Surfactant protein B gene variations and susceptibility to lung cancer in chromate workers

Authors

  • Ashraf A. Ewis MD, PhD,

    Corresponding author
    1. Single-Molecule Bioanalysis Laboratory, National Institute of Advanced Industrial Science and Technology (AIST), Takamatsu, Japan
    2. Department of Public Health and Occupational Medicine, Faculty of Medicine, El-Minia University, Egypt
    • Lecturer of Occupational Medicine, Department of Public Health and Occupational Medicine, Faculty of Medicine, El-Minia University, 61111 El-Minia, Egypt.
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  • Kazuya Kondo MD, PhD,

    1. Department of second Surgery, School of Medicine, Tokushima University, Japan
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  • Fuquan Dang PhD,

    1. Single-Molecule Bioanalysis Laboratory, National Institute of Advanced Industrial Science and Technology (AIST), Takamatsu, Japan
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  • Yutaka Nakahori MD, PhD,

    1. Department of Human Genetics and Public Health, School of Medicine, University of Tokushima, Tokushima, Japan
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  • Yasuo Shinohara PhD,

    1. Division of Gene Expression, Institute for Genome Research, The University of Tokushima, Tokushima, Japan
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  • Mitsuru Ishikawa PhD,

    1. Single-Molecule Bioanalysis Laboratory, National Institute of Advanced Industrial Science and Technology (AIST), Takamatsu, Japan
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  • Yoshinobu Baba PhD

    1. Single-Molecule Bioanalysis Laboratory, National Institute of Advanced Industrial Science and Technology (AIST), Takamatsu, Japan
    2. Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, The University of Tokushima, CREST, JST, Shomachi, Tokushima, Japan
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Abstract

Background

Hexavalent chromium has been extensively investigated regarding its mutagenicity and carcinogenicity; however, its mechanism for initiating and enhancing the development of lung cancer is still obscure. Biomarkers of exposure, effect or susceptibility are required for risk assessment and for epidemiologic research studies especially in occupational settings. Since the surfactant protein system (SP) is very important for normal lung function and for mediating local airway conditions and in the clearance of the upper respiratory tract from the occupational and environmental dusts, we hypothesize that SP genes may represent good candidates to study susceptibility for lung cancer.

Methods

Using PCR genotyping methods with gel electrophoresis and confirmation of results with precise DNA fragment size measurement on microchip electrophoresis, we analyzed SP-B intron-4 polymorphism in 230 subjects who were classified into groups; chromate-related lung cancer, control chromate workers who had not developed lung cancer, control individuals with non chromate-related adenocarcinoma or squamous cell carcinoma of the lungs, or healthy Japanese control individuals.

Results

Our results indicated that the SP-B variants (deletion/insertion) were significantly overrepresented (61.3%) in the chromate-related lung cancer group than other groups (X2 = 47.6; DF = 4, P = 0.0001). There was a significant difference between the chromate lung cancer group and both of the control groups, healthy individuals and chromate workers who did not develop lung cancer, showing odds ratios (OR) with 95% confidence intervals (CI) of 21.9 (7.3–65.7) and 19.0 (3.78–95.4), respectively. Compared with 46 non chromate-related SCC of the lung, the SP-B variants were significantly overrepresented in the chromate-related SCC (18/28; 64.3%) than the non-chromate SCC (11/46; 23.9%) of the lung samples (X2 = 10.27, P = 0.01), OR with 95% CI is 5.73 (2.05–16.01).

Conclusion

These findings indicate a very strong association of the SP-B intron-4 variants with mechanisms that may enhance lung cancer susceptibility, especially in workers who are employed in chromate industry. Moreover, confirmation of such results may help to suggest adding the SP-B intron-4 typing to be one of the screening tests of the pre-placement medical examination to confirm that the worker has no variations of the SP-B gene before being engaged in a chromium-related industry, with the intention of providing proper medical counseling. Am. J. Ind. Med. 49:367–373, 2006. © 2006 Wiley-Liss, Inc.

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