title: IGF1 gene polymorphism and risk for hereditary nonpolyposis colorectal cancer.
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(< or = 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.
authors.affiliation: Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Maja
authors.initials: M
authors.lastname: Zecevic
authors.forename: Christopher I
authors.initials: CI
authors.lastname: Amos
authors.forename: Xiangjun
authors.initials: X
authors.lastname: Gu
authors.forename: Imelda M
authors.initials: IM
authors.lastname: Campos
authors.forename: J Shawn
authors.initials: JS
authors.lastname: Jones
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Lynch
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Rodriguez-Bigas
authors.forename: Marsha L
authors.initials: ML
authors.lastname: Frazier
mesh_terms: D000225:Adenine; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D016001:Confidence Intervals; D003596:Cytosine; D005260:Female; D019940:Genes, bcl-1; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D016016:Proportional Hazards Models; D012107:Research Design; D012307:Risk Factors; D016019:Survival Analysis
chemical_list: D007334:Insulin-Like Growth Factor I; D003596:Cytosine; D000225:Adenine