Association between UGT1A1*28*28 genotype and lung cancer in the Japanese population

Yoshitaka Nishikawa, Masashi Kanai, Maiko Narahara, Akiko Tamon, J. B. Brown, Kei Taneishi, Masahiko Nakatsui, Kazuya Okamoto, Yu Uneno, Daisuke Yamaguchi, Teruko Tomono, Yukiko Mori, Shigemi Matsumoto, Yasushi Okuno, Manabu Muto

Lung cancer is the leading cause of cancer death and is closely linked to tobacco smoking. Genetic polymorphisms in genes that encode enzymes involved in metabolizing tobacco carcinogens could affect an individual's risk for lung cancer. While polymorphism of UDP-glucuronosyltransferase1A1 (UGT1A1) is involved in detoxification of benzo(a)pyrene-7,8-dihydrodiol(-), a major tobacco carcinogen, the association between UGT1A1 genotype and lung cancer has not been examined. We retrieved the clinical data of 5,285 patients who underwent systemic chemotherapy at Kyoto University Hospital. A total of 765 patients (194 lung cancer patients and 671 patients with other malignancies) with UGT1A1 genotyping data were included in this analysis. We used logistic regression with recessive, dominant, and additive models to identify differences in genotype frequencies between lung cancer and other malignancies. In the recessive model, UGT1A1*28*28 genotype was significantly associated with lung cancer compared to other malignancies (odds ratio 5.3, P = 0.0083). Among lung cancer patients with a smoking history, squamous cell carcinoma was significantly predominant in patients with UGT1A1*28*28 compared to those with other UGT1A1 genotypes (P = 0.024). This is the first study to demonstrate a significant association between the homozygous UGT1A1*28 genotype and lung cancer.