CYP1A1 T3801 C polymorphism and lung cancer: a pooled analysis of 2451 cases and 3358 controls.
CYP1A1 is involved in the metabolism of benzopyrene, a suspected lung carcinogen; it is therefore conceivable that genetically determined variations in its activity modify individual susceptibility to lung cancer. The role of the CYP1A1 MspI polymorphism in lung cancer has been widely studied but has not been fully clarified. We have included 2,451 cases and 3,358 controls in a pooled analysis of 22 case-control studies on CYP1A1 and lung cancer risk. We found a clear association between the CYP1A1 homozygous MspI restriction fragment length polymorphism (RFLP) and lung cancer risk in Caucasians (age- and gender-adjusted odds ratio = 2.36; 95% confidence interval 1.16-4.81); other associations were weaker or not statistically significant. The association with the homozygous variant was equally strong for squamous cell carcinomas and adenocarcinomas among Caucasians. We analyzed the risk by duration of smoking: for Caucasian subjects with the MspI RFLP combined variants (homozygotes plus heterozygotes), the increase in the risk of lung cancer was steeper than among the individuals with the homozygous reference allele. Our analysis suggests that Caucasians with homozygous variant CYP1A1 polymorphism have a higher risk of lung cancer. The data were more consistent among Caucasians, with a strong association between the homozygous variant in both squamous cell carcinomas and adenocarcinomas, and a stronger association in men than in women. The analyses were more inconsistent and failed to reach statistical significance in Asians. This observation might be due to design specificities or unknown effect modifiers in the Asian studies.
Vineis
Paolo
P
Università degli studi di Torino, Torino, Italy. paolo.vineis@unito.it
Veglia
Fabrizio
F
Benhamou
Simone
S
Butkiewicz
Dorota
D
Cascorbi
Ingolf
I
Clapper
Margie L
ML
Dolzan
Vita
V
Haugen
Aage
A
Hirvonen
Ari
A
Ingelman-Sundberg
Magnus
M
Kihara
Masahiro
M
Kiyohara
Chikako
C
Kremers
Pierre
P
Le Marchand
Loic
L
Ohshima
Susumu
S
Pastorelli
Roberta
R
Rannug
Agneta
A
Romkes
Marjorie
M
Schoket
Bernadette
B
Shields
Peter
P
Strange
Richard C
RC
Stucker
Isabelle
I
Sugimura
Haruhiko
H
Garte
Seymour
S
Gaspari
Laura
L
Taioli
Emanuela
E
D000367:Age Factors; D016022:Case-Control Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics; D044469:Racial Groups / Q000235:genetics; D012307:Risk Factors; D012727:Sex Characteristics; D012907:Smoking; D013997:Time Factors
D019363:Cytochrome P-450 CYP1A1