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Functional variant of KLOTHO: a breast cancer risk modifier among BRCA1 mutation carriers of Ashkenazi origin
Oncogene, 10/14/09

Wolf I et al. – Studies in breast cancer cells showed reduced growth inhibitory activity and reduced secretion of klotho F352V compared with wild-type klotho. These data suggest KL-VS as a breast and ovarian cancer risk modifier among BRCA1 mutation carriers. If validated in additional cohorts, the presence of KL-VS may serve as a predictor of cancer risk among BRCA1 mutation carriers.

Methods

Examined the association between KL-VS and cancer risk among 1115 Ashkenazi Jewish women
236 non-carriers, 631 BRCA1 (185delAG, 5382insC) carriers and 248 BRCA2 (6174delT) carriers

Results

Among BRCA1 carriers, heterozygosity for KL-VS allele associated with increased breast and ovarian cancer risk (hazard ratio 1.40, 95% confidence intervals 1.08–1.83) and younger age at breast cancer diagnosis (median age 48 vs 43)
KLOTHO and BRCA2 located on 13q12, and identified linkage disequilibrium between KL-VS and BRCA2 6174delT mutation
Studies in breast cancer cells showed reduced growth inhibitory activity and reduced secretion of klotho F352V compared with wild-type klotho

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