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Cathepsin B SNPs elevate the pathological development of oral cancer and raise the susceptibility to carcinogen-mediated oral cancer

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Abstract

Oral cancer is causally associated with environmental carcinogens, and the susceptibility to carcinogen-mediated tumorigenesis is proposed to be genotype-dependent. Cathepsin B (CTSB) is a lysosomal cysteine protease and may serve as a candidate biomarker of oral cancer. The current study aimed to explore the influences of three single nucleotide polymorphisms (SNPs) in CTSB gene, combined with environmental carcinogens on the risk and clinicopathological development of oral cancer. Three SNPs of CTSB, CTSB C76G (rs12338), CTSB A4383C (rs13332), and CTSB A8422G (rs8898), from 444 male patients with oral cancer and 426 control participants (males not diagnosed with cancer) in Taiwan were analyzed. These three CTSB SNPs all exhibited insignificant (P > 0.05) effects on the risk of oral cancer. However, the risk for developing the poor clinical stage of moderately or poorly differentiated cells was significantly (P < 0.001) increased to 3.325-fold in patients with oral cancer carrying the polymorphic genotype of rs8898 compared to patients with the ancestral genotype. Additionally, while considering the exposure of environmental carcinogens, the presence of these three CTSB SNPs, combined with betel quid chewing [adjusted odds ratio (AOR) was 36.570, 21.772, and 43.962 for rs12338, rs13332, and rs8898, respectively] and/or tobacco use (AOR was 3.794, and 8.972 for rs12338 and rs13332, respectively), robustly elevated the susceptibility to oral cancer. These results suggest that the genetic polymorphism of CTSB A8422G (rs8898) was associated with a high risk for the clinicopathological development of oral cancer and CTSB gene polymorphisms may increase the susceptibility to environmental carcinogens-mediated oral cancer.

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Abbreviations

AOR:

Adjusted odds ratio

CI:

Confidence interval

CTSB:

Cathepsin B

OSCC:

Oral squamous cell carcinoma

PCR:

Polymerase chain reaction

SNP:

Single nucleotide polymorphisms

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Acknowledgments

This study was supported by a research grant from National Science Council, Taiwan (NSC 100-2314-B-040 -004 and NSC 101-2314-B-371 -002 -MY3).

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Authors and Affiliations

  1. Graduate Institute of Applied Science of Living, Tainan University of Technology, 529 Zhongzheng Rd., Yongkang, Tainan, 71002, Taiwan

    Chia-Jui Weng

  2. Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Shih-Chi Su

  3. Institute of Oral Science, Chung Shan Medical University, Taichung, Taiwan

    Chiao-Wen Lin

  4. Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan

    Chiung-Man Tsai & Shun-Fa Yang

  5. Hualien Hospital, Department of Health, Executive Yuan, Hualien City, Hualien County, Taiwan

    Chiung-Man Tsai

  6. Department of Otorhinolaryngology-Head and Neck Surgery, Changhua Christian Hospital, Changhua, Taiwan

    Mu-Kuan Chen

  7. Department of Medical Research, Chung Shan Medical University Hospital, No.110, Sec.1, Jianguo N. Rd, Taichung, 40256, Taiwan

    Shun-Fa Yang

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  1. Mu-Kuan Chen
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  2. Shih-Chi Su
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  3. Chiao-Wen Lin
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Correspondence to Shun-Fa Yang or Chia-Jui Weng.

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Chen, MK., Su, SC., Lin, CW. et al. Cathepsin B SNPs elevate the pathological development of oral cancer and raise the susceptibility to carcinogen-mediated oral cancer. Hum Genet 131, 1861–1868 (2012). https://doi.org/10.1007/s00439-012-1211-1

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  • DOI: https://doi.org/10.1007/s00439-012-1211-1

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