Cancer Oral

J_ID: LARY Customer A_ID: 10-0521 Date: 13-May-10

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The Laryngoscope
C V 2010 The American Laryngological,

Rhinological and Otological Society, Inc.

Association Between DNA Repair Gene ATM Polymorphisms and Oral Cancer Susceptibility
AQ1 Da-Tian Bau, PhD; Chao-Hsiang Chang, XX; Ming-Hsui Tsai, XX; Chang-Fang Chiu, XX; Yung-An Tsou, XX; Rou-Fen Wang, XX; Chia-WenTsai, XX; Ru-Yin Tsai, PhD

Objectives/Hypothesis: The ataxia-telangiectasia mutated (ATM) is thought to play a major role in the caretaking of the overall genome stability, and its mutations have been implicated in human cancers. However, the role of ATM polymorphisms in oral carcinogenesis is largely unexplored. Thus, the polymorphic variants of ATM were first investigated for their associationwith oral cancer susceptibility. Study Design: In this hospital-based, case-control study, associations of seven ATM single nucleotide polymorphisms with oral cancer risk in a Taiwanese population were investigated. Methods: A total of 620 patients with oral cancer and 620 healthy controls were genotyped and analyzed by polymerase chain reaction and restriction fragment length polymorphism(PCR-RFLP) method. Results: There were significant differences between oral cancer and control groups in the distributions of their genotypes (P ¼ 3.71E-6) and allelic frequencies (P ¼ 5.09E-6) in the ATM rs189037 polymorphisms. In the other six polymorphisms, there was no differential distribution between both groups. There are synergistic joint interactions of ATM genotyping with smoking, alcoholdrinking, and betel quid chewing. Conclusions: The ATM rs189037 A allele is correlated with oral cancer susceptibility, and this polymorphism may be a useful marker for oral cancer prevention and early detection.
From the Departments of Otolaryngology ( M .- H . T., Y.- A . T.), Hematology Oncology (C.-F.C.), and Terry Fox Cancer Research Lab (D.-T.B., C.-H.C., M.-H.T., C.-F.C., Y.-A.T., R.-F.W.,C.-W.T., R.-Y.T.), China Medical University Hospital, and Graduate Institute of Chinese Medical Science (D.-T.B., C.-W.T.), China Medical University, Taichung, Taiwan. Editor’s Note: This Manuscript was accepted for publication April 20, 2010. This work was supported by research grants from the China Medical University and Hospital (DMR-99-045), Terry Fox Cancer Research Foundation, and the NationalScience Council (NSC 98-2320-B-039-010MY3). Send correspondence to Dr. Da-Tian Bau and Dr. Ru-Yin Tsai, Terry Fox Cancer Research Lab, Department of Medical Research, China Medical University Hospital, 2 Yuh-Der Road, Taichung, 404 Taiwan. E-mail: artbau1@yahoo.com.tw; datian@mail.cmuh.org.tw DOI: 10.1002/lary.21009

Key Words: ATM, polymorphism, oral cancer, carcinogenesis, betel quid. Level ofEvidence: N/A. Laryngoscope, 000:000–000, 2010

INTRODUCTION
Oral cancer, which is a commonly diagnosed cancer all over the world,1,2 has the highest incidence of all head and neck cancers in Taiwan.3 Three environmental factors—tobacco smoking, alcohol drinking, and betel quid chewing—are the major causes of oral cancer in Taiwan, while the genomic etiology of oral cancer is of great interestbut largely unknown. The human DNA repair system takes care of the genome and protects it from various insults caused by endogenous and environmental agents,4 and mutations or defects in the DNA repairing system are thought to be essential for tumorigenesis.5,6 Therefore, it is logical to suspect that some genetic variants of DNA repair genes might contribute to oral cancer pathogenesis. Carcinogensmay induce various types of DNA damage, including DNA adducts and single- and doublestrand breaks (DSBs). Among the different types of DNA damage and their associated DNA repair proteins, ataxia-telangiectasia mutated (ATM) plays a critical role in the recognition, signaling, and repairing of DNA DSBs.7 ATM is the product that mutated in autosomal recessive disease ataxia-telangiectasia (AT)...