The Effect of <i>CYP, GST,</i> and <i>SULT</i> Polymorphisms and Their Interaction with Smoking on the Risk of Hepatocellular Carcinoma

Boccia, Stefania; Miele, Luca; Panic, Nikola; Turati, Federica; Arzani, Dario; Cefalo, Consuelo; Amore, Rosarita; Bulajic, Milutin; Pompili, Maurizio; Rapaccini, Gianlodovico; Gasbarrini, Antonio; La Vecchia, Carlo; Grieco, Antonio

doi:https://doi.org/10.1155/2015/179867

BioMed Research International

On this page

Abstract Introduction Methods Results Discussion Acknowledgments References Copyright Related Articles

Special Issue

Screening for Complex Diseases and Personalized Health Care

View this Special Issue

Research Article | Open Access

Volume 2015 | Article ID 179867 | https://doi.org/10.1155/2015/179867

The Effect of CYP, GST, and SULT Polymorphisms and Their Interaction with Smoking on the Risk of Hepatocellular Carcinoma

Stefania Boccia,^1,2Luca Miele,^3,4Nikola Panic,^1,5Federica Turati,⁶Dario Arzani,¹Consuelo Cefalo,³Rosarita Amore,¹Milutin Bulajic,^5,7Maurizio Pompili,⁸Gianlodovico Rapaccini,^3,4Antonio Gasbarrini,⁸and Carlo La Vecchia⁹ et al.

Academic Editor: Paolo Boffetta

Received16 Apr 2014

Revised19 Jun 2014

Accepted19 Jun 2014

Published14 Jan 2015

Abstract

Aim. The aim of our study was to assess whether selected single nucleotide polymorphisms of CYP1A1 and 2E1, GSTM1, GSTT1, and SULT1A1 influence susceptibility towards HCC, considering their interaction with cigarette smoking. Methods. We recruited HCC cases and controls among patients admitted to the hospital “Agostino Gemelli,” from January 2005 until July 2010. Odds ratios (OR) of HCC were derived from unconditional multiple logistic regression. Gene-gene and gene-smoking interaction were quantified by computing the attributable proportion (AP) due to biological interaction. Results. The presence of any CYP2E15B variant allele (OR: 0.23; 95% CI: 0.06-0.71) and CYP2E16 variant allele (OR: 0.08; 95% CI: 0.01–0.33) was inversely related to HCC. There was a borderline increased risk among carriers of combined CYP1A12A and SULT1A1 variant alleles (OR: 1.67; 95% CI: 0.97–3.24). A significant biological interaction was observed between GSTT1 and smoking (AP = 0.48; 95% CI: 0.001–0.815), with an OR of 3.13 (95% CI: 1.69–5.82), and borderline significant interaction was observed for SULT1A1 and smoking (AP = 0.36; 95% CI: −0.021–0.747), with an OR of 3.05 (95% CI: 1.73–5.40). Conclusion. CYP2E15B and CYP2E16 polymorphisms have a favourable effect on the development of HCC, while polymorphisms of GSTT1 and SULT1A1 might play role in increasing the susceptibility among smokers.

1. Introduction

Hepatocellular carcinoma (HCC) is currently the sixth most common cancer and the third cause of cancer deaths worldwide [1]. Its prognosis remains poor, with a 5-year survival rate less than 20% in Europe [2]. Risk factors for HCC include infection with hepatitis B (HBV) and hepatitis C viruses (HCV), history of diabetes mellitus, nonalcoholic fatty liver disease and cirrhosis, heavy alcohol consumption, and cigarette smoking [3–5]. Coffee consumption appears to have a favorable effect [6]. Further, genetic factors appear to modulate the individual susceptibility as the siblings of HCC individuals are more prone to develop the HCC even in the absence of HBV infection [7]. So far, several single nucleotide polymorphisms (SNPs) have been investigated in association with HCC, with contradictory results [8].

As the liver is the main metabolic organ, the SNPs related to genes encoding carcinogen-metabolizing enzymes represent key target candidates for association analyses. Cytochrome P-450 (CYP) is a superfamily of monooxygenases responsible for phase I enzyme reactions, preparing substrates for phase II conjugation reactions, but they can also lead to the metabolic activation of toxic or carcinogenic compounds [9]. The glutathione S-transferases (GSTs) are a gene superfamily coding phase II enzymes that detoxify free radicals in tobacco smoke, products of oxidative stress, and polycyclic aromatic hydrocarbons [10]. Sulfotransferase (SULT) catalyzes sulfonate conjugation to detoxify the procarcinogens to metabolites, which are easily eliminated from the body [11]. Polymorphisms in these genes, their combination, and interaction with environmental factors have the potential to lead to increased susceptibility to HCC. While some studies investigated the effect of GST and CYP genes on HCC, as well as their combination and interaction with smoking [12, 13], little information is available on the effect of SULT1A1.

The aim of our study was to assess whether the selected SNPs of CYP1A1 and 2E1, GSTM1, GSTT1, and SULT1A1 genes influence individual susceptibility to HCC, also considering their combination and interaction with cigarette smoking.

2. Methods

2.1. Study Population

Study participants were recruited among patients admitted to the teaching hospital “Agostino Gemelli” of the Università Cattolica del Sacro Cuore (Rome, Italy) from January 2005 until July 2010, and eligibility was restricted to white individuals born in Italy. Cases were 221 patients with HCC recruited among subjects referred to the Outpatient Liver Unit of the hospital. The diagnosis of HCC was performed according the AASLD guidelines [14]. The control group included 290 patients from the same hospital with a broad range of diagnoses, enrolled during the same time period. In closer detail, around 50% of the controls were outpatients, and the remaining were patients undergoing surgical interventions (laparoscopic cholecystectomy, appendicitis, and inguinal hernia) or admitted for a wide spectrum of other nonneoplastic conditions (elderly patients on physical-therapy rehabilitation after stroke or orthopedic injuries). Written informed consent was obtained from all study subjects. The study was conducted according to the Declaration of Helsinki and was approved by the Ethical Committee of Università Cattolica del Sacro Cuore.

HCC cases and controls were interviewed by trained physicians using a structured questionnaire to collect information on demographics, medical history, and lifestyle habits including smoking history. Questions about lifestyle habits focused on the time period ending one year prior to diagnosis for cases and on the year prior to the interview date for controls.

2.2. Genotyping Methods

DNA was extracted from the peripheral blood lymphocytes of each participating subject. GSTM1 and GSTT1 null alleles were identified using a multiplex-polymerase chain reaction- (PCR-) based method [15]. The polymorphic site at nucleotide 638 in exon 7 (Arg213His (2 allele), rs9282861) of the SULT1A1 gene was genotyped by PCR-restriction fragment length polymorphisms (RFLP) analysis as described by Coughtrie et al. [16]. CYP1A1 3′-flanking region MspI polymorphism (CYP1A12A allele, rs4646903), CYP2E1 PstI/RsaI polymorphism (CYP2E15B allele, rs3813867 (PstI)), and CYP2E1 DraI (5A or 6 alleles, rs6413432) were also determined by PCR-RFLP analyses. Quality control for each genotyping was performed in each experiment, and 10% of the total samples were randomly selected and reanalyzed with 100% concordance. All laboratory procedures were carried out blindly to case-control status.

2.3. Statistical Analysis

Hardy-Weinberg equilibrium (HWE) was tested for the control SNPs. Odds ratios (OR) of HCC and corresponding 95% confidence intervals (CI) according to analyzed polymorphisms were derived from unconditional multiple logistic regression models [17] using dominant model for carriers of the mutated allele, including terms for age and sex. When cell sizes were small (<5), exact logistic regression was used [18].

We also examined the possible confounding effect of smoking, alcohol, and chronic infection with HBV and/or HCV. However, models including these covariates yielded very similar results; thus, given the small numbers in some strata, only the age- and sex-adjusted estimates were presented.

Gene-gene interaction analysis was conducted, using as a reference group the homozygous wild-type individuals for both genes, while for gene-environment interaction analyses, the reference group was wild-type homozygotes not exposed to the environmental risk factor. Biological interaction between two genes was estimated using departure from additivity of effects as the criterion of interaction, as proposed by Rothman [19]. To quantify the amount of interaction, the attributable proportion (AP) due to interaction was calculated together with its 95% CI as described by Andersson et al. [20]. The AP due to interaction is the proportion of individuals among those exposed to the two interacting factors that is attributable to the interaction per se and it is equal to 0 in the absence of a biological interaction [19]. In order to test for more than multiplicative effect among two genes, the likelihood ratio test was used.

The paper has been written according to the STREGA guidelines [21].

3. Results

The demographics, clinical features and lifestyle habits of 221 HCC cases and 290 controls are reported in Table 1. Ever smokers were more common among cases, as well as infection with HBV and/or HCV (Table 1). The genotype frequencies were in HWE ().

Table 2 reports the distribution of the polymorphisms considered among HCC patients and controls. The carriers of c2 variant allele of CYP2E15B polymorphisms were less common in cases (1.8%) than in controls (6.9%) corresponding to an OR of 0.23 (95% CI: 0.06–0.71). Similarly, the frequency of the variant allele of CYP2E16 polymorphism was also less common among cases (1.0%) than controls (10%), with an OR of 0.08 (95% CI: 0.01–0.33) (Table 2). The selected polymorphisms of CYP1A1, GSTM1, GSTT1, and SULT1A1 did not significantly influence susceptibility to HCC.

The gene-gene and gene-smoking interaction results are reported in Tables 3 and 4. We observed a borderline increased risk for HCC among carriers of combined CYP1A12A and SULT1A1 variant alleles as compared to the double wild-type homozygotes (OR = 1.67; 95% CI: 0.97–3.24) (Table 3). A significant interaction was reported between GSTT1 and smoking (AP = 0.48; 95% CI: 0.001–0.815), with an OR of 3.13 (95% CI: 1.69–5.82) for GSTT1 null genotype carriers who were smokers (Table 4). A borderline significant interaction was also observed for SULT1A1 and smoking (AP = 0.36; 95% CI: −0.021–0.747), with an OR of 3.05 (95 CI: 1.73–5.40) for those SULT1A1 variant allele carriers who were smokers (Table 4).

4. Discussion

Our study identified CYP2E15B and CYP2E16 variant alleles associated with a reduced risk of HCC. There was a borderline increased risk for HCC among carriers of combined SULT1A1 and CYP1A12A variant alleles. The polymorphisms in GSTT1 and SULT1A1 are associated with increased susceptibility to smoking-related HCC.

CYP2E1 can activate N-nitrosamines and benzene contained in cigarette smoke [22] and is involved in alcohol-mediated generation of oxidative stress [23]. The expression of CYP2E1 correlates with the generation of hydroxyethyl radicals and lipid peroxidation products [23]. The variant CYP2E15B and CYP2E16 alleles are associated with increased transcription of CYP2E1 [24] that leads to development of HCC by promoting carcinogenesis. No significant association between CYP2E16 and HCC was reported so far [25, 26], while contradictory results were reported for the CYP2E15B variant allele [27–35]. A recent meta-analysis did not find CYP2E15B c2 allele to be associated with HCC [36], also after stratifying among Asians and white. Studies conducted among white individuals, however, were few [26, 30, 35] and included limited numbers of cases.

The favorable effect of both CYP2E1 polymorphisms on HCC development is not consistent with the biological premises implying a promoting role of a high activity enzyme. However, the only study previously conducted in an Italian population [35] on CYP2E15B c2 allele and HCC did report a similar association, indicating a favorable role of the variant allele against HCC which deserves further investigation.

Our results suggest that up to 48% and 36% of HCC cases among smokers carrying, respectively, variant GSTT1 and SULT1A1 alleles occurred because of gene-smoking interaction. However, we could not further stratify these two results according to quantity of smoking, as numbers were low. Smoking is recognized as a risk factor for HCC [3–5] and, together with HBV and HCV, one of the major risk factors in Europe [37], and enzymes coded by GSTT1 and SULT1A1 have their role in the metabolism of tobacco carcinogens. There is therefore a biological ground for possible synergic carcinogenic effect.

There was a borderline synergic effect of SULT1A1 and CYP1A12A polymorphisms in HCC carcinogenesis. The effect of SULT1A1 polymorphism on HCC development has not been investigated so far. It has been reported, however, that an enzyme coded by SULT1A1 variant allele has twofold lower catalytic activity in detoxifying the procarcinogens [38]. The biological significance of variant CYP1A12A variant allele is uncertain, but CYP1A12A has been reported to increase susceptibility to several cancer types, including lung, breast, and cervical cancer [39–41]. There is therefore a rationale for a synergic effect of these two SNPs in HCC carcinogenesis.

In our study, there was no significant association between HCC and alcohol. As most of the cases have hepatitis, this could lead them to stop drinking. Consequently we were unable to perform gene-alcohol interaction analysis. Secondly, we cannot exclude a selection bias. However, since the observed frequencies of the variant alleles of CYP1A12A, as well as the null genotypes of GSTM1 and GSTT1, were in line with those previously reported in the Italian population, a major impact of such bias is unlikely [35, 42]. Thirdly, our study was underpowered to perform gene-gene and gene-interaction analysis.

In conclusion, we report that CYP2E15B and CYP2E16 polymorphisms have a favorable effect on the development of HCC, while the polymorphisms in GSTT1 and SULT1A1 may increase HCC susceptibility among smokers.

Conflict of Interests

The authors declare that there is no conflict of interests regarding the publication of this paper.

Acknowledgments

This work was supported by the contribution of the Italian Association for Cancer Research (AIRC; Grant number 10068). The work of Nikola Panic was supported by the ERAWEB project, funded with support of the European Community. The work of Federica Turati was supported by a fellowship from the Italian Foundation for Cancer Research (FIRC). The work of Luca Miele was supported by MIUR-Università Cattolica del Sacro Cuore “Giovani Ricercatori 2002” and Istituto Toniolo Research Prize. The work of Antonio Grieco was supported by MIUR-Università Cattolica del Sacro Cuore Research Grants Linea D1.

References

International Agency on Research of Cancer, 2012, http://globocan.iarc.fr/Default.aspx.
M. op den Winkel, D. Nagel, J. Sappl et al., “Prognosis of patients with hepatocellular carcinoma. validation and ranking of established staging-systems in a large Western HCC-Cohort,” PLoS ONE, vol. 7, no. 10, Article ID e45066, 2012.
View at: Publisher Site | Google Scholar
S. Chuang, C. L. Vecchia, and P. Boffetta, “Liver cancer: descriptive epidemiology and risk factors other than HBV and HCV infection,” Cancer Letters, vol. 286, no. 1, pp. 9–14, 2009.
View at: Publisher Site | Google Scholar
S. Franceschi, M. Montella, J. Polesel et al., “Hepatitis viruses, alcohol, and tobacco in the etiology of hepatocellular carcinoma in Italy,” Cancer Epidemiology Biomarkers and Prevention, vol. 15, no. 4, pp. 683–689, 2006.
View at: Publisher Site | Google Scholar
F. Turati, R. Talamini, C. Pelucchi et al., “Metabolic syndrome and hepatocellular carcinoma risk,” British Journal of Cancer, vol. 108, no. 1, pp. 222–228, 2013.
View at: Publisher Site | Google Scholar
F. Bravi, C. Bosetti, A. Tavani, S. Gallus, and C. La Vecchia, “Coffee reduces risk for hepatocellular carcinoma: an updated meta-analysis,” Clinical Gastroenterology and Hepatology, vol. 11, no. 11, pp. 1413–1421, 2013.
View at: Publisher Site | Google Scholar
Y. Gao, Q. Jiang, X. Zhou et al., “HBV infection and familial aggregation of liver cancer: an analysis of case-control family study,” Cancer Causes and Control, vol. 15, no. 8, pp. 845–850, 2004.
View at: Publisher Site | Google Scholar
F. Jin, W. J. Xiong, J. C. Jing, Z. Feng, L. S. Qu, and X. Z. Shen, “Evaluation of the association studies of single nucleotide polymorphisms and hepatocellular carcinoma: a systematic review,” Journal of Cancer Research and Clinical Oncology, vol. 137, no. 7, pp. 1095–1104, 2011.
View at: Publisher Site | Google Scholar
J. A. Hasler, “Pharmacogenetics of cytochromes P450,” Molecular Aspects of Medicine, vol. 20, no. 1-2, pp. 12–137, 1999.
View at: Google Scholar
J. D. Hayes and D. J. Pulford, “The glutathione S-transferase supergene family: regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance,” Critical Reviews in Biochemistry and Molecular Biology, vol. 30, no. 6, pp. 445–600, 1995.
View at: Publisher Site | Google Scholar
N. Gamage, A. Barnett, N. Hempel et al., “Human sulfotransferases and their role in chemical metabolism,” Toxicological Sciences, vol. 90, no. 1, pp. 5–22, 2006.
View at: Publisher Site | Google Scholar
K. Song, J. Yi, X. Shen, and Y. Cai, “Genetic polymorphisms of glutathione S- transferase genes GSTM1, GSTT1 and risk of hepatocellular carcinoma,” PLoS ONE, vol. 7, no. 11, Article ID e48924, 2012.
View at: Publisher Site | Google Scholar
L. Yu, L. Sun, Y. Jiang, B. Lu, D. Sun, and L. Zhu, “Interactions between CYP1A1 polymorphisms and cigarette smoking are associated with the risk of hepatocellular carcinoma: evidence from epidemiological studies,” Molecular Biology Reports, vol. 39, no. 6, pp. 6641–6646, 2012.
View at: Publisher Site | Google Scholar
J. Bruix and M. Sherman, “Management of Hepatocellular carcinoma,” Hepatology, vol. 42, no. 5, pp. 1208–1236, 2005.
View at: Publisher Site | Google Scholar
M. Arand, R. Mühlbauer, J. Hengstler et al., “A multiplex polymerase chain reaction protocol for the simultaneous analysis of the glutathione S-transferase GSTM1 and GSTT1 polymorphisms,” Analytical Biochemistry, vol. 236, no. 1, pp. 184–186, 1996.
View at: Publisher Site | Google Scholar
M. W. Coughtrie, R. A. Gilissen, B. Shek et al., “Phenol sulphotransferase SULT1A1 polymorphism: molecular diagnosis and allele frequencies in Caucasian and African populations,” Biochemical Journal, vol. 337, no. 1, pp. 45–49, 1999.
View at: Publisher Site | Google Scholar
N. E. Breslow and N. E. Day, Statistical Methods in Cancer Research, Vol. 1. The Analysis of Case-Control Studies, IARC, Lyon, France, 1980.
K. F. Hirji, C. R. Mehta, and N. R. Patel, “Exact inference for matched case-control studies,” Biometrics. Journal of the Biometric Society, vol. 44, no. 3, pp. 803–814, 1988.
View at: Publisher Site | Google Scholar | Zentralblatt MATH | MathSciNet
K. J. Rothman, “Measuring interactions,” in Epidemiology: An Introduction, K. J. Rothman, Ed., pp. 168–190, Oxford University Press, New York, NY, USA, 2002.
View at: Google Scholar
T. Andersson, L. Alfredsson, H. Källberg, S. Zdravkovic, and A. Ahlbom, “Calculating measures of biological interaction,” European Journal of Epidemiology, vol. 20, no. 7, pp. 575–579, 2005.
View at: Publisher Site | Google Scholar
J. Little, J. P. T. Higgins, J. P. A. Ioannidis et al., “Strengthening the reporting of genetic association studies (STREGA): an extension of the STROBE statement,” Italian Journal of Public Health, vol. 6, no. 3, pp. 238–255, 2009.
View at: Google Scholar
F. P. Guengerich, D.-H. Kim, and M. Iwasaki, “Role of human cytochrome P-450 IIE1 in the oxidation of many low molecular weight cancer suspects,” Chemical Research in Toxicology, vol. 4, no. 2, pp. 168–179, 1991.
View at: Publisher Site | Google Scholar
E. Albano, P. Clot, M. Morimoto, A. Tomasi, M. Ingelman-Sundberg, and S. W. French, “Role of cytochrome P4502E1-dependent formation of hydroxyethyl free radical in the development of liver damage in rats intragastrically fed with ethanol,” Hepatology, vol. 23, no. 1, pp. 155–163, 1996.
View at: Publisher Site | Google Scholar
S.-M. Wang, A.-P. Zhu, D. Li, Z. Wang, P. Zhang, and G. Zhang, “Frequencies of genotypes and alleles of the functional SNPs in CYP2C19 and CYP2E1 in mainland chinese kazakh, uygur and han populations,” Journal of Human Genetics, vol. 54, no. 6, pp. 372–375, 2009.
View at: Publisher Site | Google Scholar
M.-W. Yu, A. Gladek-Yarborough, S. Chiamprasert et al., “Cytochrome P450 2E1 and glutathione S-transferase M1 polymorphisms and susceptibility to hepatocellular carcinoma,” Gastroenterology, vol. 109, no. 4, pp. 1266–1273, 1995.
View at: Publisher Site | Google Scholar
N. A. Wong, F. Rae, K. J. Simpson, G. D. Murray, and D. J. Harrison, “Genetic polymorphisms of cytochrome p4502E1 and susceptibility to alcoholic liver disease and hepatocellular carcinoma in a white population: a study and literature review, including meta-analysis,” Journal of Clinical Pathology—Molecular Pathology, vol. 53, no. 2, pp. 88–93, 2000.
View at: Publisher Site | Google Scholar
M. Munaka, K. Kohshi, T. Kawamoto et al., “Genetic polymorphisms of tobacco- and alcohol-related metabolizing enzymes and the risk of hepatocellular carcinoma,” Journal of Cancer Research and Clinical Oncology, vol. 129, no. 6, pp. 355–360, 2003.
View at: Publisher Site | Google Scholar
T. Koide, T. Ohno, X. E. Huang et al., “HBV/HCV infection, alcohol, tobacco and genetic polymorphisms for hepatocellular carcinoma in Nagoya, Japan,” Asian Pacific Journal of Cancer Prevention, vol. 1, no. 3, pp. 237–243, 2000.
View at: Google Scholar
X. P. Ye, T. Peng, T. W. Liu et al., “The effect of interaction between alcohol drinking and polymorphisms of cytochrome P450 2E1 on the susceptibility of Hepatocellular carcinoma in Guangxi region,” Journal of Guangxi Medical University, vol. 25, no. 4, pp. 493–495, 2008 (Chinese).
View at: Google Scholar
J. M. Ladero, J. A. Agúndez, A. Rodríguez-Lescure, M. Diaz-Rubio, and J. Benítez, “RsaI polymorphism at the cytochrome P4502E1 locus and risk of hepatocellular carcinoma,” Gut, vol. 39, no. 2, pp. 330–333, 1996.
View at: Publisher Site | Google Scholar
T. Imaizumi, Y. Higaki, M. Hara et al., “Interaction between cytochrome P450 1A2 genetic polymorphism and cigarette smoking on the risk of hepatocellular carcinoma in a Japanese population,” Carcinogenesis, vol. 30, no. 10, pp. 1729–1734, 2009.
View at: Publisher Site | Google Scholar
N. A. Wong, F. Rae, K. J. Simpson, G. D. Murray, and D. J. Harrison, “Genetic polymorphisms of cytochrome p4502E1 and susceptibility to alcoholic liver disease and hepatocellular carcinoma in a white population: a study and literature review, including meta-analysis,” Molecular Pathology, vol. 53, no. 2, pp. 88–93, 2000.
View at: Publisher Site | Google Scholar
S. Z. Yu, X. E. Huang, T. Koide et al., “Hepatitis B and C viruses infection, lifestyle and genetic polymorphisms as risk factors for hepatocellular carcinoma in Haimen, China,” Japanese Journal of Cancer Research, vol. 93, no. 12, pp. 1287–1292, 2002.
View at: Publisher Site | Google Scholar
H. S. Lee, J. H. Yoon, S. Kamimura et al., “Lack of association of cytochrome P450 2E1 genetic polymorphisms with the risk of human hepatocellular carcinoma,” International Journal of Cancer, vol. 71, no. 5, pp. 737–740, 1997.
View at: Google Scholar
L. Silvestri, L. Sonzogni, A. De Silvestri et al., “CYP enzyme polymorphisms and susceptibility to HCV-related chronic liver disease and liver cancer,” International Journal of Cancer, vol. 104, no. 3, pp. 310–317, 2003.
View at: Publisher Site | Google Scholar
C. Liu, H. Wang, C. Pan, J. Shen, and Y. Liang, “CYP2E1 PstI/RsaI polymorphism and interaction with alcohol consumption in hepatocellular carcinoma susceptibility: evidence from 1,661 cases and 2,317 controls,” Tumour Biology, vol. 33, no. 4, pp. 979–984, 2012.
View at: Publisher Site | Google Scholar
D. Trichopoulos, C. Bamia, P. Lagiou et al., “Hepatocellular carcinoma risk factors and disease burden in a European cohort: a nested case-control study,” Journal of the National Cancer Institute, vol. 103, no. 22, pp. 1686–1695, 2011.
View at: Publisher Site | Google Scholar
S. Nowell, C. B. Ambrosone, S. Ozawa et al., “Relationship of phenol sulfotransferase activity (SULT1A1) genotype to sulfotransferase phenotype in platelet cytosol,” Pharmacogenetics, vol. 10, no. 9, pp. 789–797, 2000.
View at: Publisher Site | Google Scholar
T. Juárez-Cedillo, M. Vallejo, J. M. Fragoso et al., “The risk of developing cervical cancer in Mexican women is associated to CYP1A1 MspI polymorphism,” European Journal of Cancer, vol. 43, no. 10, pp. 1590–1595, 2007.
View at: Publisher Site | Google Scholar
A. Shin, D. Kang, J. Y. Choi et al., “Cytochrome P450 1A1 (CYP1A1) polymorphisms and breast cancer risk in Korean women,” Experimental and Molecular Medicine, vol. 39, no. 3, pp. 361–366, 2007.
View at: Publisher Site | Google Scholar
P. Zhan, Q. Wang, Q. Qian, S. Wei, and L. Yu, “CYP1A1 MspI and exon7 gene polymorphisms and lung cancer risk: an updated meta-analysis and review,” Journal of Experimental and Clinical Cancer Research, vol. 30, no. 1, article 99, 2011.
View at: Publisher Site | Google Scholar
L. Covolo, U. Gelatti, R. Talamini et al., “Alcohol dehydrogenase 3, glutathione S-transferase M1 and T1 polymorphisms, alcohol consumption and hepatocellular carcinoma (Italy),” Cancer Causes and Control, vol. 16, no. 7, pp. 831–838, 2005.
View at: Publisher Site | Google Scholar

Copyright

Copyright © 2015 Stefania Boccia et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

PDF Download Citation

Download other formats

Order printed copies

Views

1602

Downloads

1043

Citations