Genetically lowered microsomal epoxide hydrolase activity and tobacco-related cancer in 47,000 individuals

Julie Lee; Morten Dahl; Børge G Nordestgaard

doi:10.1158/1055-9965.epi-10-1165

Genetically lowered microsomal epoxide hydrolase activity and tobacco-related cancer in 47,000 individuals

Julie Lee, Morten Dahl, Børge G Nordestgaard

6 Citations (Scopus)

Abstract

Background: Two functional polymorphisms of the microsomal epoxide hydrolase (mEH) gene (EPHX1), Tyr113His (rs1051740) and His139Arg (rs2234922), have variably been found to influence susceptibility to various cancer forms. We tested whether genetically lowered mEH activity affects risk of developing cancer in the general population. Methods: We genotyped 47,089 individuals from the Danish general population for the Tyr113His and His139Arg polymorphisms in the EPHX1 gene and divided them into groups with predicted fast, intermediate, and slow mEH activity. Using Cox proportional hazards models, we calculated HRs for 26 individual cancer diagnoses and for groups of any cancer, tobacco-related cancers, estrogen-related female cancers, and other cancers. Results: Of the 47,089 individuals, 7,590 experienced a cancer event, and of these, 1,466 were tobacco-related. After multifactorial adjustment, the HRs (95% CI) for tobacco-related cancer were 1.1 (0.8-1.5) and 1.5 (1.1-2.0) in individuals with intermediate and slow mEH activity versus individuals with the fast phenotype (P _trend = 0.003). The corresponding HRs among ever-smokers were 1.1 (0.8-1.5) and 1.5 (1.1-2.0; P _trend = 0.003), whereas HRs among never-smokers did not differ from 1.0. Conclusions: Our results indicate that genetically lowered mEH activity is associated with increased risk of developing tobacco-related cancer among smokers in the general population; however, additional studies are needed to confirm our findings. Impact: To our knowledge, this is the largest study to investigate the association of mEH phenotype and genotype with tobacco-related cancers combined in the general population.

Original language	English
Journal	Cancer Epidemiology, Biomarkers & Prevention
Volume	20
Issue number	8
Pages (from-to)	1673-82
Number of pages	10
ISSN	1055-9965
DOIs	https://doi.org/10.1158/1055-9965.epi-10-1165
Publication status	Published - Aug 2011

Keywords

Aged
Cocarcinogenesis
Denmark
Epoxide Hydrolases
Female
Genetic Predisposition to Disease
Genotype
Humans
Male
Middle Aged
Neoplasms
Questionnaires
Smoking

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1158/1055-9965.epi-10-1165

Cite this

@article{96a2150a620f4a7ba481cd4e07097ba1,

title = "Genetically lowered microsomal epoxide hydrolase activity and tobacco-related cancer in 47,000 individuals",

abstract = "Background: Two functional polymorphisms of the microsomal epoxide hydrolase (mEH) gene (EPHX1), Tyr113His (rs1051740) and His139Arg (rs2234922), have variably been found to influence susceptibility to various cancer forms. We tested whether genetically lowered mEH activity affects risk of developing cancer in the general population. Methods: We genotyped 47,089 individuals from the Danish general population for the Tyr113His and His139Arg polymorphisms in the EPHX1 gene and divided them into groups with predicted fast, intermediate, and slow mEH activity. Using Cox proportional hazards models, we calculated HRs for 26 individual cancer diagnoses and for groups of any cancer, tobacco-related cancers, estrogen-related female cancers, and other cancers. Results: Of the 47,089 individuals, 7,590 experienced a cancer event, and of these, 1,466 were tobacco-related. After multifactorial adjustment, the HRs (95% CI) for tobacco-related cancer were 1.1 (0.8-1.5) and 1.5 (1.1-2.0) in individuals with intermediate and slow mEH activity versus individuals with the fast phenotype (P trend = 0.003). The corresponding HRs among ever-smokers were 1.1 (0.8-1.5) and 1.5 (1.1-2.0; P trend = 0.003), whereas HRs among never-smokers did not differ from 1.0. Conclusions: Our results indicate that genetically lowered mEH activity is associated with increased risk of developing tobacco-related cancer among smokers in the general population; however, additional studies are needed to confirm our findings. Impact: To our knowledge, this is the largest study to investigate the association of mEH phenotype and genotype with tobacco-related cancers combined in the general population.",

keywords = "Aged, Cocarcinogenesis, Denmark, Epoxide Hydrolases, Female, Genetic Predisposition to Disease, Genotype, Humans, Male, Middle Aged, Neoplasms, Questionnaires, Smoking",

author = "Julie Lee and Morten Dahl and Nordestgaard, {B{\o}rge G}",

note = "{\textcopyright}2011 AACR.",

year = "2011",

month = aug,

doi = "10.1158/1055-9965.epi-10-1165",

language = "English",

volume = "20",

pages = "1673--82",

journal = "Cancer Epidemiology, Biomarkers & Prevention",

issn = "1055-9965",

publisher = "American Association for Cancer Research (A A C R)",

number = "8",

}

TY - JOUR

T1 - Genetically lowered microsomal epoxide hydrolase activity and tobacco-related cancer in 47,000 individuals

AU - Lee, Julie

AU - Dahl, Morten

AU - Nordestgaard, Børge G

PY - 2011/8

Y1 - 2011/8

N2 - Background: Two functional polymorphisms of the microsomal epoxide hydrolase (mEH) gene (EPHX1), Tyr113His (rs1051740) and His139Arg (rs2234922), have variably been found to influence susceptibility to various cancer forms. We tested whether genetically lowered mEH activity affects risk of developing cancer in the general population. Methods: We genotyped 47,089 individuals from the Danish general population for the Tyr113His and His139Arg polymorphisms in the EPHX1 gene and divided them into groups with predicted fast, intermediate, and slow mEH activity. Using Cox proportional hazards models, we calculated HRs for 26 individual cancer diagnoses and for groups of any cancer, tobacco-related cancers, estrogen-related female cancers, and other cancers. Results: Of the 47,089 individuals, 7,590 experienced a cancer event, and of these, 1,466 were tobacco-related. After multifactorial adjustment, the HRs (95% CI) for tobacco-related cancer were 1.1 (0.8-1.5) and 1.5 (1.1-2.0) in individuals with intermediate and slow mEH activity versus individuals with the fast phenotype (P trend = 0.003). The corresponding HRs among ever-smokers were 1.1 (0.8-1.5) and 1.5 (1.1-2.0; P trend = 0.003), whereas HRs among never-smokers did not differ from 1.0. Conclusions: Our results indicate that genetically lowered mEH activity is associated with increased risk of developing tobacco-related cancer among smokers in the general population; however, additional studies are needed to confirm our findings. Impact: To our knowledge, this is the largest study to investigate the association of mEH phenotype and genotype with tobacco-related cancers combined in the general population.

AB - Background: Two functional polymorphisms of the microsomal epoxide hydrolase (mEH) gene (EPHX1), Tyr113His (rs1051740) and His139Arg (rs2234922), have variably been found to influence susceptibility to various cancer forms. We tested whether genetically lowered mEH activity affects risk of developing cancer in the general population. Methods: We genotyped 47,089 individuals from the Danish general population for the Tyr113His and His139Arg polymorphisms in the EPHX1 gene and divided them into groups with predicted fast, intermediate, and slow mEH activity. Using Cox proportional hazards models, we calculated HRs for 26 individual cancer diagnoses and for groups of any cancer, tobacco-related cancers, estrogen-related female cancers, and other cancers. Results: Of the 47,089 individuals, 7,590 experienced a cancer event, and of these, 1,466 were tobacco-related. After multifactorial adjustment, the HRs (95% CI) for tobacco-related cancer were 1.1 (0.8-1.5) and 1.5 (1.1-2.0) in individuals with intermediate and slow mEH activity versus individuals with the fast phenotype (P trend = 0.003). The corresponding HRs among ever-smokers were 1.1 (0.8-1.5) and 1.5 (1.1-2.0; P trend = 0.003), whereas HRs among never-smokers did not differ from 1.0. Conclusions: Our results indicate that genetically lowered mEH activity is associated with increased risk of developing tobacco-related cancer among smokers in the general population; however, additional studies are needed to confirm our findings. Impact: To our knowledge, this is the largest study to investigate the association of mEH phenotype and genotype with tobacco-related cancers combined in the general population.

KW - Aged

KW - Cocarcinogenesis

KW - Denmark

KW - Epoxide Hydrolases

KW - Female

KW - Genetic Predisposition to Disease

KW - Genotype

KW - Humans

KW - Male

KW - Middle Aged

KW - Neoplasms

KW - Questionnaires

KW - Smoking

U2 - 10.1158/1055-9965.epi-10-1165

DO - 10.1158/1055-9965.epi-10-1165

M3 - Journal article

C2 - 21653646

SN - 1055-9965

VL - 20

SP - 1673

EP - 1682

JO - Cancer Epidemiology, Biomarkers & Prevention

JF - Cancer Epidemiology, Biomarkers & Prevention

IS - 8

ER -

Genetically lowered microsomal epoxide hydrolase activity and tobacco-related cancer in 47,000 individuals

Abstract

Keywords

UN SDGs

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