Metabolic gene polymorphisms and lung cancer risk in non-smokers. An update of the GSEC study.
BACKGROUND
Since genetic factors may play an important role in lung cancer development at low dose carcinogen exposure, non-smokers are a good model to study genetic susceptibility and its interaction with environmental factors.


METHODS
We evaluated the role of the metabolic gene polymorphisms CYP1A1MspI, CYP1A1Ile462Val, GSTM1, and GSTT1 in non-smoker lung cancer patients from the International Collaborative Study on Genetic Susceptibility to Environmental Carcinogens (GSEC). Non-smokers (defined as subjects who never smoked on a regular basis) were selected from the GSEC database. We pooled the raw data from 21 case-control studies for a total of 2764 Caucasians (555 cases and 2209 controls) and 383 Asians (113 cases and 270 controls). Tests of heterogeneity and of inclusion bias were performed.


RESULTS
A significant association between lung cancer and CYP1A1Ile462Val polymorphism was observed in Caucasians (adjusted OR=2.04, 95% CI 1.17-3.54). GSTT1 deletion seems to be a risk factor for lung cancer in Caucasian non smokers only when the analysis was restricted to studies including healthy controls (adjusted OR=1.66, 95% CI 1.12-2.46). A protective effect on lung cancer was observed with the combination of CYP1A1 wild type, GSTM1 null, and GSTT1 non-null genotypes. None of the analysed polymorphisms were associated with lung cancer in Asian non-smokers.


CONCLUSIONS
Our analysis confirms previous findings that CYP1A1Ile462Val polymorphism may play a role in lung carcinogenesis in Caucasian non-smokers.
Raimondi
Sara
S
Fondazione Policlinico IRCCS, Molecular and Genetic Epidemiology Unit, via Pace 9, 20122-Milano, Italy.
Boffetta
Paolo
P
Anttila
Sisko
S
Bröckmoller
Jürgen
J
Butkiewicz
Dorota
D
Cascorbi
Ingolf
I
Clapper
Margie L
ML
Dragani
Tommaso A
TA
Garte
Seymour
S
Gsur
Andre
A
Haidinger
Gerald
G
Hirvonen
Ari
A
Ingelman-Sundberg
Magnus
M
Kalina
Ivan
I
Lan
Qing
Q
Leoni
Vera Piera
VP
Le Marchand
Loïc
L
London
Stephanie J
SJ
Neri
Monica
M
Povey
Andrew C
AC
Rannug
Agneta
A
Reszka
Edyta
E
Ryberg
David
D
Risch
Angela
A
Romkes
Marjorie
M
Ruano-Ravina
Alberto
A
Schoket
Bernadette
B
Spinola
Monica
M
Sugimura
Haruhiko
H
Wu
Xifeng
X
Taioli
Emanuela
E
D000230:Adenocarcinoma / Q000453:epidemiology / Q000235:genetics; D019943:Amino Acid Substitution; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000235:genetics; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D004781:Environmental Exposure; D020022:Genetic Predisposition to Disease; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000453:epidemiology / Q000235:genetics*; D011110:Polymorphism, Genetic; D044469:Racial Groups; D016540:Smoking Cessation; D014481:United States
D019363:Cytochrome P-450 CYP1A1; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1