Background-RAD51D and RAD54L are involved in homologous recombination, and rare mutations in RAD51D were recently found in breast-ovarian cancer families. This study investigated RAD51D and RAD54L for mutations in breast and ovarian cancer patients in the

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Prostate cancer is the most frequently diagnosed cancer in men; however, the genetic basis of susceptibility remains elusive. The EMSY gene is located in the prostate cancer linked chromosome region at 11q13.5. The aim of this study was to screen EMSY for sequence variants and to evaluate its association with the risk of prostate cancer. We performed a Finnish population-based case-control study with 923 controls, 184 familial prostate cancer cases and 2,301 unselected prostate cancer cases. Variants were screened using sequencing and validated using the TaqMan assay and High Resolution Melting analysis. A total of 27 sequence variants were found, and 17 of them were novel. A rare intronic variant, IVS6-43A>G (minor allele frequency of 0.004), increased the prostate cancer risk in familial cases (odds ratio [OR] 5 7.5; 95% confidence interval [CI] 5 1.3-45.5; p 5 0.02). Further analysis with clinicopathological data revealed that the variant is associated with aggressive unselected cases (prostate specific antigen ! 20 lg/L or Gleason grade ! 7), based on both case-control (OR 5 6.0; 95% CI 5 1.3-26.4; p 5 0.03) and case-case analyses (OR 5 6.5; 95% CI 5 1.5-28.4; p 5 0.002). In addition, all variant-positive familial cases had aggressive cancer. Our results indicate that the intronic variant IVS6-43A>G increases the familial and unselected prostate cancer risk in a Finnish population and contributes to the aggressive progression of the disease in a high-penetrance manner. The potential role of the variant as a predictive genetic marker for aggressive prostate cancer should be further evaluated.

BackgroundRare, heterozygous germline mutations in the RAD51C gene have been found in breast and ovarian cancer families. In the Finnish population, we have identified two founder mutations in RAD51C that increase the risk of ovarian cancer but not breast cancer in the absence of ovarian cancer. Risk for other cancers has not been studied.MethodsTo study the role of RAD51C mutations in other common cancer types, we genotyped the Finnish RAD51C founder mutations c.837 + 1G > A and c.93delG in 1083 prostate cancer patients and 802 colorectal cancer patients using TaqMan Real-Time PCR.ResultsNo RAD51C mutations c.837 + 1G > A or c.93delG were detected among the prostate or colorectal cancer patients.ConclusionsThe results suggest that the RAD51C mutations do not predispose to prostate or colorectal cancer.

Background BRCA1 and BRCA2 mutations explain approximately one-fifth of the inherited susceptibility in high-risk Finnish hereditary breast and ovarian cancer (HBOC) families. EMSY is located in the breast cancer-associated chromosomal region 11q13. The EMSY gene encodes a BRCA2-interacting protein that has been implicated in DNA damage repair and genomic instability. We analysed the role of germline EMSY variation in breast/ovarian cancer predisposition. The present study describes the first EMSY screening in patients with high familial risk for this disease.MethodsIndex individuals from 71 high-risk, BRCA1/2-negative HBOC families were screened for germline EMSY sequence alterations in protein coding regions and exon-intron boundaries using Sanger sequencing and TaqMan assays. The identified variants were further screened in 36 Finnish HBOC patients and 904 controls. Moreover, one novel intronic deletion was screened in a cohort of 404 breast cancer patients unselected for family history. Haplotype block structure and the association of haplotypes with breast/ovarian cancer were analysed using Haploview. The functionality of the identified variants was predicted using Haploreg, RegulomeDB, Human Splicing Finder, and Pathogenic-or-Not-Pipeline 2.ResultsAltogether, 12 germline EMSY variants were observed. Two alterations were located in the coding region, five alterations were intronic, and five alterations were located in the 3'untranslated region (UTR). Variant frequencies did not significantly differ between cases and controls. The novel variant, c.2709 + 122delT, was detected in 1 out of 107 (0.9%) breast cancer patients, and the carrier showed a bilateral form of the disease. The deletion was absent in 897 controls (OR = 25.28; P = 0.1) and in 404 breast cancer patients unselected for family history. No haplotype was identified to increase the risk of breast/ovarian cancer. Functional analyses suggested that variants, particularly in the 3'UTR, were located within regulatory elements. The novel deletion was predicted to affect splicing regulatory elements.ConclusionsThese results suggest that the identified EMSY variants are likely neutral at the population level. However, these variants may contribute to breast/ovarian cancer risk in single families. Additional analyses are warranted for rare novel intronic deletions and the 3'UTR variants predicted to have functional roles.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-017-3488-x) contains supplementary material, which is available to authorized users.