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Is multiple SNP testing in BRCA2 and BRCA1 female carriers ready for use in clinical practice? Results from a large Genetic Centre in the UK
Author(s) -
Ingham SL,
Warwick J,
Byers H,
Lalloo F,
Newman WG,
Evans DGR
Publication year - 2013
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.12035
Subject(s) - breast cancer , single nucleotide polymorphism , medicine , oncology , concordance , odds ratio , snp , genetic testing , allele , cancer , genetics , gynecology , genotype , biology , gene
BRCA1 and BRCA2 are major breast cancer susceptibility genes. Nineteen single nucleotide polymorphisms ( SNPs ) at 18 loci have been associated with breast cancer. We aimed to determine whether these predict breast cancer incidence in women with BRCA1 / BRCA2 mutations. BRCA1 /2 mutation carriers identified through the Manchester genetics centre between 1996 and 2011 were included. Using published odds ratios ( OR ) and risk allele frequencies, we calculated an overall breast cancer risk SNP score ( OBRS ) for each woman. The relationship between OBRS and age at breast cancer onset was investigated using the Cox proportional hazards model, and predictive ability assessed using Harrell's C concordance statistic. In BRCA1 mutation carriers we found no association between OBRS and age at breast cancer onset: OR for the lowest risk quintile compared to the highest was 1.20 (95% CI 0.82–1.75, Harrell's C  = 0.54), but in BRCA2 mutation carriers the association was significant ( OR for the lowest risk quintile relative to the highest was 0.47 (95% CI 0.33–0.69, Harrell's C  = 0.59). The 18 validated breast cancer SNPs differentiate breast cancer risks between women with BRCA2 mutations, but not BRCA1 . It may now be appropriate to use these SNPs to help women with BRCA2 mutations make maximally informed decisions about management options.

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