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Protective effect of Cox-2 allelic variants on risk of colorectal adenoma development in African Americans.

ABSTRACT: BACKGROUND:Recent evidence indicates that single nucleotide polymorphisms (SNPs) in the Cox-2 gene may modulate the risk of colorectal adenoma development. PATIENTS AND METHODS:We explored possible associations between Cox-2 polymorphisms and risk of adenoma development in an African American case-control study comprising 72 cases of advanced adenomas and 146 polyp-free controls. An exhaustive approach of genotyping 13 haplotype-tagging SNPs (ht SNPs) distributed over the entire COX-2 gene was used. RESULTS:Statistically significant inverse associations were observed between the heterozygous genotypes at the 5229 G>T polymorphism in intron 5 [odds ratio (OR)=0.42; confidence interval (CI)=0.19-0.92; p=0.03] and at the 10935 A>G polymorphism in the 3' flanking region downstream from the poly A signals (OR=0.39; CI=0.18-0.83;p=0.01) and the risk for colorectal adenoma development. CONCLUSION:The data from our pilot study suggest that allelic variants of the COX-2 gene significantly influence the risk of adenoma development in the African American population.

SUBMITTER: Ashktorab H

PROVIDER: S-EPMC6980310 | biostudies-literature | 2008 Sep-Oct

REPOSITORIES: biostudies-literature

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Protective effect of Cox-2 allelic variants on risk of colorectal adenoma development in African Americans.

Ashktorab Hassan H Tsang Shirley S Luke Brian B Sun Zhonghe Z Adam-Campbell Lucile L Kwagyan John J Poirier Richard R Akter Shahina S Akhgar Ahmad A Smoot Duane D Munroe David J DJ Ali Iqbal Unnisa IU

Anticancer research 20080901 5B

<h4>Background</h4>Recent evidence indicates that single nucleotide polymorphisms (SNPs) in the Cox-2 gene may modulate the risk of colorectal adenoma development.<h4>Patients and methods</h4>We explored possible associations between Cox-2 polymorphisms and risk of adenoma development in an African American case-control study comprising 72 cases of advanced adenomas and 146 polyp-free controls. An exhaustive approach of genotyping 13 haplotype-tagging SNPs (ht SNPs) distributed over the entire C ...[more]

PMID: 19031967

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Project description:BackgroundAfrican Americans (AAs) have higher colorectal cancer (CRC) incidence and mortality rate than Caucasian Americans (CAs). Recent studies suggest that immune responses within CRCs contribute to the disparities. If racially distinct immune signatures are present in the early phases of carcinogenesis, they could be used to develop interventions to prevent or slow disease.MethodsWe selected a convenience sample of 95 patients (48 CAs, 47 AAs) with preinvasive colorectal adenomas from the surgical pathology laboratory at the Medical University of South Carolina. Using immunofluorescent-conjugated antibodies on tissue slides from the lesions, we quantified specific immune cell populations: mast cells (CD117+), Th17 cells (CD4+RORC+), and NK cell ligand (MICA/B) and inflammatory cytokines, including IL-6, IL-17A, and IFN-γ. We compared the mean density counts (MDCs) and density rate ratios (RR) and 95% CI of immune markers between AAs to CAs using negative binomial regression analysis. We adjusted our models for age, sex, clinicopathologic characteristics (histology, location, dysplasia), and batch.ResultsWe observed no racial differences in age or sex at the baseline endoscopic exam. AAs compared to CAs had a higher prevalence of proximal adenomas (66% vs. 40%) and a lower prevalence of rectal adenomas (11% vs. 23%) (p =0.04) but no other differences in pathologic characteristics. In age, sex, and batch adjusted models, AAs vs. CAs had lower RRs for cells labeled with IFNγ (RR 0.50 (95% CI 0.32-0.81); p=0.004) and NK cell ligand (RR 0.67 (0.43-1.04); p=0.07). In models adjusted for age, sex, and clinicopathologic variables, AAs had reduced RRs relative to CAs for CD4 (p=0.02), NK cell ligands (p=0.01), Th17 (p=0.005), mast cells (p=0.04) and IFN-γ (p< 0.0001).ConclusionsOverall, the lower RRs in AAs vs. CAs suggests reduced effector response capacity and an immunosuppressive ('cold') tumor environment. Our results also highlight the importance of colonic location of adenoma in influencing these differences; the reduced immune responses in AAs relative to CAs may indicate impaired immune surveillance in early carcinogenesis. Future studies are needed to understand the role of risk factors (such as obesity) in influencing differences in immune responses by race.

Dataset Information

Protective effect of Cox-2 allelic variants on risk of colorectal adenoma development in African Americans.

Publications

Protective effect of Cox-2 allelic variants on risk of colorectal adenoma development in African Americans.

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