A two-phase case-control study for colorectal cancer genetic susceptibility: candidate genes from chromosomal regions 9q22 and 3q22

Br J Cancer. 2011 Sep 6;105(6):870-5. doi: 10.1038/bjc.2011.296. Epub 2011 Aug 2.


Background: Colorectal cancer (CRC) is the second cause of cancer-related death in the Western world. Much of the CRC genetic risk remains unidentified and may be attributable to a large number of common, low-penetrance genetic variants. Genetic linkage studies in CRC families have reported additional association with regions 9q22-31, 3q21-24, 7q31, 11q, 14q and 22q. There are several plausible candidate genes for CRC susceptibility within the aforementioned linkage regions including PTCH1, XPA and TGFBR1 in 9q22-31, and EPHB1 and MRAS in 3q21-q24.

Methods: CRC cases and matched controls were from EPICOLON, a prospective, multicentre, nationwide Spanish initiative, composed of two independent phases. Phase 1 corresponded to 515 CRC cases and 515 controls, whereas phase 2 consisted of 901 CRC cases and 909 controls. Genotyping was performed for 172 single-nucleotide polymorphisms (SNPs) in 84 genes located within regions 9q22-31 and 3q21-q24.

Results: None of the 172 SNPs analysed in our study could be formally associated with CRC risk. However, rs1444601 (TOPBP1) and rs13088006 (CDV3) in region 3q22 showed interesting results and may have an effect on CRC risk.

Conclusions: TOPBP1 and CDV3 genetic variants on region 3q22 may modulate CRC risk. Further validation and meta-analysis should be undertaken in larger CRC cohorts.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antigens, CD / genetics
  • Carrier Proteins / genetics
  • Case-Control Studies
  • Chromosomes, Human, Pair 3*
  • Chromosomes, Human, Pair 9*
  • Colorectal Neoplasms / genetics*
  • DNA-Binding Proteins / genetics
  • GPI-Linked Proteins / genetics
  • Genetic Association Studies
  • Genetic Predisposition to Disease*
  • Humans
  • Male
  • Nuclear Proteins / genetics
  • Polymorphism, Single Nucleotide
  • Semaphorins / genetics


  • Antigens, CD
  • Carrier Proteins
  • DNA-Binding Proteins
  • GPI-Linked Proteins
  • Nuclear Proteins
  • SEMA7A protein, human
  • Semaphorins
  • TOPBP1 protein, human