Polymorphic variants in PTGS2 and prostate cancer risk: results from two large nested case-control studies

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20852, USA.
Carcinogenesis (Impact Factor: 5.27). 03/2008; 29(3):568-72. DOI: 10.1093/carcin/bgm253
Source: PubMed

ABSTRACT Chronic inflammation has been hypothesized to increase prostate cancer risk. Prostaglandin-endoperoxide synthase 2 (PTGS2) encodes the proinflammatory cyclooxygenase 2 enzyme believed to be the rate-limiting step in the synthesis of prostaglandins, important mediators of inflammation. We investigated associations between PTGS2 polymorphisms and prostate cancer risk among 2321 prostate cancer cases and 2560 controls in two large case-control studies nested within the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial and the Cancer Prevention Study II Nutrition Cohort. Five single nucleotide polymorphisms (SNPs) (rs5277, rs20432, rs4648276, rs5275 and rs689470) were examined in SNP and haplotype analyses (five SNPs in PLCO and four SNPs in the Nutrition Cohort). In PLCO, the Ex10 +837 T>C marker (rs5275) was initially associated with prostate cancer risk (P-trend = 0.02) but became non-significant after adjustment for multiple comparisons (P = 0.08); this SNP showed no association with prostate cancer risk in the Nutrition Cohort (P-trend = 0.54) or in an analysis pooling the two cohorts (P-trend = 0.20). No other SNP was associated with prostate cancer risk in PLCO or the Nutrition Cohort individually or combined. Haplotype analyses suggested an association between PTGS2 variants in PLCO alone (global P = 0.007), but not in the Nutrition Cohort (global P = 0.78) or pooled analysis (global P = 0.18). In conclusion, despite the potential importance of inflammation in prostate carcinogenesis, results from our large study of five PTGS2 SNPs does not support a strong association between PTGS2 variants and prostate cancer risk in non-Hispanic white men.

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    ABSTRACT: The aim of the present study was to determine whether the interleukin-6 (IL-6) (-174 G/C) gene polymorphism correlates with prostate cancer. A meta-analysis based on former studies was conducted and the results suggest that there was no significant association between IL-6 (-174 G/C) polymorphism and the prostate cancer risk. However, a recent study published in January 2014 showed that the GG genotype may be associated with an increased risk of prostate cancer in Caucasian subjects, whereas the CC genotype was associated with an increased risk in the African-American subjects, which was inconsistent with former studies. Databases, including PubMed, Embase, Web of Science, the Cochrane Library, Chinese Biomedical Literature Database and Wanfang database, were searched between January 1994 and March 2014 to determine the eligible IL-6 (-174 G/C) polymorphism studies and the susceptibility of the prostate cancer risk. A total of 11 studies with 10,745 cases and 13,473 controls fulfilled the inclusion criteria subsequent to assessment by two investigators. The pooled odds ratio (OR) with 95% confidence interval (95% CI) was calculated to examine the associations, and subgroup analyses were performed according to the ethnicity. Overall, no significant association was found between the IL-6 (-174 G/C) polymorphism and prostate cancer risk, whereas the subgroup analysis suggested that the association between the IL-6 (-174 G/C) polymorphism and prostate cancer was slightly significant under the homozygote (CC vs. GG: OR, 3.43; 95% CI, 1.01-11.71; P=0.049) and recessive models (CC vs.
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    ABSTRACT: Background: The prostaglandin-endoperoxide synthase 2 [PTGS2, commonly known as cyclooxygenase-2 (COX-2)] is an enzyme induced by proinflammatory stimuli that is often overexpressed in malignant tissue and involved in the synthesis of prostaglandins and thromboxanes, regulators of processes such as inflammation, cell proliferation, and angiogenesis, all relevant for cancer development. We investigated whether a functional genetic polymorphism, rs5277, in COX-2 may have a risk-modifying effect on sporadic colorectal cancer in an Iranian population. Materials and Methods: We conducted a case-control study on 167 patients with colorectal cancer and 197 cancer-free controls in Taleghani Hospital in Tehran, Iran, between 2007 and 2011. Peripheral blood samples of both groups were processed for DNA extraction and genotyping of the COX-2 gene polymorphism (rs5277) using PCR-RFLP. RFLP results were confirmed by direct sequencing. Logistic regression analysis was performed to calculate the adjusted odds ratio (OR) and 95% confidence interval (95% CI). Results: There was no significant difference in the distribution of COX-2 gene rs5277 polymorphism genotype and the allelic form, among CRC patients compared with the healthy control group (p: 0.867). Conclusions: Our results suggest that rs5277 polymorphism in COX2 could not be a good prognostic indicator for patients with CRC.
    Asian Pacific journal of cancer prevention: APJCP 04/2014; 15(8):3507-11. DOI:10.7314/APJCP.2014.15.8.3507 · 1.50 Impact Factor

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Jun 1, 2014

Kim N Danforth