title: Germline HOXB13 p.Gly84Glu mutation and risk of colorectal cancer.
abstract: BACKGROUND
  The HOXB13 pGly84Glu mutation has recently been associated with an increased risk of prostate cancer but the association of other cancer sites with this allele has not been assessed. Data has suggested that HOXB13 expression levels are decreased in colorectal cancer (CRC) cell lines indicating this gene may be involved in colorectal tumourigenesis.
  
  
  METHODS
  To evaluate a potential association of this mutation with CRC, we genotyped the mutation in 2695 CRC cases and 4593 controls from population-based registries in Canada and Australia.
  
  
  RESULTS
  The HOXB13 pGly84Glu mutation was more common in CRC cases than controls (0.48% vs. 0.17%, P=0.02) indicating a significant association between the HOXB13 variant and CRC risk (OR=2.8; 95%CI: 1.2-6.8). This association was attenuated but remained significant with the inclusion of previously published and publicly available genotype data. Pedigree analysis of cases and controls revealed that 7/21 HOXB13 mutation carriers had a family history of prostate cancer.
  
  
  CONCLUSIONS
  This report is the first to suggest a risk of CRC associated with mutations in the HOXB13 gene. These findings require further validation but may be of importance in the screening and genetic counseling of families known to carry the HOXB13 pGly84Glu mutation.
authors.affiliation: Women's College Research Institute, Women's College Hospital, University of Toronto, Toronto, Canada.
authors.forename: Mohammad R
authors.initials: MR
authors.lastname: Akbari
authors.forename: Laura N
authors.initials: LN
authors.lastname: Anderson
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Buchanan
authors.forename: Mark
authors.initials: M
authors.lastname: Clendenning
authors.forename: Mark A
authors.initials: MA
authors.lastname: Jenkins
authors.forename: Aung Ko
authors.initials: AK
authors.lastname: Win
authors.forename: John L
authors.initials: JL
authors.lastname: Hopper
authors.forename: Graham G
authors.initials: GG
authors.lastname: Giles
authors.forename: Robert
authors.initials: R
authors.lastname: Nam
authors.forename: Steven
authors.initials: S
authors.lastname: Narod
authors.forename: Steven
authors.initials: S
authors.lastname: Gallinger
authors.forename: Sean P
authors.initials: SP
authors.lastname: Cleary
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001315:Australia; D002170:Canada; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018095:Germ-Line Mutation; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012042:Registries; D012306:Risk; D055815:Young Adult
chemical_list: C484414:HOXB13 protein, human; D018398:Homeodomain Proteins
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