Lung cancer susceptibility gene and molecular pathology of lung cancer.

冲绳是位于东中国海和太平洋之间的一群岛屿，位于日本主要岛屿以南2000公里处，其疾病、种族和文化特征与日本其他地区不同。我们在冲绳一项以医院为基础的病例对照研究中检测了细胞色素P450 IA1(CypIA1)的Ile462Val多态(CYP1A1**2等位基因)，以确定该变异与肺癌的相关性。此外，还研究了该基因在日本不同地区的人群中的分布，包括东京和岩手县(日本北部)，以及江苏省的中国人和一个澳大利亚高加索人群体。在日本，对照组的基因频率在不同地区之间没有显著差异。然而，在冲绳，Val/Val编码基因与患肺癌的风险显著增加(优势比3.32，P=0.013)，特别是鳞癌和小细胞癌(优势比分别为4.85和9.35)。编码Val的等位基因在中国人中较少出现，在澳大利亚高加索人中很少见。因此，本研究支持了CypIA1 Ile462Val多态在人群中作为肺癌实用高危标记物的价值，特别是在该变异更常见的东南亚地区。

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.