Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Försti, A. et al.

Asta Försti, Xuchen Li, Kerstin Wagner, Björn Tavelin, Kerstin Enquist, Richard Palmqvist, Andrea Altieri, Göran Hallmans, Kari Hemminki, Per Lenner,

Polymorphisms in the transforming growth factor beta 1 pathway in relation to colorectal cancer progression.

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.[1]

References

Polymorphisms in the transforming growth factor beta 1 pathway in relation to colorectal cancer progression. Försti, A., Li, X., Wagner, K., Tavelin, B., Enquist, K., Palmqvist, R., Altieri, A., Hallmans, G., Hemminki, K., Lenner, P. Genes. Chromosomes. Cancer (2010) [Pubmed]

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