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Polymorphisms in the Transforming Growth Factor Beta 1 Pathway in Relation to Colorectal Cancer Progression

Foersti, Asta; Li, Xuchen; Wagner, Kerstin; Tavelin, Bjorn; Enquist, Kerstin; Palmqvist, Richard; Altieri, Andrea; Hallmans, Goran; Hemminki, Kari LU and Lenner, Per (2010) In Genes, Chromosomes and Cancer 49(3). p.270-281
Abstract
Transforming growth factor beta 1 (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;... (More)
Transforming growth factor beta 1 (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; BAMB1: 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 BAMB1 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 TGFBI pathway on CRC progression, further studies in large independent cohorts are warranted. (C) 2009 Wiley-Liss, Inc. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Genes, Chromosomes and Cancer
volume
49
issue
3
pages
270 - 281
publisher
John Wiley & Sons
external identifiers
  • wos:000273929200008
  • scopus:76649140506
ISSN
1045-2257
DOI
10.1002/gcc.20738
language
English
LU publication?
yes
id
b492b3f8-7326-4b50-888b-23164bb8120d (old id 1547308)
date added to LUP
2010-02-24 09:33:21
date last changed
2018-05-29 10:32:50
@article{b492b3f8-7326-4b50-888b-23164bb8120d,
  abstract     = {Transforming growth factor beta 1 (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; BAMB1: 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 BAMB1 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 TGFBI pathway on CRC progression, further studies in large independent cohorts are warranted. (C) 2009 Wiley-Liss, Inc.},
  author       = {Foersti, Asta and Li, Xuchen and Wagner, Kerstin and Tavelin, Bjorn and Enquist, Kerstin and Palmqvist, Richard and Altieri, Andrea and Hallmans, Goran and Hemminki, Kari and Lenner, Per},
  issn         = {1045-2257},
  language     = {eng},
  number       = {3},
  pages        = {270--281},
  publisher    = {John Wiley & Sons},
  series       = {Genes, Chromosomes and Cancer},
  title        = {Polymorphisms in the Transforming Growth Factor Beta 1 Pathway in Relation to Colorectal Cancer Progression},
  url          = {http://dx.doi.org/10.1002/gcc.20738},
  volume       = {49},
  year         = {2010},
}