Hypopharyngeal cancer risk in Japanese: Genetic polymorphisms related to the metabolism of alcohol- and tobacco-associated carcinogens
Yukashi Yamashita1, Taro Ikegami1, Mikio Suzuki1, Hitoshi Hirakawa1, Hiroyuki Maeda1, Satoshi Yamada2, Zeyi Deng3, Shunsuke Kondo1, Hidetoshi Kinjyo1, Asanori Kiyuna1, Shinya Agena1, Takayuki Uehara1, Akira Ganaha1
1 Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan
2 Department of Pharmacy, University Hospital, University of the Ryukyus, Okinawa, Japan
3 Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan; Department of Otorhinolaryngology, Head and Neck Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China
Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, University of the Ryukyus, Okinawa 903-0215
Source of Support: None, Conflict of Interest: None
Background: Several studies have investigated hypopharyngeal cancer (HC) risk in combination with xenobiotic metabolism-related genetic polymorphisms and the burden of alcohol consumption and smoking in European countries but not in East Asian countries.
Patients and Methods: This hospital-based case–control study involved 61 male patients with HC and 71 male cancer-free controls. Information on age, body mass index, and alcohol and cigarette consumption was obtained from medical records, a self-completion questionnaire, and a thorough interview by an otolaryngologist. Alcohol dehydrogenase 1B (ADH1B), aldehyde dehydrogenase 2 (ALDH2), cytochrome P450 A1 (CYP1A1) MspI, CYP1A1 Ile462Val, glutathione S-transferase (GST) M1, GSTT1, and GSTP1 gene polymorphisms were determined by polymerase chain reaction-based methods. Univariate and multivariate analyses were performed by adjustment for age by the Mantel–Haenszel method.
Results: The burden of alcohol and cigarette consumption significantly increased the risk of HC and showed a synergistic effect. ADH1B*1/*1 (odds ratio [OR] 7.34) and ALDH2 *1/*2 (OR 13.22) were significant risk factors for HC. Individuals with ADH1B*1/*1 or ALDH2 *1/*2 who consumed alcohol were more susceptible to HC. However, polymorphisms of CYP1A1 gene and GSTs were not significant cancer risk factors in patients with HC.
Conclusions: ADH1B*1/*1 and ALDH2 *1/*2 were significant risk factors for HC, while polymorphism of CYP1A1 gene and GSTs was not a significant risk factor for HC. These polymorphisms determined the effects of alcohol and cigarette smoke in addition to burden of alcohol and cigarettes intake on the risk of HC.