Abstract
Genome-wide association studies (GWAS) in colorectal cancer (CRC) identified five regions near transforming growth factor ß-related genes BMP4, GREM1, CDH1, SMAD7 and RPHN2. The true risk alleles remain to be identified in these regions, and their role in CRC risk in non-European populations has been understudied. Our previous work noted significant genetic heterogeneity between African Americans (AAs) and European Americans (EAs) for single nucleotide polymorphisms (SNPs) identified in GWAS. We hypothesized that associations may not have been replicated in AAs due to differential or independent genetic structures. In order to test this hypothesis, we genotyped 195 tagging SNPs across these five gene regions in 1194 CRC cases (795 AAs and 399 EAs) and 1352 controls (985 AAs and 367 EAs). Imputation was performed, and association testing of genotyped and imputed SNPs included ancestry, age and sex as covariates. In two of the five genes originally associated with CRC, we found evidence for association in AAs including rs1862748 in CDH1 (ORAdd = 0.82, P = 0.02) and in GREM1 the SNPs rs10318 (ORRec = 60.1, P = 0.01), rs11632715 (ORRec = 2.36; P = 0.004) and rs12902616 (ORRec = 1.28, P = 0.005), the latter which is in linkage disequilibrium with the previously identified SNP rs4779584. Testing more broadly for associations in these gene regions in AAs, we noted three statistically significant association peaks in GREM1 and RHPN2 that were not identified in EAs. We conclude that some CRC risk alleles are shared between EAs and AAs and others are population specific.
| Original language | English (US) |
|---|---|
| Article number | bgu088 |
| Pages (from-to) | 2025-2030 |
| Number of pages | 6 |
| Journal | Carcinogenesis |
| Volume | 35 |
| Issue number | 9 |
| DOIs | |
| State | Published - 2014 |
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ASJC Scopus subject areas
- Cancer Research
Cite this
Shared and independent colorectal cancer risk alleles in TGFß-related genes in African and European Americans. / Kupfer, Sonia S.; Skol, Andrew D.; Hong, Ellie; Ludvik, Anton; Kittles, Rick A; Keku, Temitope O.; Sandler, Robert S.; Ellis, Nathan.
In: Carcinogenesis, Vol. 35, No. 9, bgu088, 2014, p. 2025-2030.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Shared and independent colorectal cancer risk alleles in TGFß-related genes in African and European Americans
AU - Kupfer, Sonia S.
AU - Skol, Andrew D.
AU - Hong, Ellie
AU - Ludvik, Anton
AU - Kittles, Rick A
AU - Keku, Temitope O.
AU - Sandler, Robert S.
AU - Ellis, Nathan
PY - 2014
Y1 - 2014
N2 - Genome-wide association studies (GWAS) in colorectal cancer (CRC) identified five regions near transforming growth factor ß-related genes BMP4, GREM1, CDH1, SMAD7 and RPHN2. The true risk alleles remain to be identified in these regions, and their role in CRC risk in non-European populations has been understudied. Our previous work noted significant genetic heterogeneity between African Americans (AAs) and European Americans (EAs) for single nucleotide polymorphisms (SNPs) identified in GWAS. We hypothesized that associations may not have been replicated in AAs due to differential or independent genetic structures. In order to test this hypothesis, we genotyped 195 tagging SNPs across these five gene regions in 1194 CRC cases (795 AAs and 399 EAs) and 1352 controls (985 AAs and 367 EAs). Imputation was performed, and association testing of genotyped and imputed SNPs included ancestry, age and sex as covariates. In two of the five genes originally associated with CRC, we found evidence for association in AAs including rs1862748 in CDH1 (ORAdd = 0.82, P = 0.02) and in GREM1 the SNPs rs10318 (ORRec = 60.1, P = 0.01), rs11632715 (ORRec = 2.36; P = 0.004) and rs12902616 (ORRec = 1.28, P = 0.005), the latter which is in linkage disequilibrium with the previously identified SNP rs4779584. Testing more broadly for associations in these gene regions in AAs, we noted three statistically significant association peaks in GREM1 and RHPN2 that were not identified in EAs. We conclude that some CRC risk alleles are shared between EAs and AAs and others are population specific.
AB - Genome-wide association studies (GWAS) in colorectal cancer (CRC) identified five regions near transforming growth factor ß-related genes BMP4, GREM1, CDH1, SMAD7 and RPHN2. The true risk alleles remain to be identified in these regions, and their role in CRC risk in non-European populations has been understudied. Our previous work noted significant genetic heterogeneity between African Americans (AAs) and European Americans (EAs) for single nucleotide polymorphisms (SNPs) identified in GWAS. We hypothesized that associations may not have been replicated in AAs due to differential or independent genetic structures. In order to test this hypothesis, we genotyped 195 tagging SNPs across these five gene regions in 1194 CRC cases (795 AAs and 399 EAs) and 1352 controls (985 AAs and 367 EAs). Imputation was performed, and association testing of genotyped and imputed SNPs included ancestry, age and sex as covariates. In two of the five genes originally associated with CRC, we found evidence for association in AAs including rs1862748 in CDH1 (ORAdd = 0.82, P = 0.02) and in GREM1 the SNPs rs10318 (ORRec = 60.1, P = 0.01), rs11632715 (ORRec = 2.36; P = 0.004) and rs12902616 (ORRec = 1.28, P = 0.005), the latter which is in linkage disequilibrium with the previously identified SNP rs4779584. Testing more broadly for associations in these gene regions in AAs, we noted three statistically significant association peaks in GREM1 and RHPN2 that were not identified in EAs. We conclude that some CRC risk alleles are shared between EAs and AAs and others are population specific.
UR - http://www.scopus.com/inward/record.url?scp=84906827625&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84906827625&partnerID=8YFLogxK
U2 - 10.1093/carcin/bgu088
DO - 10.1093/carcin/bgu088
M3 - Article
C2 - 24753543
AN - SCOPUS:84906827625
VL - 35
SP - 2025
EP - 2030
JO - Carcinogenesis
JF - Carcinogenesis
SN - 0143-3334
IS - 9
M1 - bgu088
ER -