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AURKA Phe31Ile polymorphism interacted with use of alcohol, betel quid, and cigarettes at multiplicative risk of oral cancer occurrence

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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.

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Acknowledgments

This work was supported by grants from the Ministry of Science and Technology (MOST-103-2314-B-039-003) and health and welfare surcharge of tobacco productions, China Medical University Hospital Cancer Research Center of Excellence (MOHW104-TDU-B-212-124-002, Taiwan), and Grant DMR 103-113 from China Medical University Hospital, Taichung, Taiwan.

Conflict of interest

The authors declare no conflict of interest.

Author information

Authors and Affiliations

  1. Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Chi-Pin Lee & Eing-Mei Tsai

  2. Environment-Omics-Diseases Research Center, China Medical University Hospital, Taichung, Taiwan

    Shang-Lun Chiang, Zhi-Hong Wang & Ying-Chin Ko

  3. Department of Public Health, College of Health Science, Kaohsiung Medical University, Kaohsiung, Taiwan

    Chien-Hung Lee & Yi-Shan Tsai

  4. Department of Otolaryngology, China Medical University Hospital, Taichung, Taiwan

    Chun-Hung Hua

  5. Department of Dentistry, China Medical University Hospital, Taichung, Taiwan

    Yuan-Chien Chen

  6. Graduate Institute of Clinical Medical Science, College of Medicine, China Medical University, Taichung, Taiwan

    Ying-Chin Ko

  7. Department of Health Risk Management, College of Management, China Medical University, Taichung, Taiwan

    Shang-Lun Chiang

  8. 2 Yude Road, Taichung, 40447, Taiwan

    Ying-Chin Ko

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  1. Chi-Pin Lee
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Lee, CP., Chiang, SL., Lee, CH. et al. AURKA Phe31Ile polymorphism interacted with use of alcohol, betel quid, and cigarettes at multiplicative risk of oral cancer occurrence. Clin Oral Invest 19, 1825–1832 (2015). https://doi.org/10.1007/s00784-015-1432-5

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  • DOI: https://doi.org/10.1007/s00784-015-1432-5

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