A new single nucleotide polymorphism in the insulin-like growth factor I regulatory region associates with colorectal cancer risk in singapore chinese.
Elevated levels of plasma insulin-like growth factor I (IGF-I) are a potential risk factor for several cancers, including colorectal cancer. Physiologic levels of plasma IGF-I vary greatly; this variation may be in part genetically determined. We identified two single nucleotide polymorphisms (SNP) in perfect linkage disequilibrium with each other and in partial linkage disequilibrium with a previously studied cytosine-adenine microsatellite [-969(CA)(n)]. We investigated one of the SNPs, -533T/C,and the 969(CA)(n) in relation to the risk of colorectal cancer in a case-control study nested within a cohort of Singapore Chinese (cases/controls = 290:873). The (CA)(21) allele, rather than the previously implicated (CA)(19) allele, was associated with a reduced risk of colorectal cancer (odds ratio for 21/21 versus all other genotypes, 0.48; 95% confidence interval, 0.28-0.84). For the -533C/T SNP, persons carrying one or more copies of the C allele had a decreased in risk of colorectal cancer compared with noncarriers (odds ratio for CC/CT versus TT, 0.58; 95% confidence interval, 0.41-0.82). This association was specific for colon, as opposed to rectal cancer and was modified by age. We also examined a functional insulin-like growth factor binding protein (IGFBP3) promoter SNP, -202 A/C, previously reported to predict serum IGFBP3 levels. Although we were able to confirm this genotype-phenotype association, the -202A/C IGFBP3 SNP was not significantly associated with colorectal cancer risk. In conclusion, we report a novel SNP in the IGF-I regulatory region that is associated with colorectal cancer risk.
Wong
Hui-Lee
HL
University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA 90089, USA.
Delellis
Katherine
K
Probst-Hensch
Nicole
N
Koh
Woon-Puay
WP
Van Den Berg
David
D
Lee
Hin-Peng
HP
Yu
Mimi C
MC
Ingles
Sue A
SA
D000483:Alleles; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002648:Child; D002681:China / Q000208:ethnology; D015179:Colorectal Neoplasms / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005828:Genetics, Population; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D015810:Linkage Disequilibrium; D018895:Microsatellite Repeats / Q000235:genetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D011446:Prospective Studies; D012044:Regression Analysis; D012307:Risk Factors; D012846:Singapore / Q000453:epidemiology
D007334:Insulin-Like Growth Factor I