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JNCI Journal of the National Cancer Institute 2004 96(24):1866-1869; doi:10.1093/jnci/dji001
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© 2004 Oxford University Press

BRIEF COMMUNICATION

Association of a Common Variant of the CASP8 Gene With Reduced Risk of Breast Cancer

Gordon MacPherson, Catherine S. Healey, M. Dawn Teare, Sabapathy P. Balasubramanian, Malcolm W. R. Reed, Paul D. P. Pharoah, Bruce A. J. Ponder, Mark Meuth, Nitai P. Bhattacharyya, Angela Cox

Affiliations of authors: Division of Genomic Medicine, University of Sheffield Medical School, Sheffield, U.K. (GM, MDT, MM, AC); Department of Oncology, University of Cambridge, Strangeways Research Laboratory, Cambridge, U.K. (CSH, PDPP, BAJP); Academic Surgical Oncology Unit, University of Sheffield Medical School, Sheffield, U.K. (SPB, MWRR); Saha Institute of Nuclear Physics, Calcutta, India (NPB)

Correspondence to: Angela Cox, PhD, Institute for Cancer Studies, University of Sheffield Medical School, Beech Hill Rd., Sheffield S10 2RX, U.K. (e-mail: a.cox{at}shef.ac.uk)

Apoptosis, or programmed cell death, is perturbed in many cancers. We tested the hypothesis that coding polymorphisms of the death receptor 4 (DR4), caspase-8 (CASP8), and caspase-10 (CASP10) genes might act as low-penetrance breast cancer genes. Single-nucleotide polymorphisms (SNPs) of these genes were genotyped in a series of 999 breast cancer case patients and 996 control subjects from Sheffield, U.K., and in a second, independent U.K. population of 2192 case patients and 2262 control subjects from East Anglia. In the Sheffield study, the rare H allele of CASP8, D302H, was associated with a reduced risk of breast cancer in a dose-dependent manner (Ptrend = .007). Furthermore, the CASP8 D302H association, but not that of the other CASP8 SNPs examined (T21914C, G50121A, and G50358A), was replicated in the East Anglian study. The combined adjusted odds ratios for breast cancer were 0.83 (95% confidence interval [CI] = 0.74 to 0.94) for the DH heterozygote and 0.58 (95% CI = 0.39 to 0.88) for the HH homozygote (Ptrend = .0002, adjusted for study). The reproducible, dose-dependent association of CASP8 D302H with breast cancer indicates the potential importance of inherited variation in the apoptosis pathway in breast cancer susceptibility.


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Correspondence about this Article

Re: Association of a Common Variant of the CASP8 Gene With Reduced Risk of Breast Cancer
Bernd Frank, Justo Lorenzo Bermejo, Kari Hemminki, Rüdiger Klaes, Peter Bugert, Barbara Wappenschmidt, Rita K. Schmutzler, and Barbara Burwinkel
J Natl Cancer Inst 2005 97: 1012. [Extract] [Full Text] [PDF]



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