Effect of COX2 -765G&gt;C and c.3618A&gt;G polymorphisms on the risk and survival of sporadic colorectal cancer

Iglesias, Daniel; Nejda, Nargisse; Azcoita, M Moreno; González-Aguilera, Juan J.; Fernández-Peralta, Antonia M.

doi:10.1007/s10552-009-9368-1

Cited by 30 publications

(29 citation statements)

References 42 publications

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“…Iglesias et al (35) have recently reported that the c.3618A/G (rs4648298) polymorphism located in the 3′ flanking regions of COX-2 was associated with improved survival of colorectal cancer patients in Caucasians. However, in our previous study, it was shown that c.3618A/G (rs4648298) variant was not a common polymorphism in Han Chinese population (major allele frequency, <0.05; ref.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, a personalized more intensive treatment, i.e., a combination treatment of chemoradiotherapy and COX-2 inhibitor, might be warranted to improve the survival in patients with the unfavorable COX-2 −1195AA genotype. Several phase II studies failed to show the value of eicosanoid inhibition in addition to other modalities, such as chemotherapy, and/or tyrosine kinase inhibitor target therapy, in unselected population of advanced NSCLC (35,38,(41)(42)(43). However, recent evidence suggested a potential advantage for celecoxib, a selective COX-2 inhibitor, might be obtained in the certain population (44,45).…”

Section: Discussionmentioning

confidence: 99%

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Cyclooxygenase-2 Genetic Variants Are Associated with Survival in Unresectable Locally Advanced Non–Small Cell Lung Cancer

Yang

Zhang

et al. 2010

Clinical Cancer Research

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Purpose: Cyclooxygenase-2 (COX-2) plays important roles in the modulation of apoptosis, angiogenesis, immune response, and tumor invasion. Elevated COX-2 expression has been reported to be correlated with reduced survival after radiotherapy. This study examined whether genetic variations in the COX-2 gene are associated with different survival in inoperable locally advanced non-small cell lung cancer (NSCLC) treated with chemoradiotherapy or radiotherapy alone.Experimental Design: One hundred and thirty-six patients with inoperable stage IIIA-B NSCLC receiving thoracic irradiation between 2004 and 2007 were recruited in this study. Five functional COX-2 polymorphisms were genotyped using DNA from blood lymphocytes. Kaplan-Meier methods were used to compare survival by different genotypes. Cox proportional hazards models were used to identify independently significant variables.Results: During the median 22.4 months of follow-up, the favorable COX-2 −1195GA and GG genotypes were significantly correlated with better overall survival (20.2 months versus 15.7 months; P = 0.006; hazard ratio (HR), 0.58; 95% confidence interval (CI), 0.39-0.86) and with longer progressfree survival (11.9 months versus 9.5 months; P = 0.034) compared with the −1195AA genotype. No significant associations were found among other COX-2 polymorphisms and clinical outcomes. In the multivariate Cox proportional hazards model, COX-2 −1195G/A polymorphism was independently associated with overall survival after adjusting the clinicopathologic factors (P = 0.008; HR, 0.58; 95% CI, 0.39-0.87).Conclusion: COX-2 −1195G/A polymorphism is a potential predictive marker of survival in locally advanced NSCLC patients treated with chemoradiotherapy or radiotherapy alone. Clin Cancer Res; 16(8); 2383-90. ©2010 AACR.Non-small cell lung cancer (NSCLC) accounts for >80% of primary lung cancers and about one third of NSCLC patients are diagnosed at a locally advanced stage (1). Treatment of these patients is usually based on a multidisciplinary strategy, including a combination of radiotherapy and chemotherapy. However, results of these treatments were unsatisfactory with a 3-year overall survival (OS) being 10% to 20% (2). The classic prognostic determinants for lung cancer include the tumornode-metastasis staging system, performance status, sex, and weight loss. Unfortunately, all these factors are far less than sufficient to explain the patient-to-patient variability. Therefore, identification of new biomarkers for more accurate prognostic and predictive assessment is warranted and could be helpful to highlight the possibility of patient-tailored decisions (3).Cyclooxygenase (COX, also known as prostaglandin endoperoxide synthase) is a key enzyme that catalyzes the conversion of arachidonic acid into prostaglandins (4).

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Cyclooxygenase-2 Genetic Variants Are Associated with Survival in Unresectable Locally Advanced Non–Small Cell Lung Cancer

Yang

Zhang

et al. 2010

Clinical Cancer Research

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“…Thus, a final total of 38 case-control studies in 37 articles which met our inclusion criteria were identified, including 10814 cases and 16174 controls. Among 38 cases and controls, there were 20 case-controls of Asians (Hamajima et al, 2001;Koh et al, 2004;Liu et al, 2006;Guo et al, 2007;Tan et al, 2007;Chiang et al, 2008;Lin et al, 2008;Saxena et al, 2008;Ueda et al, 2008;Xing et al, 2008;Xu et al, 2008;Tang et al, 2009;Upadhyay et al, 2009;Zhao et al, 2009;Mittal et al, 2010;He et al, 2011;Chang et al, 2012;Li et al, 2012;Shin et al, 2012), 11 of Caucasians (Cox et al, 2004;Pereira et al, 2006;Hou et al, 2007;Moons et al, 2007;Sitarz et al, 2008;Andersen et al, 2009;Hoff et al, 2009;Iglesias et al, 2009;Kristinsson et al, 2009;Pereira et al, 2010;Daraei et al, 2012), 4 of Americans (Ulrich et al, 2005;Gunter et al, 2006;Gong et al, 2009;Thompson et al, 2009), and 1 of Africans (Bye et al, 2011), and 2 of Mixed (Bye et al, 2011;Wang et al, 2012). 9 investigated gastric cancer (Liu ...…”

Section: Study Inclusion and Characteristicsmentioning

confidence: 99%

“…9 investigated gastric cancer (Liu et al, 2006;Pereira et al, 2006;Hou et al, 2007;Saxena et al, 2008;Sitarz et al, 2008;Tang et al, 2009;Li et al, 2012;Shin et al, 2012), 16 investigated colorectal cancer (Hamajima et al, 2001;Cox et al, 2004;Koh et al, 2004;Ulrich et al, 2005;Gunter et al, 2006;Xing et al, 2008;Ueda et al, 2008;Andersen et al, 2009;Gong et al, 2009;Hoff et al, 2009;Iglesias et al, 2009;Thompson et al, 2009;Pereira et al, 2010;Daraei et al, 2012;Wang et al, 2012), 3 investigated oral cancer (Chiang et al, 2008;Lin et al, 2008;Mittal et al, 2010), 6 investigated esophageal cancer (Guo et al, 2007;Moons et al, 2007;Kristinsson et al, 2009;Upadhyay et al, 2009;Bye et al, 2011), and 4 investigated pancreatic cancer and hepatocellular carcinoma (HCC) (Xu et al, 2008;Zhao et al, 2009;He et al, 2011;Chang et al, 2012). Of these articles, 18 studies were performed in HB (Hamajima et al, 2001;Cox et al, 2004;Gunter et al, 2006;Pereira et al, 2006;…”

Section: Study Inclusion and Characteristicsmentioning

confidence: 99%

The -765G>C Polymorphism in the Cyclooxygenase-2 Gene and Digestive System Cancer: a Meta-analysis

Zhao

Cao²,

Zhu³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Background: Published data regarding associations between the -765G>C polymorphism in cyclooxygenase-2 (COX-2) gene and digestive system cancer risk have been inconclusive. The aim of this study was to comprehensively evaluate the genetic risk of the -765G>C polymorphism in the COX-2 gene for digestive system cancer. Materials and Methods: A search was performed in Pubmed, Medline (Ovid), Embase, CNKI, Weipu, Wanfang and CBM databases, covering all studies until Feb 10, 2014. Statistical analysis was performed using Revman5.2. Results: A total of 10,814 cases and 16,174 controls in 38 case-control studies were included in this meta-analysis. The results indicated that C allele carriers (GC+CC) had a 20% increased risk of digestive system cancer when compared with the homozygote GG (odds ratio (OR)=1.20, 95% confidence interval (CI), 1.00-1.44 for GC+CC vs GG). In the subgroup analysis by ethnicity, significant elevated risks were associated with C allele carriers (GC+CC) in Asians (OR = 1.46, 95% CI=1.07-2.01, and p=0.02) and Africans (OR=2.12, 95% CI=1.57-2.87, and p< 0.00001), but not among Caucasians, Americans and mixed groups. For subgroup analysis by cancer type (GC+CC vs GG), significant associations were found between the -765G>C polymorphism and higher risk for gastric cancer (OR=1.64, 95% CI=1.03-2.61, and p=0.04), but not for colorectal cancer, oral cancer, esophageal cancer, and others. Regarding study design (GC+CC vs GG), no significant associations were found in then population-based case-control (PCC), hospital-based case-control (HCC) and family-based case-control (FCC) studies. Conclusions: This meta-analysis suggested that the -765G>C polymorphism of the COX-2 gene is a potential risk factor for digestive system cancer in Asians and Africans and gastric cancer overall.

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“…1). Finally, 10 valid case-control studies (Hamajima et al 2001;Cox et al 2004;Koh et al 2004;Tan et al 2007;Xing et al 2008;Andersen et al 2009;Hoff et al 2009;Iglesias et al 2009;Thompson et al 2009;Pereira et al 2010) of the association between COX2 promoter -765G/C polymorphisms and CRC risk, totaling 3,322 cancer cases and 5,166 controls, were used for this meta-analysis. Of these studies, four were conducted on Caucasian descendants, and six on Asian descendants.…”

Section: Study Characteristicsmentioning

confidence: 99%

The -765C Allele of the Cyclooxygenase-2 Gene as a Potential Risk Factor of Colorectal Cancer: A Meta-Analysis

Cao

Long

et al. 2010

Tohoku J. Exp. Med.

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Colorectal cancer (CRC) is the third leading cause of cancer-related death in the world. Human colorectal carcinogenesis is a complex, multistep and multigenetic process. Cyclooxygenase-2 (COX2), a key enzyme in arachidonic acid metabolism, is overexpressed in several epithelial malignancies including colorectal cancer. COX2 expression can be induced by pro-inflammatory and mitogenic stimuli. The -765G/C polymorphism of the COX2 gene promoter has been reported to affect CRC susceptibility, but recent studies have demonstrated conflicting results. To shed light on these inconclusive findings, we performed a meta-analysis for assessing the involvement of COX2 -765G/C polymorphisms at the onset of colorectal carcinoma. Literature-based searching was guided to gather data and either fixed-effect or random-effect model was used to pool the odds ratio (OR) according to the test of heterogeneity. The 10 eligible case-control studies included 3,322 colorectal cancer cases and 5,166 controls. Overall, no evidence has indicated that individuals carrying GC+CC genotypes had significantly increased colorectal cancer risk compared with GG genotype [OR = 1.06, 95% confidence interval (95% CI) = 0.94-1.20]. However, stratified analysis with ethnicity indicated that individuals carrying GC+CC genotypes had an increased risk of colorectal cancer (OR = 1.40, 95% CI = 1.11-1.76) among Asian population. In conclusion, although not all bias could be eliminated, the -765C allele of the COX2 gene may be a potential risk factor for colorectal cancer in Asians.

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Effect of COX2 -765G>C and c.3618A>G polymorphisms on the risk and survival of sporadic colorectal cancer

Abstract: The current results suggested that c.3618A>G polymorphism in COX2 is a good prognostic indicator for patients with CRC. Genotyping this polymorphism may be useful for predicting the clinical outcome of sporadic CRC.

Cited by 30 publications

References 42 publications

Cyclooxygenase-2 Genetic Variants Are Associated with Survival in Unresectable Locally Advanced Non–Small Cell Lung Cancer

Cyclooxygenase-2 Genetic Variants Are Associated with Survival in Unresectable Locally Advanced Non–Small Cell Lung Cancer

The -765G>C Polymorphism in the Cyclooxygenase-2 Gene and Digestive System Cancer: a Meta-analysis

The -765C Allele of the Cyclooxygenase-2 Gene as a Potential Risk Factor of Colorectal Cancer: A Meta-Analysis

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