UGT1A1 and UGT1A9 functional variants, meat intake, and colon cancer, among Caucasians and African-Americans

Hugo Girard, Lesley M. Butler, Lyne Villeneuve, Robert C. Millikan, Rashmi Sinha, Robert S. Sandler, Chantal Guillemette

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Glucuronidation by the UDP-glucuronosyltransferase enzymes (UGTs) is one of the primary detoxification pathways of dietary heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs). In a population-based case-control study of 537 cases and 866 controls, we investigated whether colon cancer was associated with genetic variations in UGT1A1 and UGT1A9 genes and we determined if those variations modify the association between colon cancer and dietary HCA and PAH exposure. We measured functional UGT1A1 polymorphisms at positions -53 (*28; A(TA)6TAA to A(TA)7TAA), -3156 (G > A), -3279 (T > G) and the UGT1A9-275(T > A) polymorphism, and found no association with colon cancer overall. However, when stratified by race, the UGT1A1-3279 GG/TG intermediate/low activity genotypes were associated with an increased risk of colon cancer (odds ratio (OR) = 1.5, 95% confidence interval (CI) = 1.1-2.0) in Caucasians. This finding is also supported by haplotype analyses where the UGT1A1-3279G-allele-bearing haplotype is overrepresented in case group. Overall, UGT1A1-53 and -3156 genotypes modified the association between dietary benzo(a)pyrene (BaP) and colon cancer (P for interaction = 0.02 and 0.03, respectively). The strongest association was observed for those with <7.7 ng/day BaP exposure and the low activity genotypes, for both UGT1A1*28/*28 (OR = 1.8, 95% CI = 1.1-2.9) and -3156AA (OR = 1.7, 95% CI = 1.0-3.0), compared to ≥7.7 ng/day and combined high/intermediate genotypes. These data support a hypothesis that UGTs modify the association between meat-derived PAH exposure and colon cancer by their role in the elimination of dietary carcinogens.

Original languageEnglish (US)
Pages (from-to)56-63
Number of pages8
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume644
Issue number1-2
DOIs
StatePublished - Sep 26 2008

Fingerprint

African Americans
Colonic Neoplasms
Meat
Polycyclic Aromatic Hydrocarbons
Genotype
Odds Ratio
Confidence Intervals
Haplotypes
Amines
Glucuronosyltransferase
Benzo(a)pyrene
Carcinogens
Case-Control Studies
Alleles
Enzymes
Population
Genes

Keywords

  • Amines
  • Colon cancer
  • Genetic
  • Glucuronidation
  • Meat
  • Polymorphism

ASJC Scopus subject areas

  • Health, Toxicology and Mutagenesis
  • Molecular Biology

Cite this

UGT1A1 and UGT1A9 functional variants, meat intake, and colon cancer, among Caucasians and African-Americans. / Girard, Hugo; Butler, Lesley M.; Villeneuve, Lyne; Millikan, Robert C.; Sinha, Rashmi; Sandler, Robert S.; Guillemette, Chantal.

In: Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, Vol. 644, No. 1-2, 26.09.2008, p. 56-63.

Research output: Contribution to journalArticle

Girard, Hugo ; Butler, Lesley M. ; Villeneuve, Lyne ; Millikan, Robert C. ; Sinha, Rashmi ; Sandler, Robert S. ; Guillemette, Chantal. / UGT1A1 and UGT1A9 functional variants, meat intake, and colon cancer, among Caucasians and African-Americans. In: Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis. 2008 ; Vol. 644, No. 1-2. pp. 56-63.
@article{2ee47c3d48024494a23d942d9eca8395,
title = "UGT1A1 and UGT1A9 functional variants, meat intake, and colon cancer, among Caucasians and African-Americans",
abstract = "Glucuronidation by the UDP-glucuronosyltransferase enzymes (UGTs) is one of the primary detoxification pathways of dietary heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs). In a population-based case-control study of 537 cases and 866 controls, we investigated whether colon cancer was associated with genetic variations in UGT1A1 and UGT1A9 genes and we determined if those variations modify the association between colon cancer and dietary HCA and PAH exposure. We measured functional UGT1A1 polymorphisms at positions -53 (*28; A(TA)6TAA to A(TA)7TAA), -3156 (G > A), -3279 (T > G) and the UGT1A9-275(T > A) polymorphism, and found no association with colon cancer overall. However, when stratified by race, the UGT1A1-3279 GG/TG intermediate/low activity genotypes were associated with an increased risk of colon cancer (odds ratio (OR) = 1.5, 95{\%} confidence interval (CI) = 1.1-2.0) in Caucasians. This finding is also supported by haplotype analyses where the UGT1A1-3279G-allele-bearing haplotype is overrepresented in case group. Overall, UGT1A1-53 and -3156 genotypes modified the association between dietary benzo(a)pyrene (BaP) and colon cancer (P for interaction = 0.02 and 0.03, respectively). The strongest association was observed for those with <7.7 ng/day BaP exposure and the low activity genotypes, for both UGT1A1*28/*28 (OR = 1.8, 95{\%} CI = 1.1-2.9) and -3156AA (OR = 1.7, 95{\%} CI = 1.0-3.0), compared to ≥7.7 ng/day and combined high/intermediate genotypes. These data support a hypothesis that UGTs modify the association between meat-derived PAH exposure and colon cancer by their role in the elimination of dietary carcinogens.",
keywords = "Amines, Colon cancer, Genetic, Glucuronidation, Meat, Polymorphism",
author = "Hugo Girard and Butler, {Lesley M.} and Lyne Villeneuve and Millikan, {Robert C.} and Rashmi Sinha and Sandler, {Robert S.} and Chantal Guillemette",
year = "2008",
month = "9",
day = "26",
doi = "10.1016/j.mrfmmm.2008.07.002",
language = "English (US)",
volume = "644",
pages = "56--63",
journal = "Mutation Research",
issn = "0027-5107",
publisher = "Elsevier",
number = "1-2",

}

TY - JOUR

T1 - UGT1A1 and UGT1A9 functional variants, meat intake, and colon cancer, among Caucasians and African-Americans

AU - Girard, Hugo

AU - Butler, Lesley M.

AU - Villeneuve, Lyne

AU - Millikan, Robert C.

AU - Sinha, Rashmi

AU - Sandler, Robert S.

AU - Guillemette, Chantal

PY - 2008/9/26

Y1 - 2008/9/26

N2 - Glucuronidation by the UDP-glucuronosyltransferase enzymes (UGTs) is one of the primary detoxification pathways of dietary heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs). In a population-based case-control study of 537 cases and 866 controls, we investigated whether colon cancer was associated with genetic variations in UGT1A1 and UGT1A9 genes and we determined if those variations modify the association between colon cancer and dietary HCA and PAH exposure. We measured functional UGT1A1 polymorphisms at positions -53 (*28; A(TA)6TAA to A(TA)7TAA), -3156 (G > A), -3279 (T > G) and the UGT1A9-275(T > A) polymorphism, and found no association with colon cancer overall. However, when stratified by race, the UGT1A1-3279 GG/TG intermediate/low activity genotypes were associated with an increased risk of colon cancer (odds ratio (OR) = 1.5, 95% confidence interval (CI) = 1.1-2.0) in Caucasians. This finding is also supported by haplotype analyses where the UGT1A1-3279G-allele-bearing haplotype is overrepresented in case group. Overall, UGT1A1-53 and -3156 genotypes modified the association between dietary benzo(a)pyrene (BaP) and colon cancer (P for interaction = 0.02 and 0.03, respectively). The strongest association was observed for those with <7.7 ng/day BaP exposure and the low activity genotypes, for both UGT1A1*28/*28 (OR = 1.8, 95% CI = 1.1-2.9) and -3156AA (OR = 1.7, 95% CI = 1.0-3.0), compared to ≥7.7 ng/day and combined high/intermediate genotypes. These data support a hypothesis that UGTs modify the association between meat-derived PAH exposure and colon cancer by their role in the elimination of dietary carcinogens.

AB - Glucuronidation by the UDP-glucuronosyltransferase enzymes (UGTs) is one of the primary detoxification pathways of dietary heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs). In a population-based case-control study of 537 cases and 866 controls, we investigated whether colon cancer was associated with genetic variations in UGT1A1 and UGT1A9 genes and we determined if those variations modify the association between colon cancer and dietary HCA and PAH exposure. We measured functional UGT1A1 polymorphisms at positions -53 (*28; A(TA)6TAA to A(TA)7TAA), -3156 (G > A), -3279 (T > G) and the UGT1A9-275(T > A) polymorphism, and found no association with colon cancer overall. However, when stratified by race, the UGT1A1-3279 GG/TG intermediate/low activity genotypes were associated with an increased risk of colon cancer (odds ratio (OR) = 1.5, 95% confidence interval (CI) = 1.1-2.0) in Caucasians. This finding is also supported by haplotype analyses where the UGT1A1-3279G-allele-bearing haplotype is overrepresented in case group. Overall, UGT1A1-53 and -3156 genotypes modified the association between dietary benzo(a)pyrene (BaP) and colon cancer (P for interaction = 0.02 and 0.03, respectively). The strongest association was observed for those with <7.7 ng/day BaP exposure and the low activity genotypes, for both UGT1A1*28/*28 (OR = 1.8, 95% CI = 1.1-2.9) and -3156AA (OR = 1.7, 95% CI = 1.0-3.0), compared to ≥7.7 ng/day and combined high/intermediate genotypes. These data support a hypothesis that UGTs modify the association between meat-derived PAH exposure and colon cancer by their role in the elimination of dietary carcinogens.

KW - Amines

KW - Colon cancer

KW - Genetic

KW - Glucuronidation

KW - Meat

KW - Polymorphism

UR - http://www.scopus.com/inward/record.url?scp=49649083255&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=49649083255&partnerID=8YFLogxK

U2 - 10.1016/j.mrfmmm.2008.07.002

DO - 10.1016/j.mrfmmm.2008.07.002

M3 - Article

C2 - 18675828

AN - SCOPUS:49649083255

VL - 644

SP - 56

EP - 63

JO - Mutation Research

JF - Mutation Research

SN - 0027-5107

IS - 1-2

ER -