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Cyclooxygenase-2 gene polymorphisms and the risk of colorectal cancer: A population-based study.

ABSTRACT: The aim of the present study was to determine the association between polymorphisms in the cyclooxygenase-2 (COX-2) gene promoter region, rs20417 G/C and rs2745557 G/A, and the susceptibility to colorectal cancer (CRC) in a Han Chinese population in Shaanxi, China. Polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) were used to detect the polymorphisms of COX-2, rs20417 G/C and rs2745557 G/A, in 300 patients with CRC and 300 healthy individuals in the present case-control study. The results revealed that for the COX-2 rs20417 G/C polymorphism, the GC+CC allele frequency was 80% in CRC patients and 71% in healthy controls [odds ratio (OR)=1.63; 95% confidence interval (CI), 1.12-2.38; P=0.01]. For the COX-2 rs2745557 G/A polymorphism, the GA+AA allele frequency was 84% in CRC patients and 73% in healthy controls (OR=1.94; 95% CI, 1.30-2.90; P<0.01). In addition, among individuals with a smoking history, drinking history or family history of CRC, those who were COX-2 rs20417 (GC+CC) or COX-2 rs2745557 (GA+AA) carriers had a significantly increased risk of developing CRC compared with that of GG genotype carriers (P<0.05). Furthermore, the allelic frequencies of COX-2 rs20417 G/C and rs2745557 G/A in patients with lymph node metastasis in stage III/IV of CRC were significantly different from those of COX-2 rs20417 G/C and rs2745557 G/A in patients without lymph node metastasis in stage I/II (P<0.05). In conclusion, the results of the present study revealed that COX-2 rs20417 C allele carriers and rs2745557 A allele carriers have a significantly increased risk of CRC compared with GG genotype carriers; in addition, the frequencies of these alleles were demonstrated to be associated with lymph node metastasis and CRC progression.

SUBMITTER: Li H

PROVIDER: S-EPMC4533694 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Cyclooxygenase-2 gene polymorphisms and the risk of colorectal cancer: A population-based study.

Li Hongxia H Guo Qinyue Q Zhou Bo B He Shuixiang S

Oncology letters 20150709 3

The aim of the present study was to determine the association between polymorphisms in the cyclooxygenase-2 (COX-2) gene promoter region, rs20417 G/C and rs2745557 G/A, and the susceptibility to colorectal cancer (CRC) in a Han Chinese population in Shaanxi, China. Polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) were used to detect the polymorphisms of COX-2, rs20417 G/C and rs2745557 G/A, in 300 patients with CRC and 300 healthy individuals in the present case- ...[more]

PMID: 26622766

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Project description:BACKGROUND: Cyclooxygenase-2 (COX-2) is up-regulated in several types of cancer, and it is hypothesized that COX-2 expression may be genetically influenced. Here, we evaluate the association between single-nucleotide polymorphisms (SNPs) in the COX-2 gene (PTGS2) and the occurrence of breast cancer among Brazilian women. METHODS: The study was conducted prospectively in two steps: First, we screened the promoter region and three fragments of the 3'-untranslated region of PTGS2 from 67 healthy Brazilians to identify SNPs and to select those with a minor allele frequency (MAF) of at least 0.10. The MAF of these selected SNPs was further characterized in 402 healthy volunteers to evaluate potential differences related to heterogeneous racial admixture and to estimate the existence of linkage disequilibrium among the SNPs. The second step was a case-control study with 318 patients and 273 controls designed to evaluate PTGS2 genotype- or haplotype-associated risk of breast cancer. RESULTS: The screening analysis indicated nine SNPs with the following MAFs: rs689465 (0.22), rs689466 (0.15), rs20415 (0.007), rs20417 (0.32), rs20419 (0.015), rs5270 (0.02), rs20424 (0.007), rs5275 (0.22) and rs4648298 (0.01). The SNPs rs689465, rs689466, rs20417 and rs5275 were further studied: Their genotypic distributions followed Hardy-Weinberg equilibrium and the MAFs were not affected by gender or skin color. Strong linkage disequilibrium was detected for rs689465, rs20417 and rs5275 in the three possible pairwise combinations. In the case-control study, there was a significant increase of rs5275TC heterozygotes in cases compared to controls (OR = 1.44, 95% CI = 1.01-2.06; P = 0.043), and the haplotype formed by rs689465G, rs689466A, rs20417G and rs5275C was only detected in cases. The apparent association with breast cancer was not confirmed for rs5275CC homozygotes or for the most frequent rs5275C-containing haplotypes. CONCLUSIONS: Our results indicate no strong association between the four most frequent PTGS2 SNPs and the risk of breast cancer.

Dataset Information

Cyclooxygenase-2 gene polymorphisms and the risk of colorectal cancer: A population-based study.

Publications

Cyclooxygenase-2 gene polymorphisms and the risk of colorectal cancer: A population-based study.

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