Common polymorphisms in 5-lipoxygenase and 12-lipoxygenase genes and the risk of incident, sporadic colorectal adenoma.
BACKGROUND
Lipoxygenases (LOX) are major enzymes that metabolize arachidonic acid to hydroxyl-eicosatetraenoic acids and leukotrienes, which have been implicated in inflammation and colorectal cancer risk. Polymorphisms in LOX genes may influence their function and/or expression and, thus, may modify the risk for colorectal adenoma. The authors investigated the associations of 3 polymorphisms (2 in 5-LOX, -1708 guanine-->adenine and 21 cytosine-->thymine; and 1 in 12-LOX, arginine 261 glutamine [Arg261Gln]) in LOX genes with the risk of colorectal adenoma and also explored possible interactions of these polymorphisms with several inflammation-pathway or arachidonic acid metabolism-pathway related factors with the risk of colorectal adenoma.


METHODS
By using data from a community-based, case-control study of incident, sporadic colorectal adenoma that included 162 cases and 211 controls, the authors constructed multiple logistic regression models to estimate the odds ratios (OR) and 95% confidence intervals (95% CI) of colorectal adenoma after adjusting for potential confounders.


RESULTS
Overall, there were no significant associations of the 2 5-LOX polymorphisms with the risk of colorectal adenoma. However, there was an inverse association between the Arg261Gln polymorphism in 12-LOX and colorectal adenoma (OR, 0.63; 95% CI, 0.40-1.00). A significant interaction also was observed between the 12-LOX polymorphism (Arg261Gln) and the use of nonsteroidal anti-inflammatory drugs (P(interaction) = .02).


CONCLUSIONS
The current results suggested that polymorphisms of LOX genes may act independently or with other factors to affect the risk of colorectal adenoma. Further studies will be needed to confirm these findings. Cancer 2007 (c) 2007 American Cancer Society.
Gong
Zhihong
Z
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Hebert
James R
JR
Bostick
Roberd M
RM
Deng
Zonglin
Z
Hurley
Thomas G
TG
Dixon
Dan A
DA
Nitcheva
Daniela
D
Xie
Dawen
D
D000236:Adenoma / Q000235:genetics*; D000328:Adult; D000368:Aged; D001092:Arachidonate 12-Lipoxygenase / Q000235:genetics*; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012307:Risk Factors
D001092:Arachidonate 12-Lipoxygenase; D001094:Arachidonate 5-Lipoxygenase