Enhanced Risk of Lung and Prostate Adenocarcinoma in African-American Smokers Carrying a Novel Cypiai Gene Polymorphism

Abstract

The CYPlA1 gene codes for aromatic hydrocarbon hydroxlase (AHH), a critical enzyme in the metabolism of carcinogenic polycyclic aromatic hydrocarbons. Polymorphisms in this gene have been implicated in aberrant gene function, and in increased risk of cancer from exposure to hydrocarbons such as those found in tobacco smoke. We have discovered a novel restriction polymorphism (“AA RFLP”) in this gene that is found only in people of African descent. African Americans suffer a disproportionate high incidence of lung and prostate cancer. This is not due to increased smoking, but may be related to either environmental or genetic factors. We have examined the possibility that the African American specific CYPlA1 RFLP may be associated with higher risk for tobacco related carcinogenesis. The incidence of the AA polymorphism in the healthy African-American population was 14.5%. In African-Americans with adenocarcinoma of the lung the incidence of the polymorphism was doubled. We observed no difference between cases and controls in the incidence of the exon 7 polymorphism of the CYPlA1 gene. A preliminary study was conducted on tissue cks from African-American prostate cancer patients. Overall, the AA RFLP was not significantly associated with prostate cancer; however, subjects who both smoke and carry the AA RFLP have significantly higher risk of prostate cancer than subjects who either smoke alone, or carry the AA RFLP alone. This study represents a model for investigation of gene-environment interactions related to PAH induced carcinogenesis.

Key words::

• genetic susceptibility
• environment
• tobacco metabolism
• gene-environment interaction