ASSOCIATION OF ILE462VAL (EXON 7) POLYMORPHISM OF CYTOCHROME-P450 IA1WITH LUNG-CANCER IN THE ASIAN POPULATION - FURTHER EVIDENCE FROM A CASE-CONTROL STUDY IN OKINAWA

Okinawa, a group of islands that lie between the East China Sea and th e Pacific Ocean, 2000 km south of the Japanese main islands, has a dif ferent profile of diseases, ethnicities, and cultures than does the re st of Japan. We examined an Ile462Val polymorphism (CYP1A12 allele) o f cytochrome P450 IA1 in a hospital-based case-control study of lung c ancer patients (247 cases and 185 controls) in Okinawa to ascertain th e association of this variant with lung cancer. In addition, the distr ibution of this genotype was studied in populations from different are as of Japan, including Tokyo (n = 69) and Iwate (northern part of Japa n; II = 81), as well as in a Chinese group from the Jiangsu province ( n = 39) and in an Australian Caucasian group (rt = 146), Genotype freq uency in controls was not significantly different from area to area in Japan. In Okinawa, however, the genotype encoding Val/Val was associa ted with a significantly higher risk of lung cancer (odds ratio = 3.32 , P = 0.013), especially of squamous cell carcinoma and small cell car cinoma (odds ratio = 4.85 and 9.35, respectively). The Val-encoding al lele was less frequent in the Chinese population and was rare in Austr alian Caucasians, Thus, this study gives support to the value of the c ytochrome P450 IA1 Ile462Val polymorphism as a practical high-risk mar ker of lung cancer in populations, especially those in southeast Asia, in which this variant is more common.