IGF1 gene polymorphism and risk for hereditary nonpolyposis colorectal cancer.

نویسندگان

  • Maja Zecevic
  • Christopher I Amos
  • Xiangjun Gu
  • Imelda M Campos
  • J Shawn Jones
  • Patrick M Lynch
  • Miguel A Rodriguez-Bigas
  • Marsha L Frazier
چکیده

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.

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عنوان ژورنال:
  • Journal of the National Cancer Institute

دوره 98 2  شماره 

صفحات  -

تاریخ انتشار 2006