Lung cancer susceptibility gene and molecular pathology of lung cancer.

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Okinawa, a group of islands which lie between the East China Sea and the Pacific Ocean, 2000 km south of the Japanese main islands, have a different profile of diseases, ethnicities and cultures than the rest of Japan. We examined an Ile462Val polymorphism (CYP1A1**2 allele) of cytochrome P450 IA1 (CypIA1) in a hospital based case-control study of lung cancer patients in Okinawa to ascertain the associatin of this variant with lung cancer. In addition, the distribution of this genotype was studied in populations from different areas of Japan, including Tokyo and Iwate (northern part of Japan), as well as in Chinese in the Jiangsu province and an Australian Caucasian group. Genotype frequency in controls was not significantly diffeerent from area to area in Japan. In Okinawa, however, the genotype encoding Val/Val was associated with a significantly higher risk of lung cancer (odds ratio 3.32, P = 0.013), especially squamous cell carcinoma and small cell carcinoma (odds ratios are 4.85 and 9.35 respectively). The Val-encoding allele was less frequent in Chinese and rare in Australian Caucasians. The present study thus gives support to the value of the CypIA1 Ile462Val polymorphism as a practical high risk marker of lung cancer in populations, especially those in South-east Asia in which this variant is more common.