Interaction between polymorphisms in aspirin metabolic pathways, regular aspirin use and colorectal cancer risk: A case-control study in unselected white European populations

Harsh Sheth, Emma Northwood, Cornelia M. Ulrich, Dominique Scherer, Faye Elliott, Jennifer H. Barrett, David Forman, C. Roland Wolf, Gillian Smith, Michael S. Jackson, Mauro Santibanez-Koref, Robert Haile, Graham Casey, Mark Jenkins, Aung Ko Win, John L. Hopper, Loic Le Marchand, Noralane Morey Lindor, Stephen N Thibodeau, John D. PotterJohn Burn, D. Timothy Bishop

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Regular aspirin use is associated with reduced risk of colorectal cancer (CRC). Variation in aspirin's chemoprevention efficacy has been attributed to the presence of single nucleotide polymorphisms (SNPs). We conducted a meta-analysis using two large population-based case-control datasets, the UK-Leeds Colorectal Cancer Study Group and the NIH-Colon Cancer Family Registry, having a combined total of 3325 cases and 2262 controls. The aim was to assess 42 candidate SNPs in 15 genes whose association with colorectal cancer risk was putatively modified by aspirin use, in the literature. Log odds ratios (ORs) and standard errors were estimated for each dataset separately using logistic regression adjusting for age, sex and study site, and dataset-specific results were combined using random effects meta-analysis. Meta-analysis showed association between SNPs rs6983267, rs11694911 and rs2302615 with CRC risk reduction (All P<0.05). Association for SNP rs6983267 in the CCAT2 gene only was noteworthy after multiple test correction (P = 0.001). Site-specific analysis showed association between SNPs rs1799853 and rs2302615 with reduced colon cancer risk only (P = 0.01 and P = 0.004, respectively), however neither reached significance threshold following multiple test correction. Meta-analysis of SNPs rs2070959 and rs1105879 in UGT1A6 gene showed interaction between aspirin use and CRC risk (Pinteraction = 0.01 and 0.02, respectively); stratification by aspirin use showed an association for decreased CRC risk for aspirin users having a wild-type genotype (rs2070959 OR = 0.77, 95% CI = 0.68±0.86; rs1105879 OR = 0.77 95% CI = 0.69 0.86) compared to variant allele cariers. The direction of the interaction however is in contrast to that published in studies on colorectal adenomas. Both SNPs showed potential site-specific interaction with aspirin use and colon cancer risk only (Pinteraction = 0.006 and 0.008, respectively), with the direction of association similar to that observed for CRC. Additionally, they showed interaction between any non-steroidal anti-inflammatory drugs (including aspirin) use and CRC risk (Pinteraction = 0.01 for both). All gene x environment (GxE) interactions however were not significant after multiple test correction. Candidate gene investigation indicated no evidence of GxE interaction between genetic variants in genes involved in aspirin pathways, regular aspirin use and colorectal cancer risk.

Original languageEnglish (US)
Article numbere0192223
JournalPLoS One
Volume13
Issue number2
DOIs
StatePublished - Feb 1 2018

Fingerprint

aspirin
Metabolic Networks and Pathways
case-control studies
Polymorphism
colorectal neoplasms
Aspirin
biochemical pathways
Case-Control Studies
Colorectal Neoplasms
genetic polymorphism
Single Nucleotide Polymorphism
Nucleotides
Genes
single nucleotide polymorphism
Population
Association reactions
Meta-Analysis
meta-analysis
Colonic Neoplasms
Gene-Environment Interaction

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Interaction between polymorphisms in aspirin metabolic pathways, regular aspirin use and colorectal cancer risk : A case-control study in unselected white European populations. / Sheth, Harsh; Northwood, Emma; Ulrich, Cornelia M.; Scherer, Dominique; Elliott, Faye; Barrett, Jennifer H.; Forman, David; Roland Wolf, C.; Smith, Gillian; Jackson, Michael S.; Santibanez-Koref, Mauro; Haile, Robert; Casey, Graham; Jenkins, Mark; Win, Aung Ko; Hopper, John L.; Le Marchand, Loic; Lindor, Noralane Morey; Thibodeau, Stephen N; Potter, John D.; Burn, John; Timothy Bishop, D.

In: PLoS One, Vol. 13, No. 2, e0192223, 01.02.2018.

Research output: Contribution to journalArticle

Sheth, H, Northwood, E, Ulrich, CM, Scherer, D, Elliott, F, Barrett, JH, Forman, D, Roland Wolf, C, Smith, G, Jackson, MS, Santibanez-Koref, M, Haile, R, Casey, G, Jenkins, M, Win, AK, Hopper, JL, Le Marchand, L, Lindor, NM, Thibodeau, SN, Potter, JD, Burn, J & Timothy Bishop, D 2018, 'Interaction between polymorphisms in aspirin metabolic pathways, regular aspirin use and colorectal cancer risk: A case-control study in unselected white European populations', PLoS One, vol. 13, no. 2, e0192223. https://doi.org/10.1371/journal.pone.0192223
Sheth, Harsh ; Northwood, Emma ; Ulrich, Cornelia M. ; Scherer, Dominique ; Elliott, Faye ; Barrett, Jennifer H. ; Forman, David ; Roland Wolf, C. ; Smith, Gillian ; Jackson, Michael S. ; Santibanez-Koref, Mauro ; Haile, Robert ; Casey, Graham ; Jenkins, Mark ; Win, Aung Ko ; Hopper, John L. ; Le Marchand, Loic ; Lindor, Noralane Morey ; Thibodeau, Stephen N ; Potter, John D. ; Burn, John ; Timothy Bishop, D. / Interaction between polymorphisms in aspirin metabolic pathways, regular aspirin use and colorectal cancer risk : A case-control study in unselected white European populations. In: PLoS One. 2018 ; Vol. 13, No. 2.
@article{89b3f8613604498aa2434b913dcbb2ea,
title = "Interaction between polymorphisms in aspirin metabolic pathways, regular aspirin use and colorectal cancer risk: A case-control study in unselected white European populations",
abstract = "Regular aspirin use is associated with reduced risk of colorectal cancer (CRC). Variation in aspirin's chemoprevention efficacy has been attributed to the presence of single nucleotide polymorphisms (SNPs). We conducted a meta-analysis using two large population-based case-control datasets, the UK-Leeds Colorectal Cancer Study Group and the NIH-Colon Cancer Family Registry, having a combined total of 3325 cases and 2262 controls. The aim was to assess 42 candidate SNPs in 15 genes whose association with colorectal cancer risk was putatively modified by aspirin use, in the literature. Log odds ratios (ORs) and standard errors were estimated for each dataset separately using logistic regression adjusting for age, sex and study site, and dataset-specific results were combined using random effects meta-analysis. Meta-analysis showed association between SNPs rs6983267, rs11694911 and rs2302615 with CRC risk reduction (All P<0.05). Association for SNP rs6983267 in the CCAT2 gene only was noteworthy after multiple test correction (P = 0.001). Site-specific analysis showed association between SNPs rs1799853 and rs2302615 with reduced colon cancer risk only (P = 0.01 and P = 0.004, respectively), however neither reached significance threshold following multiple test correction. Meta-analysis of SNPs rs2070959 and rs1105879 in UGT1A6 gene showed interaction between aspirin use and CRC risk (Pinteraction = 0.01 and 0.02, respectively); stratification by aspirin use showed an association for decreased CRC risk for aspirin users having a wild-type genotype (rs2070959 OR = 0.77, 95{\%} CI = 0.68±0.86; rs1105879 OR = 0.77 95{\%} CI = 0.69 0.86) compared to variant allele cariers. The direction of the interaction however is in contrast to that published in studies on colorectal adenomas. Both SNPs showed potential site-specific interaction with aspirin use and colon cancer risk only (Pinteraction = 0.006 and 0.008, respectively), with the direction of association similar to that observed for CRC. Additionally, they showed interaction between any non-steroidal anti-inflammatory drugs (including aspirin) use and CRC risk (Pinteraction = 0.01 for both). All gene x environment (GxE) interactions however were not significant after multiple test correction. Candidate gene investigation indicated no evidence of GxE interaction between genetic variants in genes involved in aspirin pathways, regular aspirin use and colorectal cancer risk.",
author = "Harsh Sheth and Emma Northwood and Ulrich, {Cornelia M.} and Dominique Scherer and Faye Elliott and Barrett, {Jennifer H.} and David Forman and {Roland Wolf}, C. and Gillian Smith and Jackson, {Michael S.} and Mauro Santibanez-Koref and Robert Haile and Graham Casey and Mark Jenkins and Win, {Aung Ko} and Hopper, {John L.} and {Le Marchand}, Loic and Lindor, {Noralane Morey} and Thibodeau, {Stephen N} and Potter, {John D.} and John Burn and {Timothy Bishop}, D.",
year = "2018",
month = "2",
day = "1",
doi = "10.1371/journal.pone.0192223",
language = "English (US)",
volume = "13",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "2",

}

TY - JOUR

T1 - Interaction between polymorphisms in aspirin metabolic pathways, regular aspirin use and colorectal cancer risk

T2 - A case-control study in unselected white European populations

AU - Sheth, Harsh

AU - Northwood, Emma

AU - Ulrich, Cornelia M.

AU - Scherer, Dominique

AU - Elliott, Faye

AU - Barrett, Jennifer H.

AU - Forman, David

AU - Roland Wolf, C.

AU - Smith, Gillian

AU - Jackson, Michael S.

AU - Santibanez-Koref, Mauro

AU - Haile, Robert

AU - Casey, Graham

AU - Jenkins, Mark

AU - Win, Aung Ko

AU - Hopper, John L.

AU - Le Marchand, Loic

AU - Lindor, Noralane Morey

AU - Thibodeau, Stephen N

AU - Potter, John D.

AU - Burn, John

AU - Timothy Bishop, D.

PY - 2018/2/1

Y1 - 2018/2/1

N2 - Regular aspirin use is associated with reduced risk of colorectal cancer (CRC). Variation in aspirin's chemoprevention efficacy has been attributed to the presence of single nucleotide polymorphisms (SNPs). We conducted a meta-analysis using two large population-based case-control datasets, the UK-Leeds Colorectal Cancer Study Group and the NIH-Colon Cancer Family Registry, having a combined total of 3325 cases and 2262 controls. The aim was to assess 42 candidate SNPs in 15 genes whose association with colorectal cancer risk was putatively modified by aspirin use, in the literature. Log odds ratios (ORs) and standard errors were estimated for each dataset separately using logistic regression adjusting for age, sex and study site, and dataset-specific results were combined using random effects meta-analysis. Meta-analysis showed association between SNPs rs6983267, rs11694911 and rs2302615 with CRC risk reduction (All P<0.05). Association for SNP rs6983267 in the CCAT2 gene only was noteworthy after multiple test correction (P = 0.001). Site-specific analysis showed association between SNPs rs1799853 and rs2302615 with reduced colon cancer risk only (P = 0.01 and P = 0.004, respectively), however neither reached significance threshold following multiple test correction. Meta-analysis of SNPs rs2070959 and rs1105879 in UGT1A6 gene showed interaction between aspirin use and CRC risk (Pinteraction = 0.01 and 0.02, respectively); stratification by aspirin use showed an association for decreased CRC risk for aspirin users having a wild-type genotype (rs2070959 OR = 0.77, 95% CI = 0.68±0.86; rs1105879 OR = 0.77 95% CI = 0.69 0.86) compared to variant allele cariers. The direction of the interaction however is in contrast to that published in studies on colorectal adenomas. Both SNPs showed potential site-specific interaction with aspirin use and colon cancer risk only (Pinteraction = 0.006 and 0.008, respectively), with the direction of association similar to that observed for CRC. Additionally, they showed interaction between any non-steroidal anti-inflammatory drugs (including aspirin) use and CRC risk (Pinteraction = 0.01 for both). All gene x environment (GxE) interactions however were not significant after multiple test correction. Candidate gene investigation indicated no evidence of GxE interaction between genetic variants in genes involved in aspirin pathways, regular aspirin use and colorectal cancer risk.

AB - Regular aspirin use is associated with reduced risk of colorectal cancer (CRC). Variation in aspirin's chemoprevention efficacy has been attributed to the presence of single nucleotide polymorphisms (SNPs). We conducted a meta-analysis using two large population-based case-control datasets, the UK-Leeds Colorectal Cancer Study Group and the NIH-Colon Cancer Family Registry, having a combined total of 3325 cases and 2262 controls. The aim was to assess 42 candidate SNPs in 15 genes whose association with colorectal cancer risk was putatively modified by aspirin use, in the literature. Log odds ratios (ORs) and standard errors were estimated for each dataset separately using logistic regression adjusting for age, sex and study site, and dataset-specific results were combined using random effects meta-analysis. Meta-analysis showed association between SNPs rs6983267, rs11694911 and rs2302615 with CRC risk reduction (All P<0.05). Association for SNP rs6983267 in the CCAT2 gene only was noteworthy after multiple test correction (P = 0.001). Site-specific analysis showed association between SNPs rs1799853 and rs2302615 with reduced colon cancer risk only (P = 0.01 and P = 0.004, respectively), however neither reached significance threshold following multiple test correction. Meta-analysis of SNPs rs2070959 and rs1105879 in UGT1A6 gene showed interaction between aspirin use and CRC risk (Pinteraction = 0.01 and 0.02, respectively); stratification by aspirin use showed an association for decreased CRC risk for aspirin users having a wild-type genotype (rs2070959 OR = 0.77, 95% CI = 0.68±0.86; rs1105879 OR = 0.77 95% CI = 0.69 0.86) compared to variant allele cariers. The direction of the interaction however is in contrast to that published in studies on colorectal adenomas. Both SNPs showed potential site-specific interaction with aspirin use and colon cancer risk only (Pinteraction = 0.006 and 0.008, respectively), with the direction of association similar to that observed for CRC. Additionally, they showed interaction between any non-steroidal anti-inflammatory drugs (including aspirin) use and CRC risk (Pinteraction = 0.01 for both). All gene x environment (GxE) interactions however were not significant after multiple test correction. Candidate gene investigation indicated no evidence of GxE interaction between genetic variants in genes involved in aspirin pathways, regular aspirin use and colorectal cancer risk.

UR - http://www.scopus.com/inward/record.url?scp=85041919787&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85041919787&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0192223

DO - 10.1371/journal.pone.0192223

M3 - Article

C2 - 29425227

AN - SCOPUS:85041919787

VL - 13

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 2

M1 - e0192223

ER -