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Polymorphisms in the transforming growth factor beta 1 pathway in relation to colorectal cancer progression
Department of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany / Center for Primary Health Care Research, Clinical Research Center, Lund University, Malmö, Sweden. (Center for Primary Health Care Research, Clinical Research Center, Lund University, Malmö, Sweden)
Department of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany.
Department of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany.
Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
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2010 (English)In: Genes, Chromosomes and Cancer, ISSN 1045-2257, E-ISSN 1098-2264, Vol. 49, no 3, 270-281 p.Article in journal (Refereed) Published
Abstract [en]

Transforming growth factor beta1 (TGFB1) acts as a growth inhibitor of normal colonic epithelial cells, however, as a tumor promoter of colorectal cancer (CRC) cells. To explore the association between genetic polymorphisms in the TGFB1 pathway and CRC susceptibility and clinical outcome, we carried out a case-control study on a Swedish population of 308 CRC cases and 585 age- and gender-matched controls. The cases were sampled prospectively and had up to 16 years follow-up, making the study material particularly suitable for survival analysis. On the basis of their reported or predicted functional effect, nine single-nucleotide polymorphisms (TGFB1: Leu10Pro; TGFBR1: 9A/6A and IVS7G+24A; FURIN: C-229T; THBS1: T+42C; LTBP1L: C-256G; LTBP4: T-893G and Thr750Ala; BAMBI: T-779A) were selected for genotyping. We evaluated the associations between genotypes and CRC and Dukes' stage. Survival probabilities were compared between different subgroups. The observed statistically significant associations included a decreased CRC risk for TGFBR1 IVS7G+24A minor allele carriers (odds ratio (OR): 0.72, 95% confidence interval (CI): 0.53-0.97), less aggressive tumors with Dukes' stage A+B for carriers of LTBP4 Thr750Ala and BAMBI T-779A minor alleles (OR: 0.58, 95%CI: 0.36-0.93 and OR: 0.51, 95%CI: 0.29-0.89, respectively) and worse survival for FURIN C-229T heterozygotes (hazard ratio: 1.63, 95%CI: 1.08-2.46). As this is the first study about the influence of the polymorphisms in the TGFB1 pathway on CRC progression, further studies in large independent cohorts are warranted.

Place, publisher, year, edition, pages
New York: Liss , 2010. Vol. 49, no 3, 270-281 p.
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Cancer and Oncology Nutrition and Dietetics Nursing Family Medicine
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URN: urn:nbn:se:umu:diva-31189DOI: 10.1002/gcc.20738ISI: 000273929200008PubMedID: 19998449OAI: oai:DiVA.org:umu-31189DiVA: diva2:291696
Available from: 2010-02-03 Created: 2010-02-03 Last updated: 2015-04-22Bibliographically approved

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Tavelin, BjörnEnquist, KerstinPalmqvist, RichardHallmans, GöranLenner, Per

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