Ornithine decarboxylase-1 polymorphism, chemoprevention with eflornithine and sulindac, and outcomes among colorectal adenoma patients.
The ornithine decarboxylase-1 (ODC1) polymorphism at position +316 affects binding by transcriptional activators and repressors and modulates the risk of metachronous colorectal adenomas, particularly in association with aspirin use. We investigated the effects of ODC1 after treatment with difluoromethylornithine (eflornithine)/sulindac or placebo. Two hundred twenty-eight colorectal adenoma patients in a randomized phase III trial were genotyped for ODC1. We used Wilcoxon rank sums tests on non-normally distributed continuous variables across two genotype groups, χ(2) or Fisher exact test to assess the association between baseline categorical variables and genotype group, and log binomial regression for the primary (adenoma recurrence) and secondary outcomes (tissue polyamine response, cardiovascular toxicity, gastrointestinal toxicity, and ototoxicity). All statistical tests were two-sided. In binomial regression models with variables age, sex, race, aspirin use, treatment, and ODC1 genotype, treatment was the only statistically significant factor associated with differences in adenoma recurrence or tissue polyamine response. A statistically significant interaction was detected between ODC1 genotype and treatment with respect to adenoma recurrence (placebo group: GG, 50%, AA/GA: 34%; treatment group: GG, 11%, AA/GA, 21%; P(interaction) = .038). Excess ototoxicity was observed among ODC1 AA patients receiving treatment, but the interaction of genotype and treatment on ototoxicity was not statistically significant (P = .45).
Zell
Jason A
JA
Chao Family Comprehensive Cancer Center, Department of Epidemiology, University of California Irvine, 224 Irvine Hall, Irvine, CA 92697, USA. jzell@uci.edu
McLaren
Christine E
CE
Chen
Wen-Pin
WP
Thompson
Patricia A
PA
Gerner
Eugene W
EW
Meyskens
Frank L
FL
D000236:Adenoma / Q000201:enzymology / Q000235:genetics* / Q000517:prevention & control*; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000517:prevention & control*; D015986:Confounding Factors, Epidemiologic; D000518:Eflornithine / Q000008:administration & dosage; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D013467:Sulindac / Q000008:administration & dosage; D016896:Treatment Outcome
D004791:Enzyme Inhibitors; D011506:Proteins; C031017:ornithine decarboxylase antizyme; D013467:Sulindac; D000518:Eflornithine
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