Nishikawa Yoshitaka, Kanai Masashi, Narahara Maiko, Tamon Akiko, Brown J B, Taneishi Kei, Nakatsui Masahiko, Okamoto Kazuya, Uneno Yu, Yamaguchi Daisuke, Tomono Teruko, Mori Yukiko, Matsumoto Shigemi, Okuno Yasushi, Muto Manabu
Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, Kyoto, 606-8507, Japan.
Department of Clinical Oncology, Pharmacogenomics, and Palliative Medicine, Graduate School of Medicine, Kyoto University, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.
Int J Clin Oncol. 2017 Apr;22(2):269-273. doi: 10.1007/s10147-016-1061-2. Epub 2016 Nov 10.
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, UGT1A12828 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 UGT1A12828 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.
肺癌是癌症死亡的主要原因，与吸烟密切相关。编码参与烟草致癌物代谢的酶的基因中的遗传多态性可能会影响个体患肺癌的风险。虽然尿苷二磷酸葡萄糖醛酸基转移酶1A1（UGT1A1）的多态性参与了主要烟草致癌物苯并（a）芘-7,8-二氢二醇（-）的解毒过程，但UGT1A1基因型与肺癌之间的关联尚未得到研究。
我们检索了京都大学医院5285例接受全身化疗患者的临床资料。本分析纳入了765例有UGT1A1基因分型数据的患者（194例肺癌患者和671例其他恶性肿瘤患者）。我们使用隐性、显性和加性模型的逻辑回归来确定肺癌和其他恶性肿瘤之间基因型频率的差异。
在隐性模型中，与其他恶性肿瘤相比，UGT1A12828基因型与肺癌显著相关（优势比5.3，P = 0.0083）。在有吸烟史的肺癌患者中，与其他UGT1A1基因型的患者相比，UGT1A2828患者的鳞状细胞癌明显占优势（P = 0.024）。
这是第一项证明纯合UGT1A1*28基因型与肺癌之间存在显著关联的研究。
