Genetic association study of CYP1A1 polymorphisms identifies risk haplotypes in nonsmall cell lung cancer.
Lung cancer remains a leading cause of disease globally, with smoking being the largest single cause. Phase I enzymes, including cytochrome P(450), family 1, subfamily A, polypeptide 1 (CYP1A1), are involved in the activation of carcinogens, such as polycyclic aromatic hydrocarbons, to reactive intermediates that are capable of binding covalently to DNA to form DNA adducts, potentially initiating the carcinogenic process. The aim of the present study was to investigate the association of CYP1A1 gene polymorphisms and haplotypes with lung cancer risk. A case-control study was carried out on 1,040 nonsmall cell lung cancer (NSCLC) cases and 784 controls to investigate three CYP1A1 variants, CYP1A1*2A (rs4646903; thymidine to cytosine substitution at nucleotide 3801 (3801T>C)), CYP1A1*2C (rs1048943; 2455A>G; substitution of isoleucine 462 with valine (exon 7)) and CYP1A1*4 (rs1799814; 2453C>A; substitution of threonine 461 with asparagine (exon 7)) using PCR restriction fragment length polymorphism methods. The CYP1A1*2A and CYP1A1*2C variants were significantly over-represented in NSCLC cases compared with controls, whereas the CYP1A1*4 variant was under-represented. CYP1A1 haplotypes (in allele order CYP1A1*4, CYP1A1*2C, CYP1A1*2A) CGC and CGT were associated with an increased risk of lung cancer, whereas AAT was associated with decreased lung cancer risk in this population. The present study has identified risk haplotypes for CYP1A1 in NSCLC and confirmed that CYP1A1 polymorphisms are a minor risk factor for NSCLC.
Wright
C M
CM
Dept of Thoracic Medicine, Room 2, Level 1 Clinical Sciences Building, The Prince Charles Hospital, Chermside, QLD, Australia. c.wright@uq.edu.au
Larsen
J E
JE
Colosimo
M L
ML
Barr
J J
JJ
Chen
L
L
McLachlan
R E
RE
Yang
I A
IA
Bowman
R V
RV
Fong
K M
KM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D016022:Case-Control Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors; D055815:Young Adult
D019363:Cytochrome P-450 CYP1A1