BACKGROUND: The COX2 gene (also known as PTGS2) encodes one of the essential cyclooxygenases for the prostanoid synthesis, and its expression is tightly regulated at both transcriptional and posttranscriptional levels. COX2 overexpression has been detected in up to 90% of colon carcinomas, and its downregulation inhibits polyp formation. Several polymorphisms located in both 5'- and 3'- flanking regions of COX2 have been described, but their functional significance and their use as prognostic indicators are still unclear. METHOD: We analyzed in Spanish population the risk contribution and the prognostic significance for colorectal cancer (CRC) with five polymorphisms (rs20417, rs20426, rs5276, rs13306035 and rs4648298) located in the coding and regulatory regions of COX2. RESULTS: Only two variants appear in Spanish population: -765G>C (rs20417) located at the promoter and c.3618A>G (rs4648298) in the 3'UTR. None of the two polymorphisms associate with colon cancer risk (HR of 1.42; 95% CI = 0.46-4.47 and 0.62; 95% CI: 0.305-1.267, respectively). Moreover, the multifactor dimensionality reduction method does not detect high- or low-risk genotype combinations (training accuracy: 0.52; testing accuracy: 0.45; cross-validation consistency (CVC): 10/10; p = 0.37), indicating that there are no synergist interactions between these polymorphisms that alter the risk of cancer. However, the variant of the c.3618A>G polymorphism is associated with the presence of several clinicopathological features that have been shown to be good prognostic indicators. In addition, patients with the c.3618A>G polymorphism also show improved survival rates (log rank, p = 0.026). CONCLUSION: 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.
BACKGROUND: The COX2 gene (also known as PTGS2) encodes one of the essential cyclooxygenases for the prostanoid synthesis, and its expression is tightly regulated at both transcriptional and posttranscriptional levels. COX2 overexpression has been detected in up to 90% of colon carcinomas, and its downregulation inhibits polyp formation. Several polymorphisms located in both 5'- and 3'- flanking regions of COX2 have been described, but their functional significance and their use as prognostic indicators are still unclear. METHOD: We analyzed in Spanish population the risk contribution and the prognostic significance for colorectal cancer (CRC) with five polymorphisms (rs20417, rs20426, rs5276, rs13306035 and rs4648298) located in the coding and regulatory regions of COX2. RESULTS: Only two variants appear in Spanish population: -765G>C (rs20417) located at the promoter and c.3618A>G (rs4648298) in the 3'UTR. None of the two polymorphisms associate with colon cancer risk (HR of 1.42; 95% CI = 0.46-4.47 and 0.62; 95% CI: 0.305-1.267, respectively). Moreover, the multifactor dimensionality reduction method does not detect high- or low-risk genotype combinations (training accuracy: 0.52; testing accuracy: 0.45; cross-validation consistency (CVC): 10/10; p = 0.37), indicating that there are no synergist interactions between these polymorphisms that alter the risk of cancer. However, the variant of the c.3618A>G polymorphism is associated with the presence of several clinicopathological features that have been shown to be good prognostic indicators. In addition, patients with the c.3618A>G polymorphism also show improved survival rates (log rank, p = 0.026). CONCLUSION: 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.
Authors: Karen W Makar; Elizabeth M Poole; Alexa J Resler; Brenna Seufert; Karen Curtin; Sarah E Kleinstein; David Duggan; Richard J Kulmacz; Li Hsu; John Whitton; Christopher S Carlson; Christine F Rimorin; Bette J Caan; John A Baron; John D Potter; Martha L Slattery; Cornelia M Ulrich Journal: Cancer Causes Control Date: 2013-12 Impact factor: 2.506
Authors: Anna E Coghill; Polly A Newcomb; Elizabeth M Poole; Carolyn M Hutter; Karen W Makar; Dave Duggan; John D Potter; Cornelia M Ulrich Journal: Clin Cancer Res Date: 2011-10-05 Impact factor: 12.531
Authors: Amanda I Phipps; Polly A Newcomb; Xabier Garcia-Albeniz; Carolyn M Hutter; Emily White; Charles S Fuchs; Aditi Hazra; Shuji Ogino; Hongmei Nan; Jing Ma; Peter T Campbell; Jane C Figueiredo; Ulrike Peters; Andrew T Chan Journal: Gastroenterology Date: 2012-05-08 Impact factor: 22.682
Authors: María Asunción García-González; David Nicolás-Pérez; Angel Lanas; Luis Bujanda; Patricia Carrera; Rafael Benito; Mark Strunk; Federico Sopeña; Santos Santolaria; Elena Piazuelo; Pilar Jiménez; Rafael Campo; Jesús Espinel; Marisa Manzano; Fernando Geijo; María Pellisé; Ferrán González-Huix; Jorge Espinós; Manuel Zaballa; Llúcia Titó; Luis Barranco; Roberto Pazo; Enrique Quintero Journal: PLoS One Date: 2012-09-28 Impact factor: 3.240