Chi-Pin Lee1, Shang-Lun Chiang2,3, Chien-Hung Lee4, Yi-Shan Tsai4, Zhi-Hong Wang2, Chun-Hung Hua5, Yuan-Chien Chen6, Eing-Mei Tsai1, Ying-Chin Ko7,8,9. 1. Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. 2. Environment-Omics-Diseases Research Center, China Medical University Hospital, Taichung, Taiwan. 3. Department of Health Risk Management, College of Management, China Medical University, Taichung, Taiwan. 4. Department of Public Health, College of Health Science, Kaohsiung Medical University, Kaohsiung, Taiwan. 5. Department of Otolaryngology, China Medical University Hospital, Taichung, Taiwan. 6. Department of Dentistry, China Medical University Hospital, Taichung, Taiwan. 7. Environment-Omics-Diseases Research Center, China Medical University Hospital, Taichung, Taiwan. ycko@mail.cmu.edu.tw. 8. Graduate Institute of Clinical Medical Science, College of Medicine, China Medical University, Taichung, Taiwan. ycko@mail.cmu.edu.tw. 9. , 2 Yude Road, Taichung, 40447, Taiwan. ycko@mail.cmu.edu.tw.
Abstract
OBJECTIVES: The expression levels of two DNA repair genes (CHAF1A and CHAF1B) and a chromosome segregation gene (AURKA) were susceptible to arecoline exposure, a major alkaloid of areca nut. We hypothesize that genetic variants of these genes might also be implicated in the risk of oral cancer and could be modified by substance use of betel quid or alcohol and cigarettes. MATERIAL AND METHODS: A case-control study, which included 507 patients with oral cancer and 717 matched controls, was performed in order to evaluate the cancer susceptibility by the tagging single-nucleotide polymorphisms (tagSNPs) in AURKA, CHAF1A, and CHAF1B using a genotyping assay and gene-environment interaction analysis. RESULTS: The Phe31Ile polymorphism (rs2273535, T91A) of AURKA was significantly associated with an increased risk of oral cancer (odds ratio (OR) = 2.1, 95% confidence interval (CI) 1.2-3.5). The gene dosage of the 91A allele also showed a significant trend in risk of oral cancer (P = 0.008). Furthermore, we found the AURKA 91AA homozygote was modifiable by substance use of alcohol, betel quid, and cigarettes (ABC), leading to increased risk of oral cancer in an additive or a multiplicative model (combined effect indexes = 1.2-4.0 and 1.5-2.2, respectively). However, no association was observed between the genetic variants of CHAF1A or CHAF1B and oral cancer risk in the study. CONCLUSION: These findings reveal the functional Phe31Ile polymorphism tagSNP of AURKA may be a strong susceptibility gene in ABC-related oral cancer occurrence. CLINICAL RELEVANCE: The results of this betel-related oral cancer study provide the evidence of environment-gene interaction for early prediction and molecular diagnosis.
OBJECTIVES: The expression levels of two DNA repair genes (CHAF1A and CHAF1B) and a chromosome segregation gene (AURKA) were susceptible to arecoline exposure, a major alkaloid of areca nut. We hypothesize that genetic variants of these genes might also be implicated in the risk of oral cancer and could be modified by substance use of betel quid or alcohol and cigarettes. MATERIAL AND METHODS: A case-control study, which included 507 patients with oral cancer and 717 matched controls, was performed in order to evaluate the cancer susceptibility by the tagging single-nucleotide polymorphisms (tagSNPs) in AURKA, CHAF1A, and CHAF1B using a genotyping assay and gene-environment interaction analysis. RESULTS: The Phe31Ile polymorphism (rs2273535, T91A) of AURKA was significantly associated with an increased risk of oral cancer (odds ratio (OR) = 2.1, 95% confidence interval (CI) 1.2-3.5). The gene dosage of the 91A allele also showed a significant trend in risk of oral cancer (P = 0.008). Furthermore, we found the AURKA 91AA homozygote was modifiable by substance use of alcohol, betel quid, and cigarettes (ABC), leading to increased risk of oral cancer in an additive or a multiplicative model (combined effect indexes = 1.2-4.0 and 1.5-2.2, respectively). However, no association was observed between the genetic variants of CHAF1A or CHAF1B and oral cancer risk in the study. CONCLUSION: These findings reveal the functional Phe31Ile polymorphism tagSNP of AURKA may be a strong susceptibility gene in ABC-related oral cancer occurrence. CLINICAL RELEVANCE: The results of this betel-related oral cancer study provide the evidence of environment-gene interaction for early prediction and molecular diagnosis.
Authors: Elisabeth Feik; Andreas Baierl; Stephan Madersbacher; Georg Schatzl; Agnes Maj-Hes; Richard Berges; Michael Micksche; Andrea Gsur Journal: Cancer Causes Control Date: 2008-09-19 Impact factor: 2.506
Authors: Tuija Hienonen; Reijo Salovaara; Jukka-Pekka Mecklin; Heikki Järvinen; Auli Karhu; Lauri A Aaltonen Journal: Int J Cancer Date: 2006-01-15 Impact factor: 7.396
Authors: Amanda Ewart-Toland; Qi Dai; Yu-Tang Gao; Hiroki Nagase; Malcolm G Dunlop; Susan M Farrington; Rebecca A Barnetson; Hoda Anton-Culver; David Peel; Argyrios Ziogas; Dongxin Lin; Xiaoping Miao; Tong Sun; Elaine A Ostrander; Janet L Stanford; Mariela Langlois; June M Chan; Jinwei Yuan; Curtis C Harris; Elise D Bowman; Gary L Clayman; Scott M Lippman; J Jack Lee; Wei Zheng; Allan Balmain Journal: Carcinogenesis Date: 2005-03-31 Impact factor: 4.944