Polymorphisms in the Transforming Growth Factor Beta 1 Pathway in Relation to Colorectal Cancer Progression
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1547308
- author
- Foersti, Asta ; Li, Xuchen ; Wagner, Kerstin ; Tavelin, Bjorn ; Enquist, Kerstin ; Palmqvist, Richard ; Altieri, Andrea ; Hallmans, Goran ; Hemminki, Kari LU and Lenner, Per
- organization
- publishing date
- 2010
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Genes, Chromosomes and Cancer
- volume
- 49
- issue
- 3
- pages
- 270 - 281
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- wos:000273929200008
- scopus:76649140506
- pmid:19998449
- 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
- 2016-04-01 10:34:56
- date last changed
- 2022-03-27 17:39:30
@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 Inc.}},
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}},
doi = {{10.1002/gcc.20738}},
volume = {{49}},
year = {{2010}},
}