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

B. Hoeft, J. Linseisen, L. Beckmann, K. Muller-Decker, F. Canzian, A. Husing, R. Kaaks, Ulla Birgitte Vogel, Marianne Uhre Jakobsen, K. Overvad, R.D. Hansen, S. Knuppel, H. Boeing, A. Trichopoulou, Y. Koumantaki, D. Trichopoulos, F. Berrino, D. Palli, S. Panico, R. Tumino & 29 others H.B. Bueno-de-Mesquita, F.J.B. van Duijnhoven, C.H. van Gils, P.H. Peeters, V. Dumeaux, E. Lund, J.M.H. Castano, X. Munoz, L. Rodriguez, A. Barricarte, J. Manjer, K. Jirstrom, B. Van Guelpen, G. Hallmans, E.A. Spencer, F.L. Crowe, K.T. Khaw, N. Wareham, S. Morois, M.C. Boutron-Ruault, F. Clavel-Chapelon, V. Chajes, M. Jenab, P. Boffetta, P. Vineis, T. Mouw, T. Norat, E. Riboli, A. Nieters

Research output: Contribution to journalJournal articleResearchpeer-review

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 > 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
JournalCarcinogenesis
Volume31
Issue number3
Pages (from-to)466-472
ISSN0143-3334
DOIs
Publication statusPublished - 2010

Cite this

Hoeft, B., Linseisen, J., Beckmann, L., Muller-Decker, K., Canzian, F., Husing, 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
Hoeft, B. ; Linseisen, J. ; Beckmann, L. ; Muller-Decker, K. ; Canzian, F. ; Husing, A. ; Kaaks, R. ; Vogel, Ulla Birgitte ; Jakobsen, Marianne Uhre ; Overvad, K. ; Hansen, R.D. ; Knuppel, S. ; Boeing, H. ; Trichopoulou, A. ; Koumantaki, Y. ; Trichopoulos, D. ; Berrino, F. ; Palli, D. ; Panico, S. ; Tumino, R. ; Bueno-de-Mesquita, H.B. ; van Duijnhoven, F.J.B. ; van Gils, C.H. ; Peeters, P.H. ; Dumeaux, V. ; Lund, E. ; Castano, J.M.H. ; Munoz, X. ; Rodriguez, L. ; Barricarte, A. ; Manjer, J. ; Jirstrom, K. ; Van Guelpen, B. ; Hallmans, G. ; Spencer, E.A. ; Crowe, F.L. ; Khaw, K.T. ; Wareham, N. ; Morois, S. ; Boutron-Ruault, M.C. ; Clavel-Chapelon, F. ; Chajes, V. ; Jenab, M. ; Boffetta, P. ; Vineis, P. ; Mouw, T. ; Norat, T. ; Riboli, E. ; Nieters, A. / 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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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 > 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.",
author = "B. Hoeft and J. Linseisen and L. Beckmann and K. Muller-Decker and F. Canzian and A. Husing and R. Kaaks and Vogel, {Ulla Birgitte} and Jakobsen, {Marianne Uhre} and K. Overvad and R.D. Hansen and S. Knuppel and H. Boeing and A. Trichopoulou and Y. Koumantaki and D. Trichopoulos and F. Berrino and D. Palli and S. Panico and R. Tumino and H.B. Bueno-de-Mesquita and {van Duijnhoven}, F.J.B. and {van Gils}, C.H. and P.H. Peeters and V. Dumeaux and E. Lund and J.M.H. Castano and X. Munoz and L. Rodriguez and A. Barricarte and J. Manjer and K. Jirstrom and {Van Guelpen}, B. and G. Hallmans and E.A. Spencer and F.L. Crowe and K.T. Khaw and N. Wareham and S. Morois and M.C. Boutron-Ruault and F. Clavel-Chapelon and V. Chajes and M. Jenab and P. Boffetta and P. Vineis and T. Mouw and T. Norat and E. Riboli and A. Nieters",
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language = "English",
volume = "31",
pages = "466--472",
journal = "Carcinogenesis",
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Hoeft, B, Linseisen, J, Beckmann, L, Muller-Decker, K, Canzian, F, Husing, A, Kaaks, R, Vogel, UB, Jakobsen, MU, Overvad, K, Hansen, RD, Knuppel, S, Boeing, H, Trichopoulou, A, Koumantaki, Y, Trichopoulos, D, Berrino, F, Palli, D, Panico, S, Tumino, R, Bueno-de-Mesquita, HB, van Duijnhoven, FJB, van Gils, CH, Peeters, PH, Dumeaux, V, Lund, E, Castano, JMH, Munoz, X, Rodriguez, L, Barricarte, A, Manjer, J, Jirstrom, 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

Polymorphisms in fatty acid metabolism-related genes are associated with colorectal cancer risk. / Hoeft, B.; Linseisen, J.; Beckmann, L.; Muller-Decker, K.; Canzian, F.; Husing, A.; Kaaks, R.; Vogel, Ulla Birgitte; Jakobsen, Marianne Uhre; Overvad, K.; Hansen, R.D.; Knuppel, S.; Boeing, H.; Trichopoulou, A.; Koumantaki, Y.; Trichopoulos, D.; Berrino, F.; Palli, D.; Panico, S.; Tumino, R.; Bueno-de-Mesquita, H.B.; van Duijnhoven, F.J.B.; van Gils, C.H.; Peeters, P.H.; Dumeaux, V.; Lund, E.; Castano, J.M.H.; Munoz, X.; Rodriguez, L.; Barricarte, A.; Manjer, J.; Jirstrom, K.; Van Guelpen, B.; Hallmans, G.; Spencer, E.A.; Crowe, F.L.; Khaw, K.T.; Wareham, N.; Morois, S.; Boutron-Ruault, M.C.; Clavel-Chapelon, F.; Chajes, V.; Jenab, M.; Boffetta, P.; Vineis, P.; Mouw, T.; Norat, T.; Riboli, E.; Nieters, A.

In: Carcinogenesis, Vol. 31, No. 3, 2010, p. 466-472.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Polymorphisms in fatty acid metabolism-related genes are associated with colorectal cancer risk

AU - Hoeft, B.

AU - Linseisen, J.

AU - Beckmann, L.

AU - Muller-Decker, K.

AU - Canzian, F.

AU - Husing, A.

AU - Kaaks, R.

AU - Vogel, Ulla Birgitte

AU - Jakobsen, Marianne Uhre

AU - Overvad, K.

AU - Hansen, R.D.

AU - Knuppel, S.

AU - Boeing, H.

AU - Trichopoulou, A.

AU - Koumantaki, Y.

AU - Trichopoulos, D.

AU - Berrino, F.

AU - Palli, D.

AU - Panico, S.

AU - Tumino, R.

AU - Bueno-de-Mesquita, H.B.

AU - van Duijnhoven, F.J.B.

AU - van Gils, C.H.

AU - Peeters, P.H.

AU - Dumeaux, V.

AU - Lund, E.

AU - Castano, J.M.H.

AU - Munoz, X.

AU - Rodriguez, L.

AU - Barricarte, A.

AU - Manjer, J.

AU - Jirstrom, K.

AU - Van Guelpen, B.

AU - Hallmans, G.

AU - Spencer, E.A.

AU - Crowe, F.L.

AU - Khaw, K.T.

AU - Wareham, N.

AU - Morois, S.

AU - Boutron-Ruault, M.C.

AU - Clavel-Chapelon, F.

AU - Chajes, V.

AU - Jenab, M.

AU - Boffetta, P.

AU - Vineis, P.

AU - Mouw, T.

AU - Norat, T.

AU - Riboli, E.

AU - Nieters, A.

PY - 2010

Y1 - 2010

N2 - 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.

AB - 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.

U2 - 10.1093/carcin/bgp325

DO - 10.1093/carcin/bgp325

M3 - Journal article

VL - 31

SP - 466

EP - 472

JO - Carcinogenesis

JF - Carcinogenesis

SN - 0143-3334

IS - 3

ER -

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