Taruna Rajagopal1, Arun Seshachalam2, Krishna Kumar Rathnam3, Arunachalam Jothi4, Srikanth Talluri5,6, Sivaramakrishnan Venkatabalasubramanian7, Nageswara Rao Dunna8. 1. Cancer Genomics Laboratory, Department of Biotechnology, School of Chemical and Biotechnology, SASTRA - Deemed University, Thanjavur, 613 401, India. 2. Department of Medical and Paediatric Oncology, Dr.G.V.N Cancer Institute, Singarathope, Trichy, 620 008, India. 3. Department of Hemato Oncology - Medical Oncology and Bone Marrow Transplantation, Meenakshi Mission Hospital & Research Centre, Madurai, 625 107, India. 4. Department of Bioinformatics, School of Chemical and Biotechnology, SASTRA - Deemed University, Thanjavur, 613 401, India. 5. Dana Farber Cancer Institute, Boston, MA, 02215, USA. 6. Veterans Administration Boston Healthcare System, West Roxbury, MA, 02132, USA. 7. Department of Genetic Engineering, Faculty of Engineering and Technology, SRM Institute of Medical Science and Technology, Kattankulathur Campus, Chennai, 603 203, India. 8. Cancer Genomics Laboratory, Department of Biotechnology, School of Chemical and Biotechnology, SASTRA - Deemed University, Thanjavur, 613 401, India. dnrao@biotech.sastra.edu.
Abstract
BACKGROUND: Functional variants of the xenobiotic-metabolizing genes (XMG) might modulate breast cancer (BC) risk by altering the rate of metabolism and clearance of myriad types of potent carcinogens from the breast tissue. Despite mounting evidence on the role of XMG variants on BC risk, the current knowledge regarding their influence on BC development is still fragmentary. METHODS: The present study examined the candidate genetic variants in CYP1A1, NQO1, GST-T1, GST-M1, and GST-P1 in 1002 subjects (502 BC patients and 500 disease-free women). PCR-RFLP was employed to genotype the mono-nucleotide variation in CYP1A1, NQO1, and GST-P1, and allele-specific PCR was used to detect the deletion polymorphism in GST-T1 and GST-M1 genes. RESULTS: Regarding CYP1A1-M1 polymorphism, the heterozygous TC and mutant CC genotype conferred 1.47-fold (95% CI 1.13-1.91, p = 0.004) and 1.84-fold (95% CI 1.17-2.91, p = 0.009) elevated risk of BC. GST-T1 null genotype was associated with increased BC risk (OR 1.47; 95% CI 1.02-2.11, p = 0.037). For the NQO1 C609T variant, the mutant T allele was associated with BC risk with an odds ratio of 1.22 (95% CI 1.02-1.48, p = 0.034). Combinatorial analysis indicated that the presence of NQO1*2 (CT), CYP1A1-M1 (CC), and GST-P1 rs1695 (AG) genotypes conferred 16.7-fold elevated risk of BC (95% CI 3.65-76.85; p < 0.001). Moreover, GST-M1 null genotype was associated with the development of larger primary breast tumors. CONCLUSION: Xenobiotic-metabolizing gene polymorphisms may play a crucial role in mammary carcinogenesis in South Indian women.
BACKGROUND: Functional variants of the xenobiotic-metabolizing genes (XMG) might modulate breast cancer (BC) risk by altering the rate of metabolism and clearance of myriad types of potent carcinogens from the breast tissue. Despite mounting evidence on the role of XMG variants on BC risk, the current knowledge regarding their influence on BC development is still fragmentary. METHODS: The present study examined the candidate genetic variants in CYP1A1, NQO1, GST-T1, GST-M1, and GST-P1 in 1002 subjects (502 BC patients and 500 disease-free women). PCR-RFLP was employed to genotype the mono-nucleotide variation in CYP1A1, NQO1, and GST-P1, and allele-specific PCR was used to detect the deletion polymorphism in GST-T1 and GST-M1 genes. RESULTS: Regarding CYP1A1-M1 polymorphism, the heterozygous TC and mutant CC genotype conferred 1.47-fold (95% CI 1.13-1.91, p = 0.004) and 1.84-fold (95% CI 1.17-2.91, p = 0.009) elevated risk of BC. GST-T1 null genotype was associated with increased BC risk (OR 1.47; 95% CI 1.02-2.11, p = 0.037). For the NQO1 C609T variant, the mutant T allele was associated with BC risk with an odds ratio of 1.22 (95% CI 1.02-1.48, p = 0.034). Combinatorial analysis indicated that the presence of NQO1*2 (CT), CYP1A1-M1 (CC), and GST-P1 rs1695 (AG) genotypes conferred 16.7-fold elevated risk of BC (95% CI 3.65-76.85; p < 0.001). Moreover, GST-M1 null genotype was associated with the development of larger primary breast tumors. CONCLUSION: Xenobiotic-metabolizing gene polymorphisms may play a crucial role in mammary carcinogenesis in South Indian women.
Entities:
Keywords:
Breast cancer; CYP1A1; GST-M1; GST-P1; GST-T1; NQO1; Polymorphisms
Authors: S A Eldakroory; DA El Morsi; R H Abdel-Rahman; S Roshdy; M S Gouida; E O Khashaba Journal: Hum Exp Toxicol Date: 2017-01-08 Impact factor: 2.903
Authors: Lukas A Hefler; Clemens B Tempfer; Christoph Grimm; Antje Lebrecht; Eva Ulbrich; Georg Heinze; Sepp Leodolter; Christian Schneeberger; Manfred W Mueller; Axel Muendlein; Heinz Koelbl Journal: Cancer Date: 2004-07-15 Impact factor: 6.860