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

Publisher: Irl Press At Oxford University Press Country of Publication: England NLM ID: 8008055 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1460-2180 (Electronic) Linking ISSN: 01433334 NLM ISO Abbreviation: Carcinogenesis Subsets: MEDLINE

Publication: Oxford : Irl Press At Oxford University Press
Original Publication: [New York, IRL Press]

Genetic Association Studies* ; Polymorphism, Single Nucleotide*; Adenocarcinoma/*genetics ; Colorectal Neoplasms/*genetics ; Fatty Acids/*metabolism; Adenocarcinoma/epidemiology ; Adenocarcinoma/metabolism ; Alleles ; Case-Control Studies ; Cohort Studies ; Colorectal Neoplasms/epidemiology ; Colorectal Neoplasms/metabolism ; Europe/epidemiology ; Female ; Genotype ; Group III Phospholipases A2/genetics ; Group VI Phospholipases A2/genetics ; Haplotypes ; Humans ; Hydroxyprostaglandin Dehydrogenases/genetics ; Male ; Neoplasm Proteins/genetics ; Receptors, Prostaglandin E/genetics ; Receptors, Prostaglandin E, EP2 Subtype ; Smoking/epidemiology ; TRPV Cation Channels/genetics

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.

United Kingdom WT_ Wellcome Trust; United Kingdom BHF_ British Heart Foundation; United Kingdom DH_ Department of Health; MC_U106179471 United Kingdom MRC_ Medical Research Council; G0401527 United Kingdom MRC_ Medical Research Council; United Kingdom CRUK_ Cancer Research UK

0 (Fatty Acids)
0 (Neoplasm Proteins)
0 (PTGER2 protein, human)
0 (Receptors, Prostaglandin E)
0 (Receptors, Prostaglandin E, EP2 Subtype)
0 (TRPV Cation Channels)
0 (TRPV3 protein, human)
EC 1.1.1.- (Hydroxyprostaglandin Dehydrogenases)
EC 1.1.1.141 (15-hydroxyprostaglandin dehydrogenase)
EC 3.1.1.4 (Group III Phospholipases A2)
EC 3.1.1.4 (Group VI Phospholipases A2)
EC 3.1.1.4 (PLA2G3 protein, human)
EC 3.1.1.4 (PLA2G6 protein, human)

Date Created: 20100101 Date Completed: 20100414 Latest Revision: 20211028

20221213

10.1093/carcin/bgp325

20042636