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


METHODS
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.


RESULTS
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).


CONCLUSIONS
This is the first study to demonstrate a significant association between the homozygous UGT1A1*28 genotype and lung cancer.
Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, Kyoto, 606-8507, Japan.
Yoshitaka
Y
Nishikawa
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.
Masashi
M
Kanai
Center for Genomic Medicine, Graduate School of Medicine, Kyoto University, 53 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.|Department of Human Genetics, McGill University, 740 Dr. Penfield Avenue, Montréal, H3A 0G1, Canada.
Maiko
M
Narahara
Department of Clinical System Onco-Informatics, Graduate School of Medicine, Kyoto University, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.
Akiko
A
Tamon
Department of Clinical System Onco-Informatics, Graduate School of Medicine, Kyoto University, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.|Center for Medical Education, Graduate School of Medicine, Kyoto University, Konoemachi Med Bldg E, Sakyo-ku, Kyoto, 606-8501, Japan.
J B
JB
Brown
Department of Clinical System Onco-Informatics, Graduate School of Medicine, Kyoto University, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.|RIKEN Advanced Institute for Computational Science, 7-1-26 Minatojima-minami-machi, Chuo-ku, Kobe, Hyogo, 650-0047, Japan.
Kei
K
Taneishi
Department of Clinical System Onco-Informatics, Graduate School of Medicine, Kyoto University, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.
Masahiko
M
Nakatsui
Division of Medical Information Technology and Administration Planning, Kyoto University Hospital, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.
Kazuya
K
Okamoto
Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, Kyoto, 606-8507, Japan.
Yu
Y
Uneno
Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, Kyoto, 606-8507, Japan.
Daisuke
D
Yamaguchi
Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.
Teruko
T
Tomono
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.
Yukiko
Y
Mori
Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, Kyoto, 606-8507, Japan.
Shigemi
S
Matsumoto
Department of Clinical System Onco-Informatics, Graduate School of Medicine, Kyoto University, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.|RIKEN Advanced Institute for Computational Science, 7-1-26 Minatojima-minami-machi, Chuo-ku, Kobe, Hyogo, 650-0047, Japan.
Yasushi
Y
Okuno
Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, Kyoto, 606-8507, Japan. mmuto@kuhp.kyoto-u.ac.jp.
Manabu
M
Muto
D000230:Adenocarcinoma / Q000453:epidemiology / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008175:Lung Neoplasms / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D011446:Prospective Studies; D055752:Small Cell Lung Carcinoma / Q000453:epidemiology / Q000235:genetics*; D012907:Smoking; D055815:Young Adult; D000099148:UGT1A1 Enzyme
D014408:Biomarkers, Tumor; D014453:Glucuronosyltransferase; D000099148:UGT1A1 Enzyme
Lung cancer; Smoking; UGT1A1