***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Cigarette smoking is a risk factor for  colorectal adenoma , a precursor of colorectal cancer . Microsomal epoxide hydrolase ( EPHX1 ) metabolizes polycyclic aromatic hydrocarbons , carcinogens found in cigarette smoke . Nonsynonymous variants of EPHX1 at Tyr(113)His ( exon 3 ) and His(139)Arg ( exon 4 ) are associated , respectively , with low ( (113)His ) and high ( (139)Arg ) predicted activity . Among participants r and omized to the screening arm of the Prostate , Lung , Colorectal , and Ovarian Cancer Screening Trial , we evaluated risks for advanced adenoma in relation to cigarette use and these two EPHX1 variants . We compared 772 cases with advanced adenoma ( adenoma > /=1 cm or containing high- grade dysplasia or villous , including tubulovillous , elements ) of the distal colon ( left-sided , descending colon and sigmoid or rectum ) to 777 gender- and age-matched controls who were screen-negative for left-sided adenoma . Compared to those with homozygous genotypes predicting low EPHX1 activity , advanced adenoma risks tended to be elevated for carriers of (113)TyrTyr [ odds ratios ( OR ) , 1.5 ; 95 % confidence intervals ( CI ) , 1.0 - 2.2 ] and (139)ArgArg ( OR , 1.4 ; 95 % CI , 0.8 - 2.5 ) and for subjects who carried a greater number of the alleles ( (113)Tyr or (139)Arg ) associated with high predicted enzymatic activity ( P(trend ) = 0.03 ) . The increased risk associated with the increasing number of putative high-activity alleles was most apparent among current and recent ( quit < 10 years ) cigarette smokers ( P(trend ) = 0.02 ) . In conclusion , EPHX1 variants at codon 113 and 139 associated with high predicted enzymatic activity appear to increase risk for colorectal adenoma , particularly among recent and current smokers Microsomal epoxide hydrolase ( mEH ) is involved in the metabolism of environmental and tobacco carcinogens . Smaller studies found inconsistent results in the relationship between mEH polymorphisms and lung cancer risk . We investigated the two polymorphisms of mEH in 974 Caucasian lung cancer patients and 1142 controls using PCR-RFLP techniques .  The results were analyzed using generalized additive models and logistic regression , adjusting for relevant covariates . There was no overall relationship between mEH genotypes and lung cancer risk . The adjusted odds ratio ( OR ) of the very low activity genotype versus that of other genotypes combined was 1.00 [ 95 % confidence interval ( CI ) , 0.74 - 1.34 ] . However , gene-environment interaction analyses revealed that the ORs decreased as cumulative smoking ( defined as square root of pack-years ) increased . When pack-years = 0 , the OR was 1.89 ( 95 % CI , 1.08 - 3.28 ) . When pack-years = 28.5 , the OR was 1.00 ( 95 % CI , 0.76 - 1.32 ) , and when pack-years = 80 , the OR decreased to 0.65 ( 95 % CI , 0.42 - 1.00 ) . When cases were stratified according to histological subtypes , the interaction between mEH genotype and cumulative smoking was statistically significant ( P < 0.01 ) for the 222 squamous cell carcinoma cases , whereas it was not significant ( P = 0.18 ) for the 432 adenocarcinoma cases . In conclusion , cumulative cigarette smoking plays a pivotal role in the association between mEH polymorphisms and lung cancer risk , altering the direction of risk ( in the case of the very low activity genotype ) from a risk factor in nonsmokers to a relatively protective factor in heavy smokers 
    Output:
    
/ SIGNIFICANCE Putative low EPHX1 enzyme activity may have a potential protective effect on tobacco-related carcinogenesis of lung and UADT cancers , whereas putative high EPHX1 activity may have a harmful effect .
Moreover , cigarette-smoking status may influence the association of EPHX1 enzyme activity and the related cancer risk