Seven of the 19 markers were significant in a multivariate predictive model of familial breast cancer in AJ women, three novel SNPs [rs17663555(5q13.2), rs566164(6q21), and rs11075884(16q22.2)], the FGFR2 haplotype, and three previously published SNPs [rs13387042(2q35), rs2046210(ESR1), and rs3112612(TOX3)], yielding moderate predictive power with an area under the curve (AUC) of the ROC (receiver-operator characteristic curve) of 0.74.
Features of hereditary breast cancer include an early age-of-onset and over-representation of the 'triple-negative' phenotype (negative forestrogen-receptor, progesterone-receptor and HER2).
Our results indicate for the first time the importance of inherited variants in the estrogen receptor coactivator genes PPARGC1A and PPARGC1B for familial breast cancer susceptibility.
For example, if tamoxifen reduces the risk of breast carcinoma via its antiestrogenic effects, it is possible that this effect will be diminished in the largely estrogen receptor negative BRCA1-related hereditary breast carcinoma.
The correlation reported previously, as well as our current findings, suggest that further investigations are warranted to understand the possible linkage of the ER gene locus to hereditary breast cancer.