
  • Laudina Rodriguez, Denmark
  • Aurelio Barricarte, Denmark
  • Jonas Manjer, Denmark
  • Karin Jirström, Denmark
  • Bethany Van Guelpen, Denmark
  • Göran Hallmans, Denmark
  • Elizabeth A Spencer, Denmark
  • Francesca L Crowe, Denmark
  • Kay-Tee Khaw, Denmark
  • Nick Wareham, Denmark
  • Sophie Morois, Denmark
  • Marie-Christine Boutron-Ruault, Denmark
  • Françoise Clavel-Chapelon, Denmark
  • Veronique Chajes, Denmark
  • Mazda Jenab, Denmark
  • Paolo Boffetta, Denmark
  • Paolo Vineis, Denmark
  • Traci Mouw, Denmark
  • Teresa Norat, Denmark
  • Elio Riboli, Denmark
  • Alexandra Nieters, Denmark
  • Institute of Epidemiology and Social Medicine
  • Klinisk Epidemiologisk Afdeling, Aalborg
Colorectal cancer is the third most common malignant tumor and the fourth-leading cause of cancer death worldwide. The crucial role of fatty acids for a number of important biological processes suggests a more in depth analysis of inter-individual differences in fatty acid metabolizing genes as contributing factor to colon carcinogenesis. We examined the association between genetic variability in 43 fatty acid metabolism-related genes and colorectal risk in 1225 CRC cases and 2032 controls participating in the European Prospective Investigation into Cancer and Nutrition study. 392 single nucleotide polymorphisms were selected using pairwise tagging with an r(2) cutoff of 0.8 and a minor allele frequency of >5%. Conditional logistic regression models were used to estimate odds ratios and corresponding 95% confidence intervals. Haplotype analysis was performed using a generalized linear model framework. On the genotype level, HPGD, PLA2G6, and TRPV3 were associated with higher risk for colorectal cancer, while PTGER2 was associated with lower colorectal cancer risk. A significant inverse association (p < 0.006) was found for PTGER2 GGG haplotype while HPGD AGGAG and PLA2G3 CT haplotypes were significantly (p < 0.001 and p = 0.003, respectively) associated with higher risk of colorectal cancer. Based on these data we present for the first time the association of HPGD variants with colorectal cancer risk. Our results support the key role of prostanoid signaling in colon carcinogenesis and suggest a relevance of genetic variation in fatty acid metabolism-related genes and colorectal cancer risk.
Original languageEnglish
Pages (from-to)466-472
Publication statusPublished - 2010

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