PURPOSE: Polycyclic aromatic hydrocarbons are activated by cytochrome P450 1A1 (CYP1A1) and inactivated by glutathione S-transferase mu (GSTM1). Therefore, it is expected that a combination of proficient CYP1A1 genotype with deficient GSTM1 variant would result in particularly elevated lung cancer (LC) risk, especially for squamous cell carcinoma (SCC). This study was aimed to validate whether the CYP1A1-C (3801) (CYP1A1*2) allele has an unfavorable significance alone and/or in combination with the GSTM1 deficiency. METHODS: We compared the distribution of CYP1A1 and GSTM1 genotypes in LC patients (n=141), healthy donors (HD, n=204), and elderly tumor-free smokers and non-smokers (ED, n=246). RESULTS: CYP1A1*2 allele carriers demonstrated a clear-cut association with SCC: the adjusted odds ratios (OR) were 2.22 (95% CI=1.06-4.63) and 2.27 (95% CI=1.14-4.52) when HD and ED were used as referents, respectively. CYP1A1*2(+)/GSTM1(-) combined genotypes were overrepresented in the SCC patients (14/70, 20.0%) and underrepresented in the ED (19/246, 7.7%) as compared to the intermediate prevalence in the HD (26/204, 12.7%); the adjusted OR for SCC versus ED reached 3.85 (95% CI=1.43-10.33). CONCLUSIONS: In agreement with some literature data, our results support the concerted role of CYP1A1 and GSTM1 at-risk genotypes in SCC predisposition.
PURPOSE:Polycyclic aromatic hydrocarbons are activated by cytochrome P450 1A1 (CYP1A1) and inactivated by glutathione S-transferase mu (GSTM1). Therefore, it is expected that a combination of proficient CYP1A1 genotype with deficient GSTM1 variant would result in particularly elevated lung cancer (LC) risk, especially for squamous cell carcinoma (SCC). This study was aimed to validate whether the CYP1A1-C (3801) (CYP1A1*2) allele has an unfavorable significance alone and/or in combination with the GSTM1 deficiency. METHODS: We compared the distribution of CYP1A1 and GSTM1 genotypes in LC patients (n=141), healthy donors (HD, n=204), and elderly tumor-free smokers and non-smokers (ED, n=246). RESULTS:CYP1A1*2 allele carriers demonstrated a clear-cut association with SCC: the adjusted odds ratios (OR) were 2.22 (95% CI=1.06-4.63) and 2.27 (95% CI=1.14-4.52) when HD and ED were used as referents, respectively. CYP1A1*2(+)/GSTM1(-) combined genotypes were overrepresented in the SCC patients (14/70, 20.0%) and underrepresented in the ED (19/246, 7.7%) as compared to the intermediate prevalence in the HD (26/204, 12.7%); the adjusted OR for SCC versus ED reached 3.85 (95% CI=1.43-10.33). CONCLUSIONS: In agreement with some literature data, our results support the concerted role of CYP1A1 and GSTM1 at-risk genotypes in SCC predisposition.
Authors: Paolo Vineis; Fabrizio Veglia; Sisko Anttila; Simone Benhamou; Margie L Clapper; Vita Dolzan; David Ryberg; Ari Hirvonen; Pierre Kremers; Loic Le Marchand; Roberta Pastorelli; Agneta Rannug; Marjorie Romkes; Bernadette Schoket; Richard C Strange; Seymour Garte; Emanuela Taioli Journal: Biomarkers Date: 2004 May-Jun Impact factor: 2.658
Authors: Paolo Vineis; Fabrizio Veglia; Simone Benhamou; Dorota Butkiewicz; Ingolf Cascorbi; Margie L Clapper; Vita Dolzan; Aage Haugen; Ari Hirvonen; Magnus Ingelman-Sundberg; Masahiro Kihara; Chikako Kiyohara; Pierre Kremers; Loic Le Marchand; Susumu Ohshima; Roberta Pastorelli; Agneta Rannug; Marjorie Romkes; Bernadette Schoket; Peter Shields; Richard C Strange; Isabelle Stucker; Haruhiko Sugimura; Seymour Garte; Laura Gaspari; Emanuela Taioli Journal: Int J Cancer Date: 2003-05-01 Impact factor: 7.396
Authors: Evgeniya V Belogubova; Alexandr V Togo; Maria B Karpova; Ekatherina Sh Kuligina; Konstantin G Buslova; Julia M Ulibina; Vladimir G Lemehov; Sergey M Romanenko; Vladimir A Shutkin; Kaido P Hanson; Ari Hirvonen; Evgeny N Imyanitov Journal: Lung Cancer Date: 2004-03 Impact factor: 5.705
Authors: José Luis Pérez-Gracia; Alfonso Gúrpide; María Gloria Ruiz-Ilundain; Carlos Alfaro Alegría; Ramon Colomer; Jesús García-Foncillas; Ignacio Melero Bermejo Journal: Clin Transl Oncol Date: 2010-03 Impact factor: 3.405