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Insulin pathway related genes and risk of colorectal cancer: INSR promoter polymorphism shows a protective effect
Sonali Pechlivanis, Barbara Pardini, Justo Lorenzo Bermejo, Kerstin Wagner, Alessio Naccarati, Ludmila Vodickova, Jan Novotny, Kari Hemminki, Pavel Vodicka, Asta Forsti
Language English Country England, Great Britain
Document type Research Support, Non-U.S. Gov't
Grant support
NR8563
MZ0
CEP Register
Digital library NLK
Full text - Část
Source
NLK
Free Medical Journals
from 1998 to 1 year ago
Open Access Digital Library
from 1994-03-01
Open Access Digital Library
from 1998-01-01
PubMed
17914103
Knihovny.cz E-resources
- MeSH
- Antigens, CD * genetics metabolism MeSH
- Adult MeSH
- Phosphoproteins genetics MeSH
- Genetic Predisposition to Disease MeSH
- Insulin genetics metabolism MeSH
- Polymorphism, Single Nucleotide * physiology MeSH
- Carcinoma * genetics MeSH
- Colorectal Neoplasms * genetics MeSH
- Middle Aged MeSH
- Humans MeSH
- Promoter Regions, Genetic * MeSH
- Insulin Receptor Substrate Proteins MeSH
- Receptor, Insulin * genetics metabolism MeSH
- Risk Factors MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Signal Transduction * genetics MeSH
- Case-Control Studies MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
Western lifestyle leading to obesity and type 2 diabetes has been associated with increased risk of colorectal cancer (CRC). Diet and related factors may affect the risk by modifying plasma insulin levels. Thus, the inter-individual variation in insulin signaling may play a plausible role in the development of CRC. We hypothesized that functional polymorphisms in the insulin pathway genes INS, INSR, IGFBPI, insulin receptor substrate 1 (IRS1), and IRS2 may be associated with CRC. We studied the association of five single nucleotide polymorphisms (SNPs) with the risk of CRC using a hospital-based case-control design with 712 cases and 748 controls from the Czech Republic. The INSR A-603G promoter SNP, which is located within a known Sp1-binding site, was associated with the risk of CRC, with carriers of the G allele having a decreased risk (odds ratios (OR) 0.71, 95% confidence interval (CI) 0.54-0.93). Carrying the variant allele of the IRS1 Gly972Arg SNP further decreased the risk among the INSR-603G allele carriers (OR 0.28, 95% CI 0.11-0.70). SNPs in the INS, IGFBPI, and IRS2 genes did not affect the risk of CRC. In conclusion, genetic variation in the insulin signaling pathway genes may affect the risk of CRC.
Literatura
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- $a Pechlivanis, Sonalli $u Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, 69120 Heidelberg, Germany.
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- $a Western lifestyle leading to obesity and type 2 diabetes has been associated with increased risk of colorectal cancer (CRC). Diet and related factors may affect the risk by modifying plasma insulin levels. Thus, the inter-individual variation in insulin signaling may play a plausible role in the development of CRC. We hypothesized that functional polymorphisms in the insulin pathway genes INS, INSR, IGFBPI, insulin receptor substrate 1 (IRS1), and IRS2 may be associated with CRC. We studied the association of five single nucleotide polymorphisms (SNPs) with the risk of CRC using a hospital-based case-control design with 712 cases and 748 controls from the Czech Republic. The INSR A-603G promoter SNP, which is located within a known Sp1-binding site, was associated with the risk of CRC, with carriers of the G allele having a decreased risk (odds ratios (OR) 0.71, 95% confidence interval (CI) 0.54-0.93). Carrying the variant allele of the IRS1 Gly972Arg SNP further decreased the risk among the INSR-603G allele carriers (OR 0.28, 95% CI 0.11-0.70). SNPs in the INS, IGFBPI, and IRS2 genes did not affect the risk of CRC. In conclusion, genetic variation in the insulin signaling pathway genes may affect the risk of CRC.
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