Replication and Genetic Risk Score Analysis for Pancreatic Cancer in a Diverse Multiethnic Population.
Journal
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
ISSN: 1538-7755
Titre abrégé: Cancer Epidemiol Biomarkers Prev
Pays: United States
ID NLM: 9200608
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
22
06
2020
revised:
13
08
2020
accepted:
15
09
2020
pubmed:
23
9
2020
medline:
22
12
2021
entrez:
22
9
2020
Statut:
ppublish
Résumé
Genome-wide association studies (GWAS) have identified several SNPs associated with pancreatic cancer. No studies yet have attempted to replicate these SNPs in US minority populations. We aimed to replicate the associations of 31 GWAS-identified SNPs with pancreatic cancer and build and test a polygenic risk score (PRS) for pancreatic cancer in an ethnically diverse population. We evaluated 31 risk variants in the Multiethnic Cohort and the Southern Community Cohort Study. We included 691 pancreatic ductal adenocarcinoma (PDAC) cases and 13,778 controls from African-American, Japanese-American, Latino, Native Hawaiian, and white participants. We tested the association between each SNP and PDAC, established a PRS using the 31 SNPs, and tested the association between the score and PDAC risk. Eleven of the 31 SNPs were replicated in the multiethnic sample. The PRS was associated with PDAC risk [OR top vs. middle quintile = 2.25 (95% confidence interval, 1.73-2.92)]. Notably, the PRS was associated with PDAC risk in all ethnic groups except Native Hawaiian (OR per risk allele ranged from 1.33 in Native Hawaiians to 1.91 in African Americans; This is the first study to replicate 11 of the 31 GWAS-identified risk variants for pancreatic cancer in multiethnic populations, including African Americans, Japanese Americans, and Latinos. Our results also suggest a potential utility of PRS with GWAS-identified risk variants for the identification of individuals at increased risk for PDAC across multiple ethnic groups. PRS can potentially be used to stratify pancreatic cancer risk across multiple ethnic groups.
Sections du résumé
BACKGROUND
Genome-wide association studies (GWAS) have identified several SNPs associated with pancreatic cancer. No studies yet have attempted to replicate these SNPs in US minority populations. We aimed to replicate the associations of 31 GWAS-identified SNPs with pancreatic cancer and build and test a polygenic risk score (PRS) for pancreatic cancer in an ethnically diverse population.
METHODS
We evaluated 31 risk variants in the Multiethnic Cohort and the Southern Community Cohort Study. We included 691 pancreatic ductal adenocarcinoma (PDAC) cases and 13,778 controls from African-American, Japanese-American, Latino, Native Hawaiian, and white participants. We tested the association between each SNP and PDAC, established a PRS using the 31 SNPs, and tested the association between the score and PDAC risk.
RESULTS
Eleven of the 31 SNPs were replicated in the multiethnic sample. The PRS was associated with PDAC risk [OR top vs. middle quintile = 2.25 (95% confidence interval, 1.73-2.92)]. Notably, the PRS was associated with PDAC risk in all ethnic groups except Native Hawaiian (OR per risk allele ranged from 1.33 in Native Hawaiians to 1.91 in African Americans;
CONCLUSIONS
This is the first study to replicate 11 of the 31 GWAS-identified risk variants for pancreatic cancer in multiethnic populations, including African Americans, Japanese Americans, and Latinos. Our results also suggest a potential utility of PRS with GWAS-identified risk variants for the identification of individuals at increased risk for PDAC across multiple ethnic groups.
IMPACT
PRS can potentially be used to stratify pancreatic cancer risk across multiple ethnic groups.
Identifiants
pubmed: 32958499
pii: 1055-9965.EPI-20-0963
doi: 10.1158/1055-9965.EPI-20-0963
pmc: PMC7710597
mid: NIHMS1631275
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2686-2692Subventions
Organisme : NCI NIH HHS
ID : P01 CA236585
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA209798
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA202979
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG007397
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA164973
Pays : United States
Informations de copyright
©2020 American Association for Cancer Research.
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