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- Title
IGF1 Gene Polymorphism and Risk for Hereditary Nonpolyposis Colorectal Cancer.
- Authors
Zecevic, Maja; Amos, Christopher I.; Xiangjun Gu; Campos, Imelda M.; Jones, J. Shawn; Lynch, Patrick M.; Rodriguez-Bigas, Miguel A.; Frazier, Marsha L.
- Abstract
Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant disorder caused by germline mutations in DNA mismatch repair (MMR) genes. Insulin-like growth factor-I (IGF-I) is involved in colorectal carcinogenesis, and elevated plasma IGF-I levels are associated with sporadic colorectal cancer (CRC) risk. We investigated the relationship between IGF1 promoter cytosine-adenine (CA) dinucleotide-repeat polymorphism length and CRC risk in 121 MMR gene mutation carriers using Cox regression and Kaplan-Meier analysis. All statistical tests were two-sided. Time to onset for CRC increased for each decrease in CA-repeat number (median = 19 repeats, range = 12–22 repeats; hazard ratio [HR] = 1.17, 95% confidence interval [CI] = 1.05 to 1.31; P = .006). Patients carrying a CA≤17 repeat allele had a statistically significantly higher CRC risk (HR = 2.36; 95% CI = 1.28 to 4.36; P = .006) than all others and were younger at onset (44 years versus 56.5 years; P =.023). These findings indicate a statistically significant association between shorter IGF1 CA-repeat lengths and increased risk for CRC in HNPCC. This is the first report, to our knowledge, to show that IGF1 variant genotypes modify risk of a hereditary form of cancer.
- Subjects
GENETIC polymorphisms; COLON cancer; GENETIC disorders; HEREDITY; SOMATOMEDIN; GROWTH factors
- Publication
JNCI: Journal of the National Cancer Institute, 2006, Vol 98, Issue 2, p139
- ISSN
0027-8874
- Publication type
Article
- DOI
10.1093/jnci/djj016