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Bladder cancer SNP panel predicts susceptibility and survival

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Abstract

Bladder cancer is the fourth most common malignancy in men and the eighth most common in women in western countries. Single nucleotide polymorphisms (SNPs) in genes that regulate telomere maintenance, mitosis, inflammation, and apoptosis have not been assessed extensively for this disease. Using a population-based study with 832 bladder cancer cases and 1,191 controls, we assessed genetic variation in relation to cancer susceptibility or survival. Findings included an increased risk associated with variants in the methyl-metabolism gene, MTHFD2 (OR 1.7 95% CI 1.3–2.3), the telomerase TEP1 (OR 1.8 95% CI 1.2–2.6) and decreased risk associated with the inflammatory response gene variant IL8RB (OR 0.6 95% CI 0.5–0.9) compared to wild-type. Shorter survival was associated with apoptotic gene variants, including CASP9 (HR 1.8 95% CI 1.1–3.0). Variants in the detoxification gene EPHX1 experienced longer survival (HR 0.4 (95% CI 0.2–0.8). These genes can now be assessed in multiple study populations to identify and validate SNPs appropriate for clinical use.

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Acknowledgments

This publication was funded in part by grant numbers CA102327, CA121382, CA099500, CA82354, CA57494, CA078609, ES00002, P42 ES05947, RR018787, LM009012 and ES007373 from the National Cancer Institute, NIH and from the National Institute of Environmental Health Sciences, NIH.

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Authors and Affiliations

  1. Section of Biostatistics and Epidemiology, Department of Community and Family Medicine, Dartmouth Medical School, 7927 Rubin 860, One Medical Center Drive, Lebanon, NH, 03756, USA

    Angeline S. Andrew, Jiang Gui, Rebecca A. Mason, Elaine V. Morlock, Jason H. Moore & Margaret R. Karagas

  2. Department of Pathology, Dartmouth Medical School, Lebanon, NH, 03756, USA

    Alan R. Schned

  3. Department of Electrical, Computer and Systems Engineering, Rensselaer Polytechnic Institute, Troy, NY, 12180, USA

    Arthur C. Sanderson

  4. Departments of Community Health, and of Pathology and Laboratory Medicine, Brown University, Providence, RI, 02912, USA

    Karl T. Kelsey & Carmen J. Marsit

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  1. Angeline S. Andrew
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  2. Jiang Gui
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  3. Arthur C. Sanderson
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  4. Rebecca A. Mason
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  5. Elaine V. Morlock
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  6. Alan R. Schned
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  9. Jason H. Moore
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  10. Margaret R. Karagas
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Correspondence to Angeline S. Andrew.

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Andrew, A.S., Gui, J., Sanderson, A.C. et al. Bladder cancer SNP panel predicts susceptibility and survival. Hum Genet 125, 527–539 (2009). https://doi.org/10.1007/s00439-009-0645-6

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