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

Birgit Hoeft, Jakob Linseisen, Lars Beckmann, Karin Müller-Decker, Federico Canzian, Anika Hüsing, Rudolf Kaaks, Ulla Vogel, Marianne U. Jakobsen, Kim Overvad, Rikke D. Hansen, Sven Knüppel, Heiner Boeing, Antonia Trichopoulou, Yvoni Koumantaki, Dimitrios Trichopoulos, Franco Berrino, Domenico Palli, Salvatore Panico, Rosario Tumino & 29 others H. B. Buenode-Mesquita, Fränzel J B van Duijnhoven, Carla H. van Gils, Petra H. Peeters, Vanessa Dumeaux, Eiliv Lund, José M. Huerta Castaño, Xavier Muñoz, Laudina Rodriguez, Aurelio Barricarte, Jonas Manjer, Karin Jirström, Bethany van Guelpen, Göran Hallmans, Elizabeth A. Spencer, Francesca L. Crowe, Kay Tee Khaw, Nick Wareham, Sophie Morois, Marie Christine Boutron-Ruault, Françxoise Clavel-Chapelon, Veronique Chajes, Mazda Jenab, Paolo Boffetta, Paolo Vineis, Traci Mouw, Teresa Norat, Elio Riboli, Alexandra Nieters

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Colorectal cancer (CRC) 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. Three hundred and ninety two single-nucleotide polymorphisms were selected using pairwise tagging with an r2 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, hydroxyprostaglandin dehydrogenase 15-(NAD) (HPGD), phospholipase A2 group VI (PLA2G6) and transient receptor potential vanilloid 3 were associated with higher risk for CRC, whereas prostaglandin E receptor 2 (PTGER2) was associated with lower CRC risk. A significant inverse association (P <0.006) was found for PTGER2 GGG haplotype, whereas HPGD AGGAG and PLA2G3 CT haplotypes were significantly (P <0.001 and P = 0.003, respectively) associated with higher risk of CRC. Based on these data, we present for the first time the association of HPGD variants with CRC 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 CRC risk.

Original languageEnglish
Pages (from-to)466-472
Number of pages7
JournalCarcinogenesis
Volume31
Issue number3
DOIs
Publication statusPublished - Mar 2010

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Colorectal Neoplasms
Fatty Acids
Receptors, Prostaglandin E, EP2 Subtype
Genes
Haplotypes
15-hydroxyprostaglandin dehydrogenase
Group VI Phospholipases A2
Colon
Carcinogenesis
Logistic Models
Biological Phenomena
TRPV Cation Channels
Neoplasms
Gene Frequency
Individuality
Prostaglandins
Single Nucleotide Polymorphism
Cause of Death
Linear Models
Odds Ratio

ASJC Scopus subject areas

  • Cancer Research

Cite this

Hoeft, B., Linseisen, J., Beckmann, L., Müller-Decker, K., Canzian, F., Hüsing, A., ... Nieters, A. (2010). Polymorphisms in fatty acid metabolism-related genes are associated with colorectal cancer risk. Carcinogenesis, 31(3), 466-472. https://doi.org/10.1093/carcin/bgp325

Polymorphisms in fatty acid metabolism-related genes are associated with colorectal cancer risk. / Hoeft, Birgit; Linseisen, Jakob; Beckmann, Lars; Müller-Decker, Karin; Canzian, Federico; Hüsing, Anika; Kaaks, Rudolf; Vogel, Ulla; Jakobsen, Marianne U.; Overvad, Kim; Hansen, Rikke D.; Knüppel, Sven; Boeing, Heiner; Trichopoulou, Antonia; Koumantaki, Yvoni; Trichopoulos, Dimitrios; Berrino, Franco; Palli, Domenico; Panico, Salvatore; Tumino, Rosario; Buenode-Mesquita, H. B.; van Duijnhoven, Fränzel J B; van Gils, Carla H.; Peeters, Petra H.; Dumeaux, Vanessa; Lund, Eiliv; Huerta Castaño, José M.; Muñoz, Xavier; Rodriguez, Laudina; Barricarte, Aurelio; Manjer, Jonas; Jirström, Karin; van Guelpen, Bethany; Hallmans, Göran; Spencer, Elizabeth A.; Crowe, Francesca L.; Khaw, Kay Tee; Wareham, Nick; Morois, Sophie; Boutron-Ruault, Marie Christine; Clavel-Chapelon, Françxoise; Chajes, Veronique; Jenab, Mazda; Boffetta, Paolo; Vineis, Paolo; Mouw, Traci; Norat, Teresa; Riboli, Elio; Nieters, Alexandra.

In: Carcinogenesis, Vol. 31, No. 3, 03.2010, p. 466-472.

Research output: Contribution to journalArticle

Hoeft, B, Linseisen, J, Beckmann, L, Müller-Decker, K, Canzian, F, Hüsing, A, Kaaks, R, Vogel, U, Jakobsen, MU, Overvad, K, Hansen, RD, Knüppel, S, Boeing, H, Trichopoulou, A, Koumantaki, Y, Trichopoulos, D, Berrino, F, Palli, D, Panico, S, Tumino, R, Buenode-Mesquita, HB, van Duijnhoven, FJB, van Gils, CH, Peeters, PH, Dumeaux, V, Lund, E, Huerta Castaño, JM, Muñoz, X, Rodriguez, L, Barricarte, A, Manjer, J, Jirström, K, van Guelpen, B, Hallmans, G, Spencer, EA, Crowe, FL, Khaw, KT, Wareham, N, Morois, S, Boutron-Ruault, MC, Clavel-Chapelon, F, Chajes, V, Jenab, M, Boffetta, P, Vineis, P, Mouw, T, Norat, T, Riboli, E & Nieters, A 2010, 'Polymorphisms in fatty acid metabolism-related genes are associated with colorectal cancer risk', Carcinogenesis, vol. 31, no. 3, pp. 466-472. https://doi.org/10.1093/carcin/bgp325
Hoeft B, Linseisen J, Beckmann L, Müller-Decker K, Canzian F, Hüsing A et al. Polymorphisms in fatty acid metabolism-related genes are associated with colorectal cancer risk. Carcinogenesis. 2010 Mar;31(3):466-472. https://doi.org/10.1093/carcin/bgp325
Hoeft, Birgit ; Linseisen, Jakob ; Beckmann, Lars ; Müller-Decker, Karin ; Canzian, Federico ; Hüsing, Anika ; Kaaks, Rudolf ; Vogel, Ulla ; Jakobsen, Marianne U. ; Overvad, Kim ; Hansen, Rikke D. ; Knüppel, Sven ; Boeing, Heiner ; Trichopoulou, Antonia ; Koumantaki, Yvoni ; Trichopoulos, Dimitrios ; Berrino, Franco ; Palli, Domenico ; Panico, Salvatore ; Tumino, Rosario ; Buenode-Mesquita, H. B. ; van Duijnhoven, Fränzel J B ; van Gils, Carla H. ; Peeters, Petra H. ; Dumeaux, Vanessa ; Lund, Eiliv ; Huerta Castaño, José M. ; Muñoz, Xavier ; Rodriguez, Laudina ; Barricarte, Aurelio ; Manjer, Jonas ; Jirström, Karin ; van Guelpen, Bethany ; Hallmans, Göran ; Spencer, Elizabeth A. ; Crowe, Francesca L. ; Khaw, Kay Tee ; Wareham, Nick ; Morois, Sophie ; Boutron-Ruault, Marie Christine ; Clavel-Chapelon, Françxoise ; Chajes, Veronique ; Jenab, Mazda ; Boffetta, Paolo ; Vineis, Paolo ; Mouw, Traci ; Norat, Teresa ; Riboli, Elio ; Nieters, Alexandra. / Polymorphisms in fatty acid metabolism-related genes are associated with colorectal cancer risk. In: Carcinogenesis. 2010 ; Vol. 31, No. 3. pp. 466-472.
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AU - Kaaks, Rudolf

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AU - Boffetta, Paolo

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AU - Norat, Teresa

AU - Riboli, Elio

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