Abstract
BackgroundA rural region in south-west Spain has one of the highest lung cancer incidence rates of the country, as revealed by a previous epidemiological 10-year follow-up study. The present work was undertaken to ascertain the role of CYP1A1 gene polymorphisms and their interaction with tobacco smoking in the development of the disease in this location.MethodsOne-hundred-and-three cases of lung cancer and 265 controls participated in the study. The participants were screened for the presence of four CYP1A1 polymorphisms, namely MspI, Ile462Val, T3205C, and Thr461Asn. Lung cancer risk was estimated as odds ratios (OR) and 95% confidence intervals (CI) using unconditional logistic regression models adjusting for age, sex, and smoking.ResultsThe distribution of the variant CYP1A1 alleles was different from that described for other Caucasian populations, with CYP1A1*2A showing an uncommonly high frequency (p < 0.01). The CYP1A1*2B allele (carrying MspI and Ile462Val mutations) was strongly associated with high lung cancer risk (OR = 4.59, CI:1.4-12.6, p <0.01). The Ile462Val polymorphism was also shown to increase the risk for the disease (OR = 4.51, CI:1.8-11.9; p <0.01) and particularly for squamous-cell (OR = 5.01; CI: 1.6-14.3, p < 0.01) and small-cell lung carcinoma (SCLC) (OR = 6.97, CI: 1.2-81.3; p = 0.04). Moreover, the Thr461Asn polymorphism was found to be associated with SCLC in a Caucasian population for the first time to our knowledge (OR = 8.33, CI: 1.3-15.2, p = 0.04).ConclusionThe results suggest that CYP1A1 polymorphisms contribute to increase lung cancer susceptibility in an area with an uncommon high incidence rate.
Highlights
A rural region in south-west Spain has one of the highest lung cancer incidence rates of the country, as revealed by a previous epidemiological 10-year follow-up study
This study was designed to determine whether genetic polymorphisms in the CYP1A1 gene, an activator of carcinogens present in tobacco smoke, could play a role in the extremely high lung cancer incidence rate observed in a rural region of Southern Spain
Unlike our findings for the Ile462Val and Thr461Asn polymorphisms, the results showed no association of the MspI polymorphism (CYP1A1*2A allele) with lung cancer, which is consistent with earlier reports in Caucasians [40,41,42]
Summary
A rural region in south-west Spain has one of the highest lung cancer incidence rates of the country, as revealed by a previous epidemiological 10-year follow-up study. A group of oncologists working at the Merida hospital, which is located in an agricultural region situated in south-west Spain, started to notice the unusually high number of lung cancer patients being diagnosed. This prompted the creation of a local lung cancer registry in accordance with the guidelines issued by the International Agency for Research on Cancer (IARC) and the International Association of Cancer Registries (IACR). Both the formation of these PAH-DNA adducts and CYP1A1 expression in human lung tissue are highly variable [10,11,12,13], possibly due to differing exposure to environmental factors and to genetic polymorphisms affecting the CYP1A1 gene locus
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