CYP1A1, GSTM1, and GSTT1 polymorphisms, smoking, and lung cancer risk in a pooled analysis among Asian populations.
To evaluate the roles of CYP1A1 polymorphisms [Ile 462Val and T 6235C (MspI)] and deletion of GSTM1 and GSTT1 in lung cancer development in Asian populations, a pooled analysis was conducted on 13 existing studies included in Genetic Susceptibility to Environmental Carcinogenesis database. This pooled analysis included 1,971 cases and 2,130 controls. Lung cancer risk was estimated as odds ratios (OR) and 95% confidence intervals (95% CI) using unconditional logistic regression model adjusting for age, sex, and pack-year. The CYP1A1 6235C variant was associated with squamous cell lung cancer (TC versus TT: OR, 1.42; 95% CI, 0.96-2.09; CC versus TT: OR, 1.97; 95% CI, 1.26-3.07; P trend = 0.003). In haplotype analysis, 462Val-6235T and Ile-C haplotypes were associated with lung cancer risk with reference to the Ile-T haplotype (OR, 3.41; 95% CI, 1.78-6.53 and OR, 1.39; 95% CI, 1.12-1.71, respectively). The GSTM1-null genotype increased squamous cell lung cancer risk (OR, 1.36; 95% CI, 1.05-1.77). When the interaction was evaluated with smoking, increasing trend of lung cancer risk as pack-year increased was stronger among those with the CYP1A1 6235 TC/CC genotype compared with those with TT genotype (P interaction = 0.001) and with the GSTM1-null genotype compared with the present type (Pinteraction = 0.08, when no genotype effect with no exposure was assumed). These results suggest that genetic polymorphisms in CYP1A1 and GSTM1 are associated with lung cancer risk in Asian populations. However, further investigation is warranted considering the relatively small sample size when subgroup analyses were done and the lack of environmental exposure data other than smoking.
Lee
Kyoung-Mu
KM
Department of Preventive Medicine, Seoul National University College of Medicine, 28 Yongon-Dong, Chongno-Gu, Seoul 110-799, Korea.
Kang
Daehee
D
Clapper
Margie L
ML
Ingelman-Sundberg
Magnus
M
Ono-Kihara
Masko
M
Kiyohara
Chikako
C
Min
Shen
S
Lan
Qing
Q
Le Marchand
Loic
L
Lin
Pinpin
P
Lung
Maria Li
ML
Pinarbasi
Hatice
H
Pisani
Paola
P
Srivatanakul
Petcharin
P
Seow
Adeline
A
Sugimura
Haruhiko
H
Tokudome
Shinkan
S
Yokota
Jun
J
Taioli
Emanuela
E
D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics*; D016009:Chi-Square Distribution; D019363:Cytochrome P-450 CYP1A1; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D016015:Logistic Models; D008175:Lung Neoplasms / Q000201:enzymology* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D012306:Risk; D012907:Smoking / Q000009:adverse effects*
D019363:Cytochrome P-450 CYP1A1; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1