PURPOSE: We identified recently the extracellular matrix (ECM) receptor interaction pathway as a consistently overrepresented category among gene expression profiling studies on colorectal cancer (CRC) prognosis. METHODS: Putative regulatory single nucleotide polymorphisms (SNPs) in genes from the ECM pathway were genotyped in 613 CRC patients from Northern Germany (PopGen cohort) and tested for association with disease progression and survival. RESULTS: The eSNP (SNP associated with expression) rs12695175 in CD47 associated with CRC specific survival (HR = 2.18, 95 % CI 1.10-4.33, CC versus AA) and with overall survival (HR = 1.99, 95 % CI 1.04-3.81, CC versus AA). This association remained significant after adjustment for age at diagnosis, tumour stage (T) and lymph node status (N). Three polymorphisms in CD47 were associated with distant metastasis in a dominant model: rs9879947 and rs3206652 in the 3'-UTR (OR = 1.64, 95 % CI 1.01-2.64 and OR = 1.88, 95 % CI 1.27-2.80, respectively) and the eSNP rs3804639 (OR = 1.73, 95 % CI 1.17-2.57). CONCLUSIONS: The novel associations of eSNPs in CD47 with worse survival and distant metastasis should be confirmed by additional studies, since increased expression of this gene has recently been shown to be an indicator of poor prognosis in cancer patients.
PURPOSE: We identified recently the extracellular matrix (ECM) receptor interaction pathway as a consistently overrepresented category among gene expression profiling studies on colorectal cancer (CRC) prognosis. METHODS: Putative regulatory single nucleotide polymorphisms (SNPs) in genes from the ECM pathway were genotyped in 613 CRC patients from Northern Germany (PopGen cohort) and tested for association with disease progression and survival. RESULTS: The eSNP (SNP associated with expression) rs12695175 in CD47 associated with CRC specific survival (HR = 2.18, 95 % CI 1.10-4.33, CC versus AA) and with overall survival (HR = 1.99, 95 % CI 1.04-3.81, CC versus AA). This association remained significant after adjustment for age at diagnosis, tumour stage (T) and lymph node status (N). Three polymorphisms in CD47 were associated with distant metastasis in a dominant model: rs9879947 and rs3206652 in the 3'-UTR (OR = 1.64, 95 % CI 1.01-2.64 and OR = 1.88, 95 % CI 1.27-2.80, respectively) and the eSNP rs3804639 (OR = 1.73, 95 % CI 1.17-2.57). CONCLUSIONS: The novel associations of eSNPs in CD47 with worse survival and distant metastasis should be confirmed by additional studies, since increased expression of this gene has recently been shown to be an indicator of poor prognosis in cancerpatients.
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Authors: Laura D Wood; D Williams Parsons; Siân Jones; Jimmy Lin; Tobias Sjöblom; Rebecca J Leary; Dong Shen; Simina M Boca; Thomas Barber; Janine Ptak; Natalie Silliman; Steve Szabo; Zoltan Dezso; Vadim Ustyanksky; Tatiana Nikolskaya; Yuri Nikolsky; Rachel Karchin; Paul A Wilson; Joshua S Kaminker; Zemin Zhang; Randal Croshaw; Joseph Willis; Dawn Dawson; Michail Shipitsin; James K V Willson; Saraswati Sukumar; Kornelia Polyak; Ben Ho Park; Charit L Pethiyagoda; P V Krishna Pant; Dennis G Ballinger; Andrew B Sparks; James Hartigan; Douglas R Smith; Erick Suh; Nickolas Papadopoulos; Phillip Buckhaults; Sanford D Markowitz; Giovanni Parmigiani; Kenneth W Kinzler; Victor E Velculescu; Bert Vogelstein Journal: Science Date: 2007-10-11 Impact factor: 47.728