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RAD51C and RAD51D have been defined as susceptibility genes for hereditary breast and ovarian cancer syndrome in several studies. In the present study, a mutation analysis of these genes was performed on non BRCA1/2 families. RAD51C and RAD51D genes were analyzed in 141 and 77 families, respectively. The analysis included direct sequencing and multiple ligation probe analysis. The RAD51C pathogenic variant c.404G > A was identified in a breast and ovarian cancer family (0.7%), while the RAD51D pathogenic variant c.694C > T was described in an ovarian cancer family (1.3%). Moreover, three unknown clinical significance variants were detected: c.307T > G in RAD51C, and c.413A > G and c.715C > T in RAD51D. No large genomic rearrangements (LGRs) were found. RAD51D carriers suffered from premenopausal ovarian tumors. These results increase our knowledge about the RAD51C and RAD51D mutation spectrum and support the notion that these genes should be included in the gene panel testing performed on patients with hereditary breast and ovarian cancer syndrome., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Background: The involvement of iron in anthracycline cardiotoxicity is supported by extensive experimental data, and by the preventive efficacy of dexrazoxane, an iron chelator. However, no clinical evidence of anthracycline-induced cardiac iron accumulation is available and the influence of previous iron overload or of genetic factors in human-induced heart disease is largely unknown. Our aim was to test the hypothesis that anthracyclines increase iron heart concentration and that HFE genotype modulates this iron deposit., Methods: We retrospectively evaluated cardiac events, cardiac iron and HFE genotype in 97 consecutive necropsies from patients with solid and hematological neoplasms. Heart and liver iron concentration was determined by atomic absorption spectroscopy. HFE gene mutations (C282Y and H63D) linked to hereditary hemochromatosis were analyzed by Fluorescence Resonance Energy Transfer (FRET) genotyping., Results: Heart iron concentration was increased in cases treated with a cumulative doxorubicin dose greater than 200mg/m(2) (490 vs 240 μg/g; p=0.01), independently of liver iron load or transfusion history. HFE mutated haplotypes 282C/63D (p=0.049) and 282Y/63H (p=0.027) were associated to higher cardiac iron deposits. The haplotype C282Y-Y/H63D-H interacted with anthracyclines for increasing cardiac iron load. In a multivariate linear regression analysis both HFE genotypes and anthracyclines contributed to heart iron concentration (R(2)=0.284)., Conclusions: Our data support the occurrence of an HFE-modulated heart iron accumulation in individuals treated with anthracyclines, independently of systemic iron load. If prospectively confirmed, iron-related parameters might be useful as predictive factors for anthracycline cardiotoxicity., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)