title: Genomic copy number of a carcinogenic single nucleotide polymorphism at 8q24 in non-risk allele colorectal cancer associated with insulin growth factor 2 receptor expression.
abstract: OBJECTIVE
  The incidence of both diabetes mellitus and hyperlipidemia is increasing and they are risk factors for colorectal cancer (CRC). On the other hand, the carcinogenic significance of the single nucleotide polymorphism (SNP), rs6983267 at 8q24, in CRC has been reported. The association between the SNP genotype and genes associated with diabetes or hyperlipidemia was investigated in cases of CRC.
  
  
  METHODS
  In 107 cases of CRC diagnosed in eight institutes from 2003 to 2008, array-CGH and cDNA microarray was performed and the data analyzed from two groups subdivided according to SNP genotype.
  
  
  RESULTS
  In the array-CGH data, we selected 38 genes related to diabetes or fat metabolism, and of these 10 had a correlation coefficient between the genome copy number at 8q24 locus and that of each gene. Of the 10 genes, insulin growth factor 2 receptor (IGF2R) was the only one with an expression level significantly associated with the 8q24 genotype. IGF2R expression was significantly lower in non-risk allele than in risk allele cases (P = 0.012). There was neither a diabetes- nor a fat metabolism-related gene that was significantly associated with CRC cases with the risk allele at 8q24.
  
  
  CONCLUSIONS
  SNP at 8q24 makes diabetes a risk factor of CRC via IGF2R, especially in genetically non-risk allele cases. We speculate that the risk allele of 8q24 might be risky enough that diabetes is not necessary to worsen the risk for CRC.
authors.affiliation: Department of Surgical Oncology, Medical Institute of Bioregulation, Kyushu University, Beppu, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Koshi
authors.initials: K
authors.lastname: Mimori
authors.forename: Ken
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Tanaka
authors.forename: Shin-Ei
authors.initials: SE
authors.lastname: Kudo
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Sugihara
authors.forename: Kazuo
authors.initials: K
authors.lastname: Hase
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Mochizuki
authors.forename: Masato
authors.initials: M
authors.lastname: Kusunoki
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Yamada
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Shimada
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Moriya
authors.forename: Masaki
authors.initials: M
authors.lastname: Mori
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D003920:Diabetes Mellitus / Q000453:epidemiology / Q000235:genetics*; D015536:Down-Regulation; D005260:Female; D018628:Gene Dosage; D020869:Gene Expression Profiling / Q000379:methods; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D006949:Hyperlipidemias / Q000453:epidemiology / Q000235:genetics*; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D017527:Receptor, IGF Type 2 / Q000235:genetics*; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D017527:Receptor, IGF Type 2