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

Hoeft, Birgit; Linseisen, Jakob; Beckmann, Lars; Mueller-Decker, Karin; Canzian, Federico; Huesing, Anika; Kaaks, Rudolf; Vogel, Ulla; Jakobsen, Marianne U. and Overvad, Kim, et al. (2010) In Carcinogenesis 31(3). p.466-472
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 r(2) cutoff of 0.8 and a minor allele frequency of... (More)
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 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, 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. (Less)
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publication status
published
subject
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Carcinogenesis
volume
31
issue
3
pages
466 - 472
publisher
Oxford University Press
external identifiers
  • wos:000275245200020
  • scopus:77950886948
ISSN
0143-3334
DOI
10.1093/carcin/bgp325
language
English
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yes
id
4b3a8308-961c-4ff1-97d4-b0ccf1636b9c (old id 1589684)
date added to LUP
2010-04-20 09:55:38
date last changed
2018-05-29 10:29:03
@article{4b3a8308-961c-4ff1-97d4-b0ccf1636b9c,
  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 r(2) cutoff of 0.8 and a minor allele frequency of &gt; 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 &lt; 0.006) was found for PTGER2 GGG haplotype, whereas HPGD AGGAG and PLA2G3 CT haplotypes were significantly (P &lt; 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.},
  author       = {Hoeft, Birgit and Linseisen, Jakob and Beckmann, Lars and Mueller-Decker, Karin and Canzian, Federico and Huesing, Anika and Kaaks, Rudolf and Vogel, Ulla and Jakobsen, Marianne U. and Overvad, Kim and Hansen, Rikke D. and Knueppel, Sven and Boeing, Heiner and Trichopoulou, Antonia and Koumantaki, Yvoni and Trichopoulos, Dimitrios and Berrino, Franco and Palli, Domenico and Panico, Salvatore and Tumino, Rosario and Bueno-de-Mesquita, H. B. and van Duijnhoven, Franzel J. B. and van Gils, Carla H. and Peeters, Petra H. and Dumeaux, Vanessa and Lund, Eiliv and Huerta Castano, Jose M. and Munoz, Xavier and Rodriguez, Laudina and Barricarte, Aurelio and Manjer, Jonas and Jirström, Karin and Van Guelpen, Bethany and Hallmans, Goran and Spencer, Elizabeth A. and Crowe, Francesca L. and Khaw, Kay-Tee and Wareham, Nick and Morois, Sophie and Boutron-Ruault, Marie-Christine and Clavel-Chapelon, Francoise and Chajes, Veronique and Jenab, Mazda and Boffetta, Paolo and Vineis, Paolo and Mouw, Traci and Norat, Teresa and Riboli, Elio and Nieters, Alexandra},
  issn         = {0143-3334},
  language     = {eng},
  number       = {3},
  pages        = {466--472},
  publisher    = {Oxford University Press},
  series       = {Carcinogenesis},
  title        = {Polymorphisms in fatty acid metabolism-related genes are associated with colorectal cancer risk},
  url          = {http://dx.doi.org/10.1093/carcin/bgp325},
  volume       = {31},
  year         = {2010},
}