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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
Jazyk angličtina Země Anglie, Velká Británie
Typ dokumentu práce podpořená grantem
Grantová podpora
NR8563
MZ0
CEP - Centrální evidence projektů
Digitální knihovna NLK
Plný text - Část
Zdroj
NLK
Free Medical Journals
od 1998 do Před 1 rokem
Open Access Digital Library
od 1994-03-01
Open Access Digital Library
od 1998-01-01
PubMed
17914103
Knihovny.cz E-zdroje
- MeSH
- CD antigeny * genetika metabolismus MeSH
- dospělí MeSH
- fosfoproteiny genetika MeSH
- genetická predispozice k nemoci MeSH
- inzulin genetika metabolismus MeSH
- jednonukleotidový polymorfismus * fyziologie MeSH
- karcinom * genetika MeSH
- kolorektální nádory * genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- promotorové oblasti (genetika) * MeSH
- proteiny insulinového receptorového substrátu MeSH
- receptor inzulinu * genetika metabolismus MeSH
- rizikové faktory MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- signální transdukce * genetika MeSH
- studie případů a kontrol MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- práce podpořená grantem 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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