Beyond GWAS of Colorectal Cancer: Evidence of Interaction with Alcohol Consumption and Putative Causal Variant for the 10q24.2 Region

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378041%3A_____%2F22%3A00568390" target="_blank" >RIV/68378041:_____/22:00568390 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11110/22:10444942 RIV/00216208:11140/22:10444942

Výsledek na webu

<a href="https://aacrjournals.org/cebp/article-abstract/31/5/1077/694750/Beyond-GWAS-of-Colorectal-Cancer-Evidence-of?redirectedFrom=fulltext" target="_blank" >https://aacrjournals.org/cebp/article-abstract/31/5/1077/694750/Beyond-GWAS-of-Colorectal-Cancer-Evidence-of?redirectedFrom=fulltext</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1158/1055-9965.EPI-21-1003" target="_blank" >10.1158/1055-9965.EPI-21-1003</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Beyond GWAS of Colorectal Cancer: Evidence of Interaction with Alcohol Consumption and Putative Causal Variant for the 10q24.2 Region

Popis výsledku v původním jazyce

Background: Currently known associations between common genetic variants and colorectal cancer explain less than half of its heritability of 25%. As alcohol consumption has a J-shape associ-ation with colorectal cancer risk, nondrinking and heavy drinking are both risk factors for colorectal cancer.nnMethods: Individual-level data was pooled from the Colon Cancer Family Registry, Colorectal Transdisciplinary Study, and Genetics and Epidemiology of Colorectal Cancer Consortium to compare nondrinkers (<= 1 g/day) and heavy drinkers (>28 g/day) with light-to-moderate drinkers (1-28 g/day) in GxE analyses. To improve power, we implemented joint 2df and 3df tests anda novel two-step method that modifies the weighted hypothesis testing framework. We prioritized putative causal variants by predicting allelic effects using support vector machine models.nnResults: For nondrinking as compared with light-to-moderate drinking, the hybrid two-step approach identified 13 significant SNPs with pairwise r(2) > 0.9 in the 10q24.2/COX15 region. When stratified by alcohol intake, the A allele of lead SNP rs2300985 has a dose-response increase in risk of colorectal cancer as compared with the G allele in light-to-moderate drinkers [OR for GA genotype = 1.11, 95% confidence interval (CI), 1.06-1.17, OR for AA genotype = 1.22, 95% CI, 1.14-1.31], but not in non-drinkers or heavy drinkers. Among the correlated candidate SNPs in the 10q24.2/COX15 region, rs1318920 was predicted to disrupt an HNF4 transcription factor binding motif.nnConclusions: Our study suggests that the association with colorectal cancer in 10q24.2/COX15 observed in genome-wide association study is strongest in nondrinkers. We also identified rs1318920 as the putative causal regulatory variant for the region.nnImpact: The study identifies multifaceted evidence of a possible functional effect for rs1318920.

Název v anglickém jazyce

Beyond GWAS of Colorectal Cancer: Evidence of Interaction with Alcohol Consumption and Putative Causal Variant for the 10q24.2 Region

Popis výsledku anglicky

Background: Currently known associations between common genetic variants and colorectal cancer explain less than half of its heritability of 25%. As alcohol consumption has a J-shape associ-ation with colorectal cancer risk, nondrinking and heavy drinking are both risk factors for colorectal cancer.nnMethods: Individual-level data was pooled from the Colon Cancer Family Registry, Colorectal Transdisciplinary Study, and Genetics and Epidemiology of Colorectal Cancer Consortium to compare nondrinkers (<= 1 g/day) and heavy drinkers (>28 g/day) with light-to-moderate drinkers (1-28 g/day) in GxE analyses. To improve power, we implemented joint 2df and 3df tests anda novel two-step method that modifies the weighted hypothesis testing framework. We prioritized putative causal variants by predicting allelic effects using support vector machine models.nnResults: For nondrinking as compared with light-to-moderate drinking, the hybrid two-step approach identified 13 significant SNPs with pairwise r(2) > 0.9 in the 10q24.2/COX15 region. When stratified by alcohol intake, the A allele of lead SNP rs2300985 has a dose-response increase in risk of colorectal cancer as compared with the G allele in light-to-moderate drinkers [OR for GA genotype = 1.11, 95% confidence interval (CI), 1.06-1.17, OR for AA genotype = 1.22, 95% CI, 1.14-1.31], but not in non-drinkers or heavy drinkers. Among the correlated candidate SNPs in the 10q24.2/COX15 region, rs1318920 was predicted to disrupt an HNF4 transcription factor binding motif.nnConclusions: Our study suggests that the association with colorectal cancer in 10q24.2/COX15 observed in genome-wide association study is strongest in nondrinkers. We also identified rs1318920 as the putative causal regulatory variant for the region.nnImpact: The study identifies multifaceted evidence of a possible functional effect for rs1318920.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10603 - Genetics and heredity (medical genetics to be 3)

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2022

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Cancer Epidemiology Biomarkers & Prevention

ISSN

1055-9965

e-ISSN

1538-7755

Svazek periodika

31

Číslo periodika v rámci svazku

5

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

13

Strana od-do

1077-1089

Kód UT WoS článku

000796705300001

EID výsledku v databázi Scopus

2-s2.0-85129781310