An association between the PTGS2 rs5275 polymorphism and colorectal cancer risk in families with inherited non-syndromic predisposition

Ross, Jason; Lockett, Linda; Brookes, Diana; Tabor, Bruce; Duesing, Konsta; Buckley, Michael; Lockett, Trevor; Molloy, Peter; Macrae, Finlay; Young, Graeme; Blanco, Ignacio; Capella, Gabriel; Hannan, Garry N
December 2013
European Journal of Human Genetics;Dec2013, Vol. 21 Issue 12, p1389
Academic Journal
Recently our group completed a genome-wide linkage study investigating Australian and Spanish families with inherited risk of colorectal cancer (CRC). A minor linkage peak from that study located on chromosome 1 correlates with the location of a known CRC risk-modifying gene, prostaglandin synthase (PTGS2). PTGS2 encodes the inducible prostaglandin synthase enzyme cyclooxygenase-2 (COX-2). Prostaglandins are implicated in the initiation of carcinogenesis and progression of tumours. Sequencing of PTGS2 in a small subset of affected individuals identified a high frequency of the minor C allele of single nucleotide polymorphism rs5275. We then genotyped the rs5275 polymorphism in 183 affected and 223 unaffected individuals from our CRC predisposed families. Tests for association in the presence of linkage were made using family-based association tests. The C allele was found to be significantly associated (P<0.01) with diagnosis of hereditary non-syndromic CRC (P=0.0094, dominant model) and an earlier age of diagnosis (P=0.0089, heterozygous-advantage model). Interestingly, by stratifying the age of diagnosis data, we observed a speculative gender-discordant effect. Relative to other groups, female CC carriers were diagnosed less when young, but by 60 years of age were the most at risk group. Conversely, CT carriers of both genders showed a consistently earlier diagnosis relative to TT carriers. Our results suggest potential differential age-and gender-dependent efficacies of chemopreventative COX-2 inhibitors in the context of non-syndromic colorectal cancer.


Related Articles

  • The collagenase-1 (MMP-1) gene promoter polymorphism - 1607/2G is associated with favourable prognosis in patients with colorectal cancer. Hettiaratchi, A.; Hawkins, N. J.; McKenzie, G.; Ward, R. L.; Hunt, J. E.; Wakefield, D.; Di Girolamo, N. // British Journal of Cancer;3/12/2007, Vol. 96 Issue 5, p783 

    Matrix metalloproteinase (MMP) overexpression has been implicated in the pathogenesis of colorectal carcinoma (CRC). Accumulating evidence suggests that MMP promoter single nucleotide polymorphisms (SNPs) effecting gene transcription are associated with enhanced susceptibility for the...

  • The C/A polymorphism in intron 11 of the XPC gene plays a crucial role in the modulation of an individual's susceptibility to sporadic colorectal cancer. Gil, Justyna; Ramsey, Dave; Stembalska, Agnieszka; Karpinski, Pawel; Pesz, Karolina; Laczmanska, Izabela; Leszczynski, Przemyslaw; Grzebieniak, Zygmunt; Sasiadek, Maria // Molecular Biology Reports;Jan2012, Vol. 39 Issue 1, p527 

    Epidemiological data show that colorectal cancer (CRC) is the second most frequent malignancy worldwide. The involvement of 'minor impact genes' such as XME and DNA-repair genes in the etiology of sporadic cancer has been postulated by other authors. We focused on analyzing polymorphisms in...

  • Granzyme B gene polymorphisms, colorectal cancer risk, and metastasis. Mhaidat, Nizar M.; Al-azzam, Sayer I.; Alzoubi, Karem H.; Khabour, Omar F.; Gharaibeh, Baraa F. // Journal of Cancer Research & Therapeutics;Jul-Sep2014, Vol. 10 Issue 3, p587 

    Context: The human granzyme B protein (GrB), which is encoded by granzyme B gene (GZMB), plays a major role in eliminating cancer cells. Polymorphisms of GZMB gene such as Q55R, P94A, and Y247H have been shown to affect GrB activity and the subsequent cancer risk. Aims: In this study, we...

  • P-0174 ASSOCIATION BETWEEN COLORECTAL CANCER SURVIVAL OUTCOMES AND GWAS-IDENTIFIED COLORECTAL CANCER SUSCEPTIBILITY POLYMORPHISM IN KOREAN POPULATION. Woog, Kang Byung; Gwang, Kim Jong; Soo, Chae Yee; Kyu, Jung Min; Yun-Jin, Jang; Ohkyoung, Kwon; Hyo-sung, Jeon // Annals of Oncology;Jun2014, Vol. 25 Issue suppl_2, pii67 

    No abstract available.

  • Susceptibility and REF1 Gene Polymorphism Towards Colorectal Cancer. Yang, Shibin; Lai, Yuanhui; Xiao, Longbin; Han, Fanghai; Wu, Wenhui; Long, Shuo; Li, Wenfeng; He, Yulong // Cell Biochemistry & Biophysics;Mar2015, Vol. 71 Issue 2, p977 

    Published data on the relation between REF1 polymorphism and colorectal cancer risk showed inconclusive results. The aim of this study was to derive a comprehensive estimation of the association. Data on association between REF1 polymorphism and colorectal cancer risk were summarized. The...

  • Polymorphisms within inflammatory genes and colorectal cancer. Landi, Stefano; Gemignani, Federica; Bottari, Fabio; Gioia-Patricola, Lydie; Guino, Elisabet; Cambray, MarĂ­a; Biondo, Sebastiano; Capella, Gabriel; Boldrini, Laura; Canzian, Federico; Moreno, Victor // Journal of Negative Results in Biomedicine;2006, Vol. 5, p15 

    Background: Chronic inflammation is a risk factor for colorectal cancer and polymorphisms in the inflammatory genes could modulate the levels of inflammation. We have investigated ten single nucleotide polymorphisms (SNPs) in the following inflammation-related genes: TLR4 (Asp299Gly), CD14 (-260...

  • MTHFR 677 C>T and 1298 A>C polymorphisms and the age of onset of colorectal cancer in hereditary nonpolyposis colorectal cancer. Reeves, Stuart G.; Meldrum, Cliff; Groombridge, Claire; Spigelman, Allan D.; Suchy, Janina; Kurzawski, Grzegorz; Lubinski, Jan; McElduff, Patrick; Scott, Rodney J. // European Journal of Human Genetics;May2009, Vol. 17 Issue 5, p629 

    Hereditary non-polyposis colorectal cancer (HNPCC) or Lynch syndrome is characterized by inactivating germline mutations in DNA mismatch repair genes resulting in an increased risk of developing an epithelial malignancy. There is considerable variability in disease expression observed in this...

  • DNA Repair Gene 8-Oxoguanine DNA Glycosylase Ser326Cys Polymorphism and Colorectal Cancer Risk in a Kashmiri Population. Sameer, A. Syed; Nissar, Saniya; Abdullah, Safiya; Chowdri, Nissar A.; Siddiqi, Mushtaq A. // DNA & Cell Biology;Apr2012, Vol. 31 Issue 4, p541 

    8-Oxoguanine DNA glycosylase (OGG1) is one of the important base excision repair enzymes that repair 8-oxoguanine lesion incorporated within the DNA of an individual by reactive oxygen species. The aim of this study was to detect the role of OGG1 Ser326Cys polymorphism in susceptibility to...

  • Intron 3 16 bp duplication polymorphism of TP53 contributes to cancer susceptibility: a meta-analysis. Zheng Hu; Xiang Li; Xincai Qu; Yungang He; Ring, Brian Z.; Song, Enmin; Li Su // Carcinogenesis;Apr2010, Vol. 31 Issue 4, p643 

    A few genetic polymorphisms of TP53 are known to have a significant effect on cancer susceptibility. Intron 3 16 bp duplication polymorphism of TP53 has been reported to be associated with breast cancer, colorectal cancer, lung cancer and other cancers, but the reported results remain...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics