Combined CYP1A1/GSTM1 at-risk genotypes are overrepresented in squamous cell lung carcinoma patients but underrepresented in elderly tumor-free subjects.
OBJECTIVE
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.
Belogubova
Evgeniya V
EV
Group of Molecular Diagnostics, N.N. Petrov Institute of Oncology, Pesochny-2, 197758 St.-Petersburg, Russia.
Ulibina
Yulia M
YM
Suvorova
Irina K
IK
Kuligina
Ekatherina Sh
ESh
Karpova
Maria B
MB
Shutkin
Vladimir A
VA
Koloskov
Andrey V
AV
Kuchinskiy
Alexandr P
AP
Togo
Alexandr V
AV
Hanson
Kaido P
KP
Hirvonen
Ari
A
Imyanitov
Evgeny N
EN
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008875:Middle Aged; D012307:Risk Factors
D019363:Cytochrome P-450 CYP1A1; D005982:Glutathione Transferase