ANTIBODIES TO BENZO[A]PYRENE AND POLYMORPHISMS OF CYP1A1*2A, CYP1A2*1F, GSTT1, AND GSTM1 GENES IN HEALTHY MEN AND LUNG CANCER PATIENTS

Some genetic polymorphisms of CYP and GST enzymes metabolizing low-molecular weight xenobiotics may represent endogenous risk factors for carcinogenesis. However, possible relationships between the enzyme activities, amounts of carcinogen adducts and synthesis of anticarcinogen antibodies in humans...

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Autores principales: A. N. Glushkov, E. G. Polenok, L. A. Gordeeva, S. A. Mun, V. A. Titov, M. V. Kostyanko, I. A. Vafin, S. E. Ragozhina
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spelling oai:doaj.org-article:8766570510e04510be3784cc93c4bc792021-11-18T08:03:45ZANTIBODIES TO BENZO[A]PYRENE AND POLYMORPHISMS OF CYP1A1*2A, CYP1A2*1F, GSTT1, AND GSTM1 GENES IN HEALTHY MEN AND LUNG CANCER PATIENTS1563-06252313-741X10.15789/1563-0625-2016-1-41-50https://doaj.org/article/8766570510e04510be3784cc93c4bc792016-04-01T00:00:00Zhttps://www.mimmun.ru/mimmun/article/view/987https://doaj.org/toc/1563-0625https://doaj.org/toc/2313-741XSome genetic polymorphisms of CYP and GST enzymes metabolizing low-molecular weight xenobiotics may represent endogenous risk factors for carcinogenesis. However, possible relationships between the enzyme activities, amounts of carcinogen adducts and synthesis of anticarcinogen antibodies in humans (including cancer patients) are still poorly studied. The purpose of this study was to identify possible associations between occurrence of antibodies against benzo[a]pyrene, and frequency of genetic polymorphisms of CYP1A1*2A, CYP1A2*1F, GSTT1, GSTM1 in healthy men and in lung cancer patients. Materials and methods. We have examined 203 men with non-small cell lung cancer and 267 apparently healthy donors without respiratory diseases. A non-competitive solid phase immunoassay of antibodies to benzo[a]pyrene was performed. Analysis of polymorphic loci within CYP1A1 (rs4646903), CYP1A2 (rs762551), GSTP1 (rs1695, rs1138272) was performed by means of real-time PCR using TaqMan technology. Null-alleles of GSTM1 (del), GSTT1 (del) genes were detected by multiplex PCR with real-time fluorescent assay. Results. Among the lung cancer patients, the proportion of cases with a high level of IgG antibodies to benzo[a]pyrene in carriers of GSTT1+ and GSTM1+ in conjunction with the CYP1A2*1F C allele was significantly greater than in AA homozygotes CYP1A2*1F. The risk of lung cancer was increased to 5.5 in carriers of CYP1A2*1F C allele combined with GSTT1+ and GSTM1+ at high levels of IgG antibodies to benzo [a] pyrene. In healthy male donors, we have not found differences between the incidence of low and high levels of IgG anti-benzo[a]pyrene antibodies in the carriers of certain CYP1A1*2A, CYP1A2*1F, GSTT1 and GSTM1 genotypes. Conclusions. We have first reported a relationship between CYP1 and GST gene polymorphisms and specific immune response to chemical carcinogens in lung cancer patients. Immunoassays of IgG antibodies to benzo[a]pyrene combined with molecular biology studies of CYP1 and GST are recommended for the cancer risk assessment.A. N. GlushkovE. G. PolenokL. A. GordeevaS. A. MunV. A. TitovM. V. KostyankoI. A. VafinS. E. RagozhinaSPb RAACIarticleantibodiesbenzo[a]pyrenegenes polymorphismscarcinogenesislung cancerImmunologic diseases. AllergyRC581-607RUMedicinskaâ Immunologiâ, Vol 18, Iss 1, Pp 41-50 (2016)
institution DOAJ
collection DOAJ
language RU
topic antibodies
benzo[a]pyrene
genes polymorphisms
carcinogenesis
lung cancer
Immunologic diseases. Allergy
RC581-607
spellingShingle antibodies
benzo[a]pyrene
genes polymorphisms
carcinogenesis
lung cancer
Immunologic diseases. Allergy
RC581-607
A. N. Glushkov
E. G. Polenok
L. A. Gordeeva
S. A. Mun
V. A. Titov
M. V. Kostyanko
I. A. Vafin
S. E. Ragozhina
ANTIBODIES TO BENZO[A]PYRENE AND POLYMORPHISMS OF CYP1A1*2A, CYP1A2*1F, GSTT1, AND GSTM1 GENES IN HEALTHY MEN AND LUNG CANCER PATIENTS
description Some genetic polymorphisms of CYP and GST enzymes metabolizing low-molecular weight xenobiotics may represent endogenous risk factors for carcinogenesis. However, possible relationships between the enzyme activities, amounts of carcinogen adducts and synthesis of anticarcinogen antibodies in humans (including cancer patients) are still poorly studied. The purpose of this study was to identify possible associations between occurrence of antibodies against benzo[a]pyrene, and frequency of genetic polymorphisms of CYP1A1*2A, CYP1A2*1F, GSTT1, GSTM1 in healthy men and in lung cancer patients. Materials and methods. We have examined 203 men with non-small cell lung cancer and 267 apparently healthy donors without respiratory diseases. A non-competitive solid phase immunoassay of antibodies to benzo[a]pyrene was performed. Analysis of polymorphic loci within CYP1A1 (rs4646903), CYP1A2 (rs762551), GSTP1 (rs1695, rs1138272) was performed by means of real-time PCR using TaqMan technology. Null-alleles of GSTM1 (del), GSTT1 (del) genes were detected by multiplex PCR with real-time fluorescent assay. Results. Among the lung cancer patients, the proportion of cases with a high level of IgG antibodies to benzo[a]pyrene in carriers of GSTT1+ and GSTM1+ in conjunction with the CYP1A2*1F C allele was significantly greater than in AA homozygotes CYP1A2*1F. The risk of lung cancer was increased to 5.5 in carriers of CYP1A2*1F C allele combined with GSTT1+ and GSTM1+ at high levels of IgG antibodies to benzo [a] pyrene. In healthy male donors, we have not found differences between the incidence of low and high levels of IgG anti-benzo[a]pyrene antibodies in the carriers of certain CYP1A1*2A, CYP1A2*1F, GSTT1 and GSTM1 genotypes. Conclusions. We have first reported a relationship between CYP1 and GST gene polymorphisms and specific immune response to chemical carcinogens in lung cancer patients. Immunoassays of IgG antibodies to benzo[a]pyrene combined with molecular biology studies of CYP1 and GST are recommended for the cancer risk assessment.
format article
author A. N. Glushkov
E. G. Polenok
L. A. Gordeeva
S. A. Mun
V. A. Titov
M. V. Kostyanko
I. A. Vafin
S. E. Ragozhina
author_facet A. N. Glushkov
E. G. Polenok
L. A. Gordeeva
S. A. Mun
V. A. Titov
M. V. Kostyanko
I. A. Vafin
S. E. Ragozhina
author_sort A. N. Glushkov
title ANTIBODIES TO BENZO[A]PYRENE AND POLYMORPHISMS OF CYP1A1*2A, CYP1A2*1F, GSTT1, AND GSTM1 GENES IN HEALTHY MEN AND LUNG CANCER PATIENTS
title_short ANTIBODIES TO BENZO[A]PYRENE AND POLYMORPHISMS OF CYP1A1*2A, CYP1A2*1F, GSTT1, AND GSTM1 GENES IN HEALTHY MEN AND LUNG CANCER PATIENTS
title_full ANTIBODIES TO BENZO[A]PYRENE AND POLYMORPHISMS OF CYP1A1*2A, CYP1A2*1F, GSTT1, AND GSTM1 GENES IN HEALTHY MEN AND LUNG CANCER PATIENTS
title_fullStr ANTIBODIES TO BENZO[A]PYRENE AND POLYMORPHISMS OF CYP1A1*2A, CYP1A2*1F, GSTT1, AND GSTM1 GENES IN HEALTHY MEN AND LUNG CANCER PATIENTS
title_full_unstemmed ANTIBODIES TO BENZO[A]PYRENE AND POLYMORPHISMS OF CYP1A1*2A, CYP1A2*1F, GSTT1, AND GSTM1 GENES IN HEALTHY MEN AND LUNG CANCER PATIENTS
title_sort antibodies to benzo[a]pyrene and polymorphisms of cyp1a1*2a, cyp1a2*1f, gstt1, and gstm1 genes in healthy men and lung cancer patients
publisher SPb RAACI
publishDate 2016
url https://doaj.org/article/8766570510e04510be3784cc93c4bc79
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