Inflammatory cytokine gene polymorphisms, nonsteroidal anti-inflammatory drug use, and risk of adenoma polyp recurrence in the polyp prevention trial.
BACKGROUND
Pro- and anti-inflammatory cytokine genes may be important in the maintenance and progression of colorectal cancer. It is possible that single-nucleotide polymorphisms in inflammatory genes may play a role in chronic colonic inflammation and development of colorectal adenomas. Furthermore, common variants in cytokine genes may modify the anti-inflammatory effect of nonsteroidal anti-inflammatory drugs (NSAIDs) in the prevention of colorectal cancer.


METHODS
We examined the association between cytokine gene polymorphisms and risk of recurrent adenomas among 1,723 participants in the Polyp Prevention Trial. We used logistic regression to calculate odds ratios (OR) for the association between genotype, NSAID use, and risk of adenoma recurrence.


RESULTS
Cytokine gene polymorphisms were not statistically significantly associated with risk of adenoma recurrence in our study. We observed statistically significant interactions between NSAID use, IL-10 -1082 G>A genotype, and risk of adenoma recurrence (P = 0.01) and multiple adenoma recurrence (P = 0.01). Carriers of the IL-10 -1082 G>A variant allele who were non-NSAID users had a statistically significant decreased risk of multiple adenoma recurrence (OR, 0.43; 95% confidence interval, 0.24-0.77) as well as a nonsignificant 30% decreased risk of any adenoma recurrence. In contrast, NSAID users who were carriers of the IL-10 -1082 G>A variant allele were at an increased risk of any adenoma recurrence (OR, 1.55; 95% confidence interval, 1.00-2.43).


CONCLUSIONS
These findings suggest that individuals who are carriers of the IL-10 -1082 G>A variant allele may not benefit from the chemoprotective effect of NSAIDs on adenoma polyp recurrence.
Center for Cancer Research, National Cancer Institute, NIH, Department of Health and Human Services, Suite 702, 6116 Executive Boulevard, MSC 8235, Bethesda, MD 20892-8325, USA. sansburl@mail.nih.gov
Leah B
LB
Sansbury
Andrew W
AW
Bergen
Kay L
KL
Wanke
Binbing
B
Yu
Neil E
NE
Caporaso
Nilanjan
N
Chatterjee
Luke
L
Ratnasinghe
Arthur
A
Schatzkin
Teresa A
TA
Lehman
Aravind
A
Kalidindi
Ramakrishna
R
Modali
Elaine
E
Lanza
D018256:Adenomatous Polyps / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis; D001707:Biopsy, Needle; D003113:Colonoscopy; D015179:Colorectal Neoplasms / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D016001:Confidence Intervals; D016207:Cytokines / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D005260:Female; D014644:Genetic Variation; D006801:Humans; D007150:Immunohistochemistry; D015994:Incidence; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology / Q000517:prevention & control* / Q000628:therapy; D009367:Neoplasm Staging; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D015996:Survival Rate
D000894:Anti-Inflammatory Agents, Non-Steroidal; D014408:Biomarkers, Tumor; D016207:Cytokines