The cyclooxygenase-2 (PTGS2) 8473T&amp;gt;C polymorphism is associated with breast cancer risk.

Langsenlehner, Uwe; Yazdani‐Biuki, Babak; Eder, Tanja; Renner, Wilfried; Wascher, Thomas C.; Paulweber, Bernhard; Weitzer, Werner; Samonigg, Hellmut; Krippl, Peter

doi:10.1158/1078-0432.ccr-05-2055

Cited by 74 publications

(77 citation statements)

References 19 publications

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“…Several studies have investigated the association between the COX-2 8473T¨C polymorphism and the risk of several types of cancer (8)(9)(10)(11)(12)25). Our data are in accordance with three previous studies, which showed a similar association with the CC genotype in lung (10), colorectal (12) and breast Table I.…”

Section: Discussionsupporting

confidence: 91%

“…patients controls Genotypes (%) (%) OR (95% CI) P- value ----------------------------------------------- -------------------------------------------------GC, gastric cancer; CI, confident interval. (11). Three other studies described a protective role for the CC genotype in lung cancer (8,9,25).…”

Section: -------------------------------------------------mentioning

confidence: 99%

“…It has been suggested that the COX-2 8473T¨C 3'-untranslated region (UTR) variant affects COX-2 mRNA levels (7), because this polymorphism is located in the post transcriptional regulatory region. The COX-2 polymorphism at the 8473 position has recently been associated with lung, breast and colorectal cancer (8)(9)(10)(11)(12). However, the association of this variant with gastric cancer risk has not been studied previously.…”

Section: Introductionmentioning

confidence: 99%

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A polymorphism in the 3'-utr of cyclooxygenase-2 and the risk of gastric cancer

Shibata

Arisawa

Tahara³

et al. 2008

Mol Med Report

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Abstract.A polymorphism within the 3'-UTR 8473T¨C of the cyclooxygenase-2 (COX-2) gene, which plays a role in gastrointestinal cancer development, has been associated with susceptibility to malignant disease. Here, we report on the interaction between the COX-2 3'-UTR T¨C polymorphism and gastric cancer development. DNA from 121 Japanese patients with gastric cancer and 126 age-matched control patients was examined for the COX-2 polymorphism by PCR-RFLP. Odds ratios and the 95% confidence interval (CI) were calculated. Homozygous carriage of the COX-2 8473C allele tended to be associated with an increased risk of gastric cancer compared to the T allele homozygotes of the subjects (OR=3.70; 95% CI, 0.96-14.25). The CC allele was associated with a significant increased risk of diffuse-type gastric cancer (OR=5.29; 95% CI, 1.18-23.70). These findings suggest that the COX-2 3'-UTR 8473T¨C polymorphism could be used as a marker for genetic susceptibility to gastric cancer in Japanese populations.

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Section: Discussionsupporting

confidence: 91%

Section: -------------------------------------------------mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A polymorphism in the 3'-utr of cyclooxygenase-2 and the risk of gastric cancer

Shibata

Arisawa

Tahara³

et al. 2008

Mol Med Report

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“…In accordance, the exon10+837T>C SNP was also related to a reduction in lung cancer risk in Korean and Chinese populations (42,43). However, it has also been reported to increase the susceptibility to breast cancer in Austrians (44). Despite study design differences and population stratifications, the pivotal and complicated role of PTGS2 in tumorigenesis might partially explain the apparent discrepancies in these findings.…”

Section: Discussionmentioning

confidence: 75%

Profiling of Genetic Variations in Inflammation Pathway Genes in Relation to Bladder Cancer Predisposition

Yang¹,

Gu²,

Lin³

et al. 2008

Clinical Cancer Research

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Purpose: Compelling evidence has indicated that inflammation plays an important role in cancer development.We sought to test the hypothesis that common sequence variants in the inflammation pathway modulate bladder cancer risk. Experimental Design: We genotyped 59 potentially functional single nucleotide polymorphisms from 35 candidate inflammation genes in a case-control study including 635 Caucasian bladder cancer patients and 635 matched controls. Results: The most significant finding was in the 3 ¶-untranslated region of PTGS2 (exon10+ 837T>C, rs5275), which was associated with a significantly reduced risk (odds ratio, 0.68; 95% confidence interval, 0.54-0.87; P = 0.002) and remained significant after multiple comparison adjustment. Consistently, the most common PTGS2 haplotype containing the common allele of exon10+837T>C was associated with a significantly increased risk (odds ratio, 1.27; 95% confidence interval, 1.06-1.52; P = 0.008). In contrast, the haplotypes containing at least one variant allele of exon10+837T>C were all associated with a decreased risk. In a combined analysis to assess the cumulative effects of inflammation single nucleotide polymorphisms on bladder cancer risk, we found that in the anti-inflammation pathway, but not in the proinflammation pathway, when compared with individuals with a few adverse alleles, individuals with more adverse alleles had a significantly increased risk in a dose-dependent manner (P trend = 0.012). To further elucidate the functional mechanism of these associations, we redefined the adverse alleles based on literature-reported functional results and found that individuals with a higher number of inflammation-enhancing alleles in the anti-inflammation pathway exhibited a greater bladder cancer risk. Conclusions: Our results strongly suggest that common variants in inflammation genes affect bladder cancer susceptibility individually and jointly.

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“…Langsenlehner et al (28) showed a positive association between PTGS2(04)rs5275 SNP and breast cancer risk (rare homozygote, CC; P = 0.002; OR, 2.05; 95% CI, 1.30-3.25), whereas Cox et al (29) excluded an increase in breast cancer susceptibility but raised the possibility of an inverse association between this polymorphism and breast cancer risk (rare homozygote, CC; P = 0.05; OR, 0.80; 95% CI, 0.62-1.03). In our study, this SNP was not significantly associated with breast cancer susceptibility (P heterogeneity = 0.66 and P trend = 0.36; OR, 1.0; 95% CI, 0.8-1.3) or survival (hazard ratio, 1.05; 95% CI, 0.9-1.23; P trend = 0.52).…”

Section: Discussionmentioning

confidence: 99%

Common Polymorphisms in the Prostaglandin Pathway Genes and Their Association with Breast Cancer Susceptibility and Survival

Abraham

Harrington

Driver

et al. 2009

Clinical Cancer Research

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Purpose: There is evidence that genetic variation in the prostaglandin pathway affects cancer susceptibility and progression. Conflicting data from several studies exist for the association of PTGS2 (cyclooxygenase 2) polymorphisms with breast cancer risk.We investigated associations between common germ-line variations in seven genes in the prostaglandin pathway and breast cancer susceptibility and survival among women with invasive breast cancer in the SEARCH study. Experimental Design: DNA samples from 9,030 cases and controls were genotyped for 64 single nucleotide polymorphisms tagging known common variants (minor allele frequency > 0.05) in PTGS1, PTGS2,TBXAS1, PTGIS, PTGES, PTGDS, and PGDS with a two-stage case-control study design. Results: Four tagging single nucleotide polymorphisms showed modest association with breast cancer susceptibility. All four fit a recessive genetic model. Minor allele homozygotes for PTGISrs5602 [odds ratio (OR), 1.15; 95% confidence interval (95% CI), 1.04-1.27; P = 0.005], PTGISrs8183919 (OR, 1.22; 95% CI, 1.06-1.41; P = 0.006), and TBXASrs41727 (OR, 1.83; 95% CI, 1.22-2.73; P = 0.003) are associated with an increased risk compared with common allele carriers. For PTGISrs44627 minor allele homozygotes (OR, 0.66; 95% CI, 0.5-0.86; P = 0.002), a protective effect was observed. Conclusion: Specific PTGIS and TBXAS1 variants may affect breast cancer susceptibility, but common variants in PTGS1, PTGS2, PTGES, PTGDS, and PGDS have no major role in breast cancer susceptibility. None of the variants in the seven genes studied appear to affect survival. Further larger studies correlating clinical and genotypic data are required to establish if the clinical utility of prostaglandin-targeted therapies, as chemoprevention agents, is influenced by an individual's profile of genetic variants in key prostaglandin pathway genes.Breast cancer is the most common cancer among women in developed countries and accounts for 18% of all cancers (1). Although a few, rare, strongly predisposing alleles are well established (e.g., deleterious alleles of BRCA1 and BRCA2), these account for only 2% to 5% of all breast cancer cases (2) and <25% of the excess familial risk of breast cancer can be explained by variants in the known susceptibility genes (3). It is likely that the unexplained excess is due to multiple low to moderate risk alleles in numerous genes, that is, a polygenic model of cancer susceptibility (4).There has been increasing interest in the role of the prostaglandin pathway in both cancer susceptibility and tumor progression, with a particular focus on the enzyme cyclooxygenase (COX)

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The cyclooxygenase-2 (PTGS2) 8473T>C polymorphism is associated with breast cancer risk.

Cited by 74 publications

References 19 publications

A polymorphism in the 3'-utr of cyclooxygenase-2 and the risk of gastric cancer

A polymorphism in the 3'-utr of cyclooxygenase-2 and the risk of gastric cancer

Profiling of Genetic Variations in Inflammation Pathway Genes in Relation to Bladder Cancer Predisposition

Common Polymorphisms in the Prostaglandin Pathway Genes and Their Association with Breast Cancer Susceptibility and Survival

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