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Risk of non-small cell lung cancer and the cytochrome P4501A1 Ile462Val polymorphism
Jill Everland Larsen1, Maree Louise Colosimo, Ian Anthony Yang
1Department of Thoracic Medicine, The Prince Charles Hospital, Brisbane, Australia. jill_e_larsen@health.qld.gov.au
Objective:
The Ile462Val substitution in the cytochrome P450 1A1 gene (CYP1A1) results in increased enzymatic activity. Preliminary data suggesting a link between this polymorphism and lung cancer risk in Caucasians are inconsistent, reflecting small sample sizes and the relatively low frequency of the variant.
Methods:
The data set consisted of 1050 primary non-small cell lung cancer cases and 581 controls, a large homogenous population designed specifically to address previous inconsistencies. Patients were genotyped using a PCR-RFLP technique.
Results:
Carriers of the valine allele, CYP1A1*2C, (Ile/Val or Val/Val genotypes) were significantly over-represented in non-small cell lung cancer compared to controls (OR=1.9; 95% CI=1.2-2.9; p=0.005) when adjusted for confounders, particularly in women (OR=4.6; 95% CI=1.7-12.4; p=0.003). The valine variant was statistically significantly over-represented in cases of lung cancer younger than the median age (64 years) (OR=2.5; 95% CI=1.3-4.8; p=0.005) and cases with less than the median cumulative tobacco-smoke exposure (46 pack-years) (OR=2.4; 95% CI=1.3-4.7; p=0.007).
Conclusions:
These new data establish an association between the CYP1A1 Ile462Val polymorphism and the risk of developing non-small cell lung cancer, especially among women.
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