***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 use is a risk factor for colorectal adenoma , a known precursor of colorectal cancer . Polymorphic variants in NQO1 and CYP1A1 influence the activation of carcinogenic substances in tobacco smoke , possibly impacting on tobacco-associated risks for colorectal tumors . We investigated the association of cigarette smoking with risk for advanced colorectal adenoma in relation to the CYP1A1 Val(462 ) and NQO1 Ser(187 ) polymorphic variants . Subjects were 725 non-Hispanic Caucasian cases with advanced colorectal adenoma of the distal colon ( descending colon , sigmoid and rectum ) and 729 gender- and ethnicity-matched controls , r and omly selected from participants in the prostate , lung , colorectal and ovarian cancer screening trial . Subjects carrying either CYP1A1 Val(462 ) or NQO1 Ser(187 ) alleles were weakly associated with risk of colorectal adenoma ; however , subjects carrying both CYP1A1 Val(462 ) and NQO1 Ser(187 ) alleles showed increased risks ( OR = 2.2 , 95 % CI = 1.1 - 4.5 ) , particularly among recent ( including current ) ( OR = 17.4 , 95 % CI = 3.8 - 79.8 , P for interaction = 0.02 ) and heavy cigarette smokers ( > 20 cigarettes/day ) ( OR = 21.1 , 95 % CI = 3.9 - 114.4 , P for interaction = 0.03 ) compared with non-smokers who did not carry either of these variants . These genotypes were unassociated with risk in non-smokers . In analysis of adenoma subtypes , the combined gene variants were most strongly associated with the presence of multiple adenoma ( P = 0.002 ) . In summary , joint carriage of CYP1A1 Val(462 ) and NQO1 Ser(187 ) alleles , particularly in smokers , was related to colorectal adenoma risk , with a propensity for formation of multiple lesions Polymorphisms in CYP1A1 and CYP1B1 genes in humans are associated with reduction of enzymatic activity towards several substrates , including those found in tobacco smoke . To investigate the potential role these polymorphisms have as modulators of early-onset lung cancer risk , a population -based case-control study involving early-onset lung cancer cases was performed . Biological sample s were available for 383 individuals diagnosed prior to 50 years of age identified from the metropolitan Detroit Surveillance , Epidemiology and End Results ( SEER ) program and 449 age , race and sex-matched controls ascertained through r and om digit dialing .  Genotype frequencies varied significantly by race for CYP1A1 Ile(462)Val and CYP1B1 Leu(432)Val genotypes , so all analyses were stratified by race . No association was seen between lung cancer risk and polymorphisms in CYP1A1 Msp1 or CYP1B1 Leu(432)Val for Caucasians or African Americans , after adjusting for age at diagnosis , sex , pack years of smoking and family history of lung cancer . In Caucasians , those with the IIe/Val genotype at CYP1A1 Ile(462)Val locus were at decreased risk of having lung cancer compared to those with the lle/lle genotype , after adjusting for age at diagnosis , sex , pack years of smoking and family history of cancer ( OR=0.41 95 % Cl 0.19 - 0.90 ) . These results were not replicated among the African American population , nor were they modified by amount of smoking Cigarette smoking is a risk factor for colon adenoma . The glutathione S-transferase enzymes are involved in the detoxification of carcinogenic compounds including those found in tobacco smoke , and thus , may be important modifiers of individual risk of developing this disease . We examined the prevalence of GSTM1 and GSTT1 gene deletions , and two GSTP1 polymorphisms in 772 cases with advanced colorectal adenomas ( > 1 cm , villous elements or high- grade dysplasia ) of the distal colon ( descending or sigmoid colon or rectum ) and 777 sigmoidoscopy negative controls enrolled in the screening arm of the Prostate , Lung , Colorectal , and Ovarian Cancer Screening Trial . Epidemiologic data on smoking was collected by self-administered question naire and DNA was extracted from whole blood or buffy coat . For GSTM1 and GSTT1 , we used a newly developed TaqMan-based assay capable of discriminating heterozygous ( + /− ) individuals from those with two active alleles ( + /+ ) and homozygous deletions ( −/− ) . For GSTP1 , the I105V and the A114V substitutions were identified using end point 5′ nuclease assays ( TaqMan ) . Adjusted odds ratios ( OR ) and 95 % confidence intervals ( 95 % CI ) were determined using unconditional logistic regression , controlling for age , race , and gender . Advanced adenoma risk was increased in current/former smokers ( OR , 1.4 ; 95 % CI , 1.2 - 1.8 ) . Risks were decreased in subjects with ≥1 inactive GSTM1 alleles ( OR , 0.6 ; 95 % CI , 0.4 - 0.9 ) ; and the association was independent of smoking status ( P interaction = 0.59 ) . Having ≥1 inactive GSTT1 allele was associated with increased risk among smokers ( OR , 1.4 ; 95 % CI , 1.1 - 1.9 ; Ptrend = 0.02 ) but not among never smokers ( OR , 0.9 ; 95 % CI , 0.6 - 1.3 ) and a significant interaction between smoking and genotype was observed ( P interaction = 0.05 ) . In summary , this is the first study to report associations between colorectal adenomas and GSTM1 wild-type and GSTT1 null allele among smokers . These findings only became apparent using a newly developed assay able to distinguish heterozygous from wild-type individuals . Our data provide evidence that phenotypic differences between these two groups exist Purpose Here we assessed associations between null mutations in glutathione-S-transferase (GST)T1 and GSTM1 genes , and the rs1695 polymorphism in GSTP1 ( Ile105Val ) , and risk of breast cancer-specific ( n=45 ) and all-cause ( n=99 ) mortality in a multiethnic , prospect i ve cohort of 533 women diagnosed with stage I-IIIA breast cancer in 1995–1999 , enrolled in the Health , Eating , Activity , and Lifestyle ( HEAL ) Study . Methods We measured the presence of the null mutation in GSTT1 and GSTM1 , and the rs1695 polymorphism in GSTP1 by polymerase chain reaction . We assessed associations between breast-cancer specific and all-cause mortality using Cox proportional hazards models . Results Participants with ER-negative tumors were more likely to be GSTT1 null ( χ2=4.52 ; P=0.03 ) , and African American women were more likely to be GSTM1 null ( χ2=34.36 ; P<0.0001 ) . Neither GSTM1 nor GSTT1 null mutations were associated with breast cancer-specific or all-cause mortality . In a model adjusted for body mass index , race/ethnicity , tumor stage and treatment received at diagnosis , the variant Val allele of rs1695 was associated with increased risk of all-cause ( HR=1.81 , 95 % CI 1.16 - 2.82 , P=0.008 ) , but not breast cancer-specific mortality . The GSTT1 null mutation was associated with significantly higher levels of C-reactive protein . Conclusions GSTM1 and GSTT1 null genotypes had no effect on outcome ; however the variant allele of rs1695 appears to confer increased risk for all-cause mortality in breast-cancer survivors . Given the limited sample size of most studies examining associations between GST polymorphisms with breast cancer survival , and the lack of women undergoing more contemporary treatment protocol s ( treated prior to 1999 ) , it may be helpful to re-examine this issue among larger sample s of women diagnosed after the late 1990s , who all received some form of chemotherapy or radiotherapy Background Tumor-related methylated DNA and circulating tumor cells ( CTC ) in the peripheral blood might be of prognostic importance in breast cancer . Thus , the aim of our study was to examine free methylated DNA and CTC in the blood from breast cancer patients and to correlate it with clinicopathological features known to influence prognosis . Material s and methods We prospect ively obtained serum sample s from 85 patients with breast cancer and 22 healthy volunteers . Sera were analysed by methylation specific PCR ( MethyLight PCR ) for five genes : adenomatous polyposis coli ( APC ) , ras association domain family protein 1A ( RASSF1A ) , estrogen receptor 1 ( ESR1 ) , CDKN2A ( p16 ) and glutathione s-transferase pi 1 ( GSTP1 ) . Beta actin ( ACTB ) served as control . In parallel matched peripheral blood of 63 patients was used to assay for circulating tumor cells in the peripheral blood by a modified immunomagnetic AdnaTest BreastCancerSelect with PCR detection for EPCAM , MUC1 , MGB1 and SPDEF . Results We found a hypermethylation in the APC gene in 29 % ( 25/85 ) , in RASSF1A in 26 % ( 22/85 ) , in GSTP1 in 18 % ( 14/76 ) and in ESR1 in 38 % ( 32/85 ) of all breast cancer patients . No hypermethylation of CDKN2A was found ( 0/25 ) . Blood sample s of patients were defined CTC positive by detecting the EPCAM 13 % ( 8/63 ) , MUC1 16 % ( 10/63 ) , MGB 9 % ( 5/55 ) , SPDEF 12 % ( 7/58 ) and in 27 % detecting one or more genes ( 15/55 ) . A significant difference was seen in methylated APC DNA between cancer patients and healthy volunteers . Moreover , methylated APC , RASSF1 and CTC were significantly different in metastatic versus non-metastatic disease . In addition , the presence of methylated APC , RASSF1A and CTC correlated significantly with AJCC-staging ( p = 0.001 , p = 0.031 and 0.002 , respectively ) . High incidences of methylations were found for the genes RASSF1 and ESR1 in healthy individuals ( both 23 % 5/22 ) . Methylated GSTP1 was predominantly found in the serum of patients with large primaries ( p = 0.023 ) and was highly significantly correlated with positive Her2/neu status ( p = 0.003 ) . Elevated serum CA15.3 was strongly correlated with methylated APC and CTC detection ( both p = 0.000 ) . Methylated ESR1 failed to exhibit significant correlations with any of the above mentioned parameters . The presence of CTC in peripheral blood was significantly associated with methylated APC ( p = 0.012 ) and methylated GSTP1 ( p = 0.001 ) . Conclusion The detection of methylated APC and GSTP1 DNA in serum correlated with the presence of CTC in the blood of breast cancer patients . Both methylated DNA and CTC correlated with a more aggressive tumor biology and advanced disease A protective role of glucosinolates in prostate cancer development might be mediated by the induction of biotransformation enzymes . These enzymes , enhancing the elimination of carcinogens from the body , are known to be polymorphic . Therefore , we evaluated whether a possible association between glucosinolate intake and prostate cancer risk is modified by polymorphisms in GSTT1 , GSTM1 , GSTA1 , GSTP1 , or NOQ1 genes . A case-control study including 248 prostate cancer cases and 492 matched controls was nested in the prospect i ve European Prospect i ve Investigation into Cancer and Nutrition-Heidelberg cohort . At baseline , participants provided dietary and lifestyle data and blood sample s , which were used for genotyping and measurement of serum glutathione S-transferase-α concentration .  Odds ratios and 95 % confidence intervals were calculated by conditional logistic regression . We found an inverse association of glucosinolate intake with prostate cancer risk ( adjusted odds ratio , 0.72 per 10 mg/d increment ; 95 % confidence interval , 0.53 - 0.96 ) . Stratification by genotype showed significantly reduced risks for subjects with wild-type of NQO1 ( C609 T ) compared with CT or TT carriers ( Pinteraction = 0.04 ) . Those with deletions in both GSTM1 and GSTT1 genes combined had a significantly reduced risk with increasing glucosinolate intake ( Pinteraction = 0.01 ) . There was no effect modification of glucosinolate intake and cancer risk by GSTA1 ( G-52A ) or GSTP1 ( A313 G 
    Output:
    
Our finding , based on systematic review and experimental data suggest that the polymorphic CYP1A1 and GSTP1 genes may contribute to risk of developing breast cancer