Περίληψη:
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.
Συγγραφείς:
Hoeft, Birgit
Linseisen, Jakob
Beckmann, Lars and
Mueller-Decker, Karin
Canzian, Federico
Huesing, Anika and
Kaaks, Rudolf
Vogel, Ulla
Jakobsen, Marianne U.
Overvad, Kim
and Hansen, Rikke D.
Knueppel, Sven
Boeing, Heiner and
Trichopoulou, Antonia
Koumantaki, Yvoni
Trichopoulos, Dimitrios
and Berrino, Franco
Palli, Domenico
Panico, Salvatore and
Tumino, Rosario
Bueno-de-Mesquita, H. B.
van Duijnhoven, Franzel
J. B.
van Gils, Carla H.
Peeters, Petra H.
Dumeaux, Vanessa
and Lund, Eiliv
Huerta Castano, Jose M.
Munoz, Xavier and
Rodriguez, Laudina
Barricarte, Aurelio
Manjer, Jonas and
Jirstrom, Karin
Van Guelpen, Bethany
Hallmans, Goran and
Spencer, Elizabeth A.
Crowe, Francesca L.
Khaw, Kay-Tee and
Wareham, Nick
Morois, Sophie
Boutron-Ruault, Marie-Christine and
Clavel-Chapelon, Francoise
Chajes, Veronique
Jenab, Mazda and
Boffetta, Paolo
Vineis, Paolo
Mouw, Traci
Norat, Teresa and
Riboli, Elio
Nieters, Alexandra
