Generalizability and epidemiologic characterization of eleven colorectal cancer GWAS hits in multiple populations.
BACKGROUND
Genome-wide association studies (GWAS) in populations of European ancestry have identified several loci that confer an increased risk of colorectal cancer (CRC).


METHODS
We studied the generalizability of the associations with 11 risk variants for CRC on 8q23 (rs16892766), 8q24 (rs6983267), 9p24 (rs719725), 10p14 (rs10795668), 11q23 (rs3802842), 14q22 (rs4444235), 15q13 (rs4779584), 16q22 (rs9929218), 18q21 (rs4939827), 19q13 (rs10411210), and 20p12 (rs961253) in a multiethnic sample of 2,472 CRC cases, 839 adenoma cases and 4,466 controls comprised of European American, African American, Native Hawaiian, Japanese American, and Latino men and women. Because findings for CRC and adenoma were similar, we combined both groups in the analyses.


RESULTS
We confirmed the associations with an increased risk of CRC/adenoma for the 8q24, 11q23 and 15q13 loci in European Americans, and observed significant associations between the 8q24 and 20p12 loci with CRC/adenoma risk in African Americans. Moreover, we found statistically significant cumulative effects of risk alleles on CRC/adenoma risk in all populations (odds ratio [OR] per allele = 1.07-1.09, P ≤ 0.039) except in Japanese Americans (OR = 1.01, P = 0.52). We found heterogeneity in the associations by tumor subsite, age of CRC/adenoma onset, sex, body mass index (BMI), and smoking status for some of the variants.


CONCLUSIONS
These results provide evidence that the known variants are in aggregate significantly associated with CRC/adenoma risk in multiple populations except Japanese Americans, and the influences may differ across groups defined by clinicopathological characteristics for some variants.


CONCLUSIONS
These results underline the importance of studying the epidemiologic architecture of these genetic effects in large and diverse populations.
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, USC/Norris Comprehensive Cancer Center, Harlyne Norris Research Tower, 1450 Biggy Street, Los Angeles, CA 90033, USA.
Jing
J
He
Lynne R
LR
Wilkens
Daniel O
DO
Stram
Laurence N
LN
Kolonel
Brian E
BE
Henderson
Anna H
AH
Wu
Loic
L
Le Marchand
Christopher A
CA
Haiman
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000208:ethnology* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult