Variants on 9p24 and 8q24 are associated with risk of colorectal cancer: results from the Colon Cancer Family Registry.
Recent publications have reported that common variants on 8q24 are associated with both prostate and colorectal cancers (CRC). In addition, one of these studies (the ARCTIC study) initially observed an association with a single nucleotide polymorphism (SNP) on 9p24 that was not confirmed in some of their validation data sets. In the research described here, we conducted a case-unaffected sibling analysis using population- and clinic-based discordant sibships (N = 1,567 sibships) from the Colon Cancer Family Registry (Colon CFR) to investigate the associations between common variants at 9p24 and 8q24 and risk of CRC. We also evaluated whether these associations differed by age, family history, and tumor characteristics, including microsatellite instability and tumor site. Associations were estimated using conditional logistic regression, treating sibship as the matching factor. Analyses were adjusted for age and sex, and stratified by ascertainment source (population versus clinic). We observed an association between a SNP on 9p24 (rs719725) and risk of CRC in the population-based series (AA versus CC: odds ratios, 1.46; 95% confidence interval, 1.06-2.02; AC versus CC: odds ratios, 1.50; 95% confidence interval, 1.14-1.98; P = 0.011 on 2 df). In the population-based series, we also detected statistically significant associations between two SNPs on 8q24, rs10505477 and rs6983267, and risk of CRC (P = 0.005 and P = 0.002, respectively). There was no evidence of statistically significant heterogeneity by age at diagnosis, family history of CRC, microsatellite instability, or tumor site at either locus and no evidence of interaction between SNPs on 8q24 and 9p24. These data suggest that common variants may play important roles in the risk of CRC.
Department of Preventive Medicine, University of Southern California, 1441 Eastlake Avenue, NOR4411A, Los Angeles, CA 90089-9175, USA. poynter@usc.edu
Jenny N
JN
Poynter
Jane C
JC
Figueiredo
David V
DV
Conti
Kathleen
K
Kennedy
Steven
S
Gallinger
Kimberly D
KD
Siegmund
Graham
G
Casey
Stephen N
SN
Thibodeau
Mark A
MA
Jenkins
John L
JL
Hopper
Graham B
GB
Byrnes
John A
JA
Baron
Ellen L
EL
Goode
Maarit
M
Tiirikainen
Noralane
N
Lindor
John
J
Grove
Polly
P
Newcomb
Jeremy
J
Jass
Joanne
J
Young
John D
JD
Potter
Robert W
RW
Haile
David J
DJ
Duggan
Loic
L
Le Marchand
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D017668:Age of Onset; D000368:Aged; D016022:Case-Control Studies; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012042:Registries; D012307:Risk Factors
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein