|Year : 2016 | Volume
| Issue : 4 | Page : 524-528
Evaluation of deletion polymorphisms of glutathione S-transferase genes and colorectal cancer risk in ethnic Kashmiri population: A case–control study
S Nissar1, AS Sameer2, R Rasool3, NA Chowdri4, F Rashid5
1 Department of Biochemistry, University of Kashmir; Department of Immunology and Molecular Medicine, Sher-I-Kashmir Institute of Medical Sciences; Department of Clinical Biochemistry, University of Kashmir, Srinagar, Jammu and Kashmir, India
2 Department of Basic Medical Sciences, College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Jeddah, KSA
3 Department of Immunology and Molecular Medicine, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India
4 Department of Surgery, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India
5 Department of Clinical Biochemistry, University of Kashmir, Srinagar, Jammu and Kashmir, India
|Date of Web Publication||21-Apr-2017|
Department of Clinical Biochemistry, University of Kashmir, Srinagar, Jammu and Kashmir
Source of Support: None, Conflict of Interest: None
AIM: Glutathione S.transferases. (GSTs) are known to play a pivotal role in the detoxification of potential carcinogens, and their gene variation may alter susceptibility to colorectal cancer. (CRC). The aim of the study was to evaluate the genetic association of GSTM1 and GSTT1 gene deletion/null polymorphism with disease susceptibility and risk development in CRC patients of ethnic Kashmiri population. MATERIALS AND METHODS: Genotype frequencies of GSTM1 and GSTT1 gene deletion/null polymorphism were compared between 160 CRC patients and 200 healthy controls using polymerase chain reaction multiplex. RESULTS: The frequency of GSTM1-null was found to be 76.2% in cases and 81.5% in controls and odds ratio. (OR) = 1.37 (95% confidence interval. [CI]: 0.82–2.28). Likewise, the GSTT1-null genotype was found in 75.5% of cases and 77.5% of controls and the OR = 1.14 (95% CI: 0.76–1.8). The overall association between the GSTM1-null and GSTT1-null polymorphism and the CRC cases was found to be insignificant (P < 0.05). However, individuals with double-null genotype (GSTM1-/GSTT1-) were found to have 3.5-fold increased risk for the development of CRC. Further, the risk genotype (null) of GSTT1 was found to be associated with tumor grade (P = 0.001) and GSTM1 (null) genotype was significantly associated with smoking status (P = 0.004), when compared to the (present) genotype in CRC cases. CONCLUSION: Our results suggest that GSTM1 and GSTT1 gene deletion/null gene polymorphisms are not a key modulators of the risk of developing CRC in Kashmiri population.
Keywords: Colorectal cancer, GSTM1, GSTT1, Kashmir, polymerase chain reaction multiplex, polymorphism
|How to cite this article:|
Nissar S, Sameer A, Rasool R, Chowdri N, Rashid F. Evaluation of deletion polymorphisms of glutathione S-transferase genes and colorectal cancer risk in ethnic Kashmiri population: A case–control study. Indian J Cancer 2016;53:524-8
|How to cite this URL:|
Nissar S, Sameer A, Rasool R, Chowdri N, Rashid F. Evaluation of deletion polymorphisms of glutathione S-transferase genes and colorectal cancer risk in ethnic Kashmiri population: A case–control study. Indian J Cancer [serial online] 2016 [cited 2019 Dec 7];53:524-8. Available from: http://www.indianjcancer.com/text.asp?2016/53/4/524/204754
| » Introduction|| |
Colorectal cancer (CRC) represents the third most common malignancy worldwide and the second leading cause of cancer-related death in many parts of the Western world. It is the third most common cancer in men and the second most common cancer in women worldwide. In Kashmir valley, CRC has been reported to be the third most common gastrointestinal cancer ,,, after esophageal and gastric cancer.
Glutathione S-transferases (GSTs) are the important multigenic family of Phase II drug-metabolizing enzymes which catalyze the conjugation of an electrophilic species of a large variety of endogenous and exogenous compounds, including carcinogens and xenobiotic as well as their metabolites with reduced glutathione leading to the elimination of toxic compounds.
Human GSTs are divided into three main families: Cytosolic, mitochondrial, and membrane-bound microsomal. The cytosolic and mitochondrial GSTs are soluble enzymes with three-dimensional fold structural similarity, whereas microsomal GSTs designated as “membrane-associated proteins in eicosanoid and glutathione metabolism” are structurally distinct from cytosolic GSTs but are functionally similar in the ability to catalyze the conjugation of glutathione to electrophilic compounds. There are at least seven distinct classes of cytosolic GSTs, namely, alpha (A), mu (M), pi (P), sigma (S), zeta (Z), omega (O), and theta (T), based on differences in amino acid sequence, and each gene is mapped on different chromosomes.,
GSTM1 is one of the genes encoded by a 100kb gene cluster located on chromosome 1p13.3, encoding the mu class of enzymes and has three polymorphisms. One polymorphism is a deletion that results in a lack of functional gene product (GSTM1-null). The other two, GSTM1*A and GSTM1*B, differ by a C519G substitution, resulting in asparagine to lysine substitution at amino acid 173.
GSTT class consists of two genes, GSTT1 and GSTT2, located at 22q11.2 and separated by about 50-kb. Similar to GSTM1, the most common genetic variant in GSTT1 consists of a deletion of the whole gene, resulting in the lack of active enzyme. Another less common polymorphism (rs11550605) results in a threonine to proline substitution at amino acid 104.
GST gene polymorphisms are mostly associated with a lack or an alteration of enzymatic activity toward several substrates,,, thus with increased CRC susceptibility.,,, In the case of GSTT1-null, which occurs at frequencies of 11%–38% in different populations, 50 kb of genomic sequence containing the entire gene is deleted. While for the GSTM1- null, variable frequencies have a range of 20%–70%, involving a 15kb sequence deletion.,,
In the present case–control study, we determined the genotypic frequency of the GSTM1-null and GSTT1-null polymorphism in CRC patients to substantiate its association with CRC risk in the sample of Kashmiri population.
| » Materials and Methods|| |
This study included 160 consecutive primary CRC patients. All CRC patients were recruited from the Department of Surgery, Sher-I-Kashmir Institute of Medical Science. Tumor types and stages were determined by two experienced pathologists. Blood samples of 200 age- and sex-matched cases with no signs of any malignancy were collected for controls. The mean age of both patient and control groups was 55 years.
Data on all CRC patients were obtained from personal interviews with patients and/or guardians, medical records, and pathology reports. The data collected included sex, age, dwelling, tumor location, Dukes stage, and lymph node status. All patients and/or guardians were informed about the study and their will to participate in this study was taken on predesigned questionnaire (available on request). The collection and use of tumor and blood samples for this study were previously approved by the appropriate Institutional Ethics Committee.
DNA extraction and genotype analysis
DNA extraction was performed using ammonium acetate method. The extraction product was stored at −20°C. 2.5 μL of DNA was used as the template for each polymerase chain reaction (PCR). Genotype analysis of GSTM1 and GSTT1 gene was performed by the PCR multiplex using previously described primers. Primers: GSTM1 _R 50-GTT GGGCTCAAATATACGGTGG-30; GSTM1 _F 5'-GAACTCCCTGAAAAGCTAAAGC-3' and GSTT1_R 5'-TCACCGGATCATGGCCAGCA-3'; GSTT1_F 5'-TTCCTCACTGGTCCTCACATCTC-3'. The GSTM1 fragment was 215 bp, and the GSTT1 fragment was 480 bp. Each set of reaction included both positive and negative controls. The multiplex PCR method was used to detect the presence or absence of the GSTT1 and GSTM1 genes in the genomic DNA samples, simultaneously in the same tube. Briefly, PCR was carried out in a final volume of 25 μL containing 50 ng genomic DNA template, 1X PCR buffer with 2 mM MgCl2, 0.5 μM of each primer, 50 μM dNTPs, and 0.5 U DNA polymerase. For PCR amplification, the standard program was used as follows: One initial denaturation steps at 94°C for 7 min, followed by 35 denaturation cycles of 1 min at 94°C, 1 min of annealing at 58°C, and 1 min of extension at 72°C, followed by a final elongation cycle at 72°C for 10 min. The PCR products were electrophoresed in 2% agarose gels and visualized by ethidium bromide staining. DNA from samples positive for GSTM1 and GSTT1 genotypes yielded bands of 215 and 480 bp, respectively.
The quality control included the assessment of genotyping errors including the false estimates of a particular allele frequency and the evaluation of the reproducibility of the genotyping done. For these assessments, approximately 10% of the patient and control samples selected randomly were re-genotyped. In addition, in each PCR-restriction fragment length polymorphism setup, previously amplified and genotyped samples representing different genotypic scenarios were included as a reference control.
The observed frequencies of the above genotypes in patients with CRC were compared with the control using Chi-square or Fisher's exact test when the expected frequencies were small. The Chi-square test was used to verify whether the genotype distributions were in Hardy–Weinberg equilibrium. Statistical significance was set at P< 0.05. Statistical analyses were performed using SPSS version 22 software (Armonk, NY).
The effective sample size and the statistical power were computed using the “Genetic Power Calculator” developed by Purcell et al. (2003) (http://pngu.mgh.harvard.edu/~purcell/gpc/). The statistical power of 80% is widely used in genetic association studies to avoid Type II errors and to determine a cost-effective sample size under the assumption of 10%–25% variant allele frequency, 1:1 case–control ratio, and 5% Type I error rate (α). We obtained a healthy power score of about 85% for the single nucleotide polymorphism under the study in our case–control study design, with 160 case subjects and 200 control subjects.
| » Results|| |
A total of 160 cases and 200 control subjects were included in this study with prior consent. All of the cases presented constipation and bleeding per rectum as their chief complaint. Furthermore, out of 160 confirmed cases of CRC, 96 cases were male and 64 cases were female, 88 were rural and 72 were urban, 70 had carcinoma in colon and 90 in rectum, and 73 were smokers and 87 nonsmokers [Table 1]. The mean age of patients having confirmed CRC was 55 years. Among controls, 102 were male and 98 were female. No significant gender- or age-related differences were observed between the study groups (P > 0.05).
|Table 1: Frequency distribution analysis of selected demographic and risk factors in colorectal cancer cases and controls|
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Among the 360 subjects (160 cases and 200 controls), the frequency of GSTM1- null was found to be 76.2% in cases and 81.5% in controls and odds ratio (OR) = 1.37 (95% confidence interval [CI]: 0.82–2.28). Likewise, the GSTT1-null genotype was found in 75.5% of cases and 77.5% of controls and OR = 1.14 (95% CI: 0.76–1.8) [Table 2]. The overall association between the GSTM1- and GSTT1-null polymorphism and the CRC cases was found to be insignificant (P < 0.05). GSTM1- and GSTT1-null genotypes were similar for cases and controls.
|Table 2: Genotype frequencies of GSTM1 and GSTT1 gene polymorphism in colorectal cancer cases and controls|
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The distribution analysis for the both GSTT1 and GSTM1 genotypes showed a low frequency of individuals for both case and control groups (5% and 1.5%, respectively) who had a double-null genotype (GSTM1−/GSTT1−) and a higher prevalence of individuals with a double present genotype (GSTM1+/GSTT1+) for both groups (56.2% and 60.5%, respectively). Furthermore, there was no significant difference in any of the genotype combinations. However, individuals with double-null genotype (GSTM1−/GSTT1−) were found to have increased risk for development of CRC (OR = 3.5, 95% CI: 0.9–13.8) [Table 3].
|Table 3: Distribution frequencies of genotype combination between GSTM1 and GSTT1 gene polymorphism in colorectal cancer cases and controls and risk analysis|
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Despite the fact that GST deletion polymorphisms did not have any CRC susceptibility, the influence of GSTT1 and GSTM1 deletion on clinicopathological variables was analyzed in the group of patients that were studied by comparing individuals with null and present genotypes. It was found that the risk genotype (null) of GSTT1 is associated with tumor grade (P = 0.001) and GSTM1 (null) genotype was significantly associated with smoking status (P = 0.004), when compared to the (present) genotype in CRC cases [Table 4] and [Table 5].
|Table 4: Association of GSTM1 genotypes with various clinicopathological variables in colorectal cancer patients|
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|Table 5: Association of GSTT1 genotypes with various clincopathological variables in colorectal cancer patients|
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| » Discussion|| |
The present hospital-based case–control study was conducted to investigate the possible role of GSTM1 and GSTT1 gene deletion/null polymorphisms and their relation with the risk of CRC in ethnic Kashmiri population.
Xenobiotic-metabolizing enzymes, GSTs constitute an important line of defense against a variety of carcinogens. The genetic variants thus can be more or less efficient in metabolizing carcinogen, thereby contributing to individual disease susceptibility depending on the substrate metabolized. Several studies have shown influence of GSTs polymorphism in cancer susceptibility due to their role in modulation of the biological effects of the carcinogens. Furthermore, the relation between genetic polymorphisms of GSTs and cancer risk has been studied thoroughly, demonstrating either positive or negative relation between the GST polymorphisms and CRC.
GST gene polymorphism may exert an effect on the functioning of GST enzymes through the change in both the level of gene expression and activity of the protein itself. In this way, it has an influence on the possibility of detoxification of carcinogens, and consequently, the level of DNA damage; thus, it may have an indirect effect on the risk of development of cancer.
For GSTM1-null genotype, the frequencies are higher in Caucasians (34%–58.3%), Asians (47.6%–56.2%), and Arabs (44%–56.3%) than in Africans (17%–46.7%) and in native Latin-American populations (0%–43%). GSTT1-null genotype is lower in Caucasians, South American natives (0%–38.2%) and increases significantly in Asian populations (64.4%) and similar frequencies among Arabian and African descendants.
A meta-analysis by Economopoulos and Sergentanis  observed that GSTM1-null allele carriers exhibited increased CRC risk in Caucasian populations (pooled OR = 1.150, 95% CI: 1.060–1.248, and random effects), whereas no significant association was detected for Chinese subjects (pooled OR = 1.025, 95% CI: 0.903–1.163, and fixed effects). Similarly, GSTT1-null allele carriers exhibited increased CRC risk in Caucasian populations (pooled OR = 1.312, 95% CI: 1.119–1.538, and random effects) whereas no significant association in Chinese subjects was observed (pooled OR = 1.068, 95% CI: 0.788–1.449, and random effects). GSTM1- and GSTT1-null genotypes confer additional risk for CRC in Caucasian populations.
Wang et al., 2011 conducted a study which confirmed that the GSTM1-null genotype is significantly related to an increased risk of rectal cancer and the GSTT1-null genotype to an increased risk of colon cancer. In addition, it was suggested that the concomitance of polymorphism in three genes, GSTM1, GSTT1, and GSTP1, may be an important factor predisposing to the development of CRC in the Hindu population.
In our study, we found the frequency of GSTM1- null to be 76.2% in cases and 81.5% in controls and GSTT1-null genotype to be 75.5% in cases and 77.5% in controls. The overall association between the GSTM1- null and GSTT1-null polymorphism and the CRC cases was found to be insignificant (P < 0.05). Further individuals with double-null genotype (GSTM1−/GSTT1−) were found to have 3.5-fold increased risk for development of CRC.
We did not find any association between GSTM1 polymorphism and CRC risk. Despite some divergence in the literature data, our findings are in accordance with many other studies ,,, which also revealed no association. On the contrary, Sachse et al. found a significant association between GSTM1-null genotype carriers and an increased CRC risk. Similarly, Cotterchio et al. confirmed that GSTT1 gene polymorphism significantly modified the relationship between the consumption of red meat and CRC risk, while GSTM1 gene polymorphism did not change this risk. The association between GSTM1-null genotype carriers and a reduced risk of CRC may be related to their role of in the disposition of isothiocyanates, breakdown products of glucosinolates, which are abundant in cruciferous vegetables, and strong inducers of the GSTs and other detoxification enzymes. The GSTM1-null polymorphism, associated with reduced enzyme activity, may result in longer circulating half-lives of inverse transition cycling and potentially greater chemopreventive effects of cruciferous vegetables, thereby contradicting the primary hypothesis whereby the GSTM1-null genotypes are eventually at higher cancer risk due to lower capacity carcinogen disposition.
We found no significant association between the GSTT1-null genotype and CRC risk. The lack of association is in agreement with the results found in many other studies.,, However, the meta-analysis by de Jong et al., 2002 and Butler et al., 2001 are reported the opposite findings. Furthermore, the relation between genetic polymorphisms in GSTs and cancer risk has been studied vividly, demonstrating either positive or negative relation between the GST polymorphisms and CRC.
The deviation in results from different studies may be related to the fact that environmental or genetic factors are of fundamental importance in disease risk and may be influenced by ethnic diversity. Further, it is supposed that some populations could be more susceptible to chemical-induced carcinogenesis than others and influence of genetic determinants of cancer may be modulated by other modifying genes, specific environmental factors, other diseases as well as lifestyle which demonstrate a powerful or strong effect.
| » Conclusion|| |
Our study did not find any association between GSTM1 and GSTT1 gene polymorphisms and CRC risk, thereby suggesting that these polymorphisms do not confer any additional risk for CRC in Kashmiri population.
The authors wish to thank each and every CRC patient who took part in this study and cooperated during the interview and sample collection. The authors also thank Prof. Zafar Amin Shah, Head Department of Immunology and Molecular Medicine, SKIMS, Soura for his professional help and support in carrying out this study. We also thank the head and technical staff of the operating theatre in the Department of General Surgery, Sher-I-Kashmir Institute of Medical Sciences, Kashmir who helped us with tissue procurement, and the anonymous pathologists at the Department of Pathology, Sher-I-Kashmir Institute of Medical Sciences, Kashmir for the histopathological assessment of the tumour tissues.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| » References|| |
Gellad ZF, Provenzale D. Colorectal cancer: National and international perspective on the burden of disease and public health impact. Gastroenterology 2010;138:2177-90.
Torre LA, Siegel RL, Ward EM, Jemal A. Global cancer incidence and mortality rates and trends—an update. Cancer Epidemiol. Biomark Prev 2016;25:16-27.
Rasool MT, Lone MM, Wani ML, Afroz F, Zaffar S, Mohib-ul Haq M. Cancer in Kashmir, India: Burden and pattern of disease. J Cancer Res Ther 2012;8:243-6.
Sameer AS, Nissar S, Abdullah S, Chowdri NA, Siddiqi MA. DNA repair gene 8-oxoguanine DNA glycosylase Ser326Cys polymorphism and colorectal cancer risk in a Kashmiri population. DNA Cell Biol 2012;31:541-6.
Sameer AS. Colorectal cancer: A researcher's perspective of the molecular angel's gone eccentric in the Vale of Kashmir. Tumour Biol 2013;34:1301-15.
Sameer AS. Colorectal cancer: Molecular mutations and polymorphisms. Front Oncol 2013;3:114.
Hayes JD, Flanagan JU, Jowsey IR. Glutathione transferases. Annu Rev Pharmacol Toxicol 2005;45:51-88.
Hayes JD, Strange RC. Glutathione S-transferase polymorphisms and their biological consequences. Pharmacology 2000;61:154-66.
Xu S, Wang Y, Roe B, Pearson WR. Characterization of the human class Mu glutathione S-transferase gene cluster and the GSTM1
deletion. J Biol Chem 1998;273:3517-27.
Rebbeck TR. Molecular epidemiology of the human glutathione S-transferase genotypes GSTM1
and GSTT1 in cancer susceptibility. Cancer Epidemiol Biomark Prev 1997;6:733-43.
Landi S. Mammalian class theta GST and differential susceptibility to carcinogens: A review. Mutat Res 2000;463:247-83.
Sprenger R, Schlagenhaufer R, Kerb R, Bruhn C, Brockmöller J, Roots I, et al.
Characterization of the glutathione S-transferase GSTT1 deletion: Discrimination of all genotypes by polymerase chain reaction indicates a trimodular genotype-phenotype correlation. Pharmacogenetics 2000;10:557-65.
Alexandrie AK, Rannug A, Juronen E, Tasa G, Warholm M. Detection and characterization of a novel functional polymorphism in the GSTT1 gene. Pharmacogenetics 2002;12:613-9.
Whyatt RM, Perera FP, Jedrychowski W, Santella RM, Garte S, Bell DA. Association between polycyclic aromatic hydrocarbon-DNA adduct levels in maternal and newborn white blood cells and glutathione S-transferase P1 and CYP1A1 polymorphisms. Cancer Epidemiol Biomarkers Prev 2000;9:207-12.
McIlwain CC, Townsend DM, Tew KD. Glutathione S-transferase polymorphisms: Cancer incidence and therapy. Oncogene 2006;25:1639-48.
Sachse C, Smith G, Wilkie MJ, Barrett JH, Waxman R, Sullivan F, et al.
A pharmacogenetic study to investigate the role of dietary carcinogens in the etiology of colorectal cancer. Carcinogenesis 2002;23:1839-49.
de Jong MM, Nolte IM, te Meerman GJ, van der Graaf WT, de Vries EG, Sijmons RH, et al.
Low-penetrance genes and their involvement in colorectal cancer susceptibility. Cancer Epidemiol Biomarkers Prev 2002;11:1332-52.
Houlston RS, Tomlinson IP. Polymorphisms and colorectal tumor risk. Gastroenterology 2001;121:282-301.
Strassburg CP, Vogel A, Kneip S, Tukey RH, Manns MP. Polymorphisms of the human UDP-glucuronosyltransferase (UGT) 1A7 gene in colorectal cancer. Gut 2002;50:851-6.
Doney AS, Lee S, Leese GP, Morris AD, Palmer CN. Increased cardiovascular morbidity and mortality in type 2 diabetes is associated with the glutathione S transferase theta-null genotype: A Go-DARTS study. Circulation 2005;111:2927-34.
Wang G, Zhang L, Li Q. Genetic polymorphisms of GSTT1, GSTM1
, and NQO1 genes and diabetes mellitus risk in Chinese population. Biochem Biophys Res Commun 2006;341:310-3.
Kassab A, Msolly A, Lakhdar R, Gharbi O, Miled A. Polymorphisms of glutathione-S-transferases M1, T1, P1 and susceptibility to colorectal cancer in a sample of the Tunisian population. Med Oncol 2014;31:760.
Purcell S, Cherny SS, Sham PC. Genetic Power Calculator: Design of linkage and association genetic mapping studies of complex traits. Bioinformatics 2003;19:149-50.
Kiyohara C. Genetic polymorphism of enzymes involved in xenobiotic metabolism and the risk of colorectal cancer. J Epidemiol 2000;10:349-60.
Gong M, Dong W, Shi Z, Xu Y, Ni W, An R. Genetic polymorphisms of GSTM1
, GSTT1, and GSTP1 with prostate cancer risk: A meta-analysis of 57 studies. PLoS One 2012;7:e50587.
Giuliano DP, Luiz Alexandre VM, Fabrı'cio RS. Glutathione S-transferases: An overview in cancer research expert opin. Drug MetabToxicol 2010;6:153-70.
Economopoulos KP, Sergentanis TN. GSTM1
, GSTT1, GSTP1, GSTA1 and colorectal cancer risk: A comprehensive meta-analysis. Eur J Cancer 2010;46:1617-31.
Wang J, Jiang J, Zhao Y, Gajalakshmi V, Kuriki K, Suzuki S, et al.
Genetic polymorphisms of glutathione S-transferase genes and susceptibility to colorectal cancer: A case-control study in an Indian population. Cancer Epidemiol 2011;35:66-72.
van der Logt EM, Bergevoet SM, Roelofs HM, van Hooijdonk Z, te Morsche RH, Wobbes T, et al.
Genetic polymorphisms in UDP-glucuronosyltransferases and glutathione S-transferases and colorectal cancer risk. Carcinogenesis 2004;25:2407-15.
Hezova R, Bienertova-Vasku J, Sachlova M, Brezkova V, Vasku A, Svoboda M, et al.
Common polymorphisms in GSTM1
, GSTT1, GSTP1, GSTA1 and susceptibility to colorectal cancer in the Central European population. Eur J Med Res 2012;17:17.
Cotterchio M, Boucher BA, Manno M, Gallinger S, Okey AB, Harper PA. Red meat intake, doneness, polymorphisms in genes that encode carcinogen-metabolizing enzymes, and colorectal cancer risk. Cancer Epidemiol Biomarkers Prev 2008;17:3098-107.
Lampe JW, Peterson S. Brassica, biotransformation and cancer risk: Genetic polymorphisms alter the preventive effects of cruciferous vegetables. J Nutr 2002;132:2991-4.
Butler WJ, Ryan P, Roberts-Thomson IC. Metabolic genotypes and risk for colorectal cancer. J Gastroenterol Hepatol 2001;16:631-5.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]
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