Germline RAD51B truncating mutation in a family with cutaneous melanoma

Wadt, Karin; Aoude, Lauren G.; Golmard, Lisa; Hansen, Thomas V.O.; Sastre-Garau, Xavier; Hayward, Nicholas K.; Gerdes, Anne–Marie

doi:10.1007/s10689-015-9781-4

Cited by 14 publications

(13 citation statements)

References 19 publications

(21 reference statements)

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“…The discrepancy may be attributed to differences in sample size, ethnic populations, and study design, as well as the different roles of HRR genes in diverse cancers. However, the risk implication of RAD51B variants seems to be an exception, which has been robustly replicated in different studies on breast cancer , nasopharyngeal carcinoma , glioma , and cutaneous melanoma , suggesting the significant role of RAD51B variants in cancer risk.…”

Section: Discussionmentioning

confidence: 95%

Genetic variants within microRNA‐binding site of RAD51B are associated with risk of cervical cancer in Chinese women

et al. 2016

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RAD51B plays a central role in homologous recombinational repair (HRR) of DNA double‐strand breaks (DSBs), which is important to prevent genomic instability, a hallmark of cancer. Recent studies suggested that common genetic variants of RAD51B may contribute to cancer susceptibility. In this study, we aimed to investigate whether potentially functional variants within miRNA‐binding sites of RAD51B are associated with risk of cervical cancer. A total of 1486 cervical cancer patients and 1536 cancer‐free controls were enrolled, and two genetic variants, rs963917 (A > G) and rs963918 (T > C), were genotyped in all participants. Using multivariate logistic regression analyses, we found that G allele of rs963917 conferred lower risk of cervical cancer compared to A allele (adjusted OR = 0.89, 95% CI = 0.80–0.99, P = 0.039). Similarly, rs963918 allele C was associated with a decreased risk for cervical cancer compared with allele T (adjusted OR = 0.84, 95% CI = 0.74–0.94, P = 0.004). Haplotype analyses showed that haplotype GC was also correlated with lower risk (OR = 0.83, 95% CI = 0.73–0.95, P = 0.005) compared with the most common haplotype AT. In summary, our study suggested that miRNA‐binding site genetic variants of RAD51B may modify the susceptibility to cervical cancer, which is important to identify individuals with differential risk for this malignancy and to improve the effectiveness of preventive intervention.

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Section: Discussionmentioning

confidence: 95%

Genetic variants within microRNA‐binding site of RAD51B are associated with risk of cervical cancer in Chinese women

et al. 2016

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“…We and others have detected BRCA1 / 2 germline variants that lead to aberrant splicing and are, therefore, pathogenic [97,98,99,100,101,102]. Germline mutations that affect RNA-splicing are found in many other cancer genes, like RAD51B and CDKN2A , which play a role in familiar melanoma and pancreatic cancer cases [103,104,105,106]. Splicing mutations are also frequently found in NF-1 , causing neurofibromatosis type-1 [107].…”

Section: Inherited Cancer Syndromesmentioning

confidence: 99%

Next-Generation Sequencing in Oncology: Genetic Diagnosis, Risk Prediction and Cancer Classification

Kamps

Brandão

Bosch

et al. 2017

IJMS

389

294

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Next-generation sequencing (NGS) technology has expanded in the last decades with significant improvements in the reliability, sequencing chemistry, pipeline analyses, data interpretation and costs. Such advances make the use of NGS feasible in clinical practice today. This review describes the recent technological developments in NGS applied to the field of oncology. A number of clinical applications are reviewed, i.e., mutation detection in inherited cancer syndromes based on DNA-sequencing, detection of spliceogenic variants based on RNA-sequencing, DNA-sequencing to identify risk modifiers and application for pre-implantation genetic diagnosis, cancer somatic mutation analysis, pharmacogenetics and liquid biopsy. Conclusive remarks, clinical limitations, implications and ethical considerations that relate to the different applications are provided.

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“…Furthermore, it should be stressed that other SNPs within the last intron of RAD51B , and not in LD with those presented here, were involved in the susceptibility to breast cancer in males, and females . Germline mutations within RAD51B were also found to confer predisposition to familial breast and ovarian cancer, and cutaneous melanoma …”

Section: Discussionmentioning

confidence: 54%

“…47 Germline mutations within RAD51B were also found to confer predisposition to familial breast and ovarian cancer, 48 and cutaneous melanoma. 49 Subsequently, we also investigated the potential, although minor, involvement of other SNPs in DNA repair by a hypothesis-generating approach, which means a less conservative adjustment for multiple testing as applies for Bonferroni adjustment. Various htSNPs resulted significantly associated after BSGoF correction for multiple testing and confirmed and provided further evidence for our hypothesis of the relevance of DNA MMR and HR pathways for colon and rectal subtypes, respectively.…”

Section: Discussionmentioning

confidence: 99%

DNA repair and cancer in colon and rectum: Novel players in genetic susceptibility

Pardini

Corrado

Paolicchi

et al. 2019

Intl Journal of Cancer

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Interindividual differences in DNA repair systems may play a role in modulating the individual risk of developing colorectal cancer. To better ascertain the role of DNA repair gene polymorphisms on colon and rectal cancer risk individually, we evaluated 15,419 single nucleotide polymorphisms (SNPs) within 185 DNA repair genes using GWAS data from the Colon Cancer Family Registry (CCFR) and the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), which included 8,178 colon cancer, 2,936 rectum cancer cases and 14,659 controls. Rs1800734 (in MLH1 gene) was associated with colon cancer risk (p‐value = 3.5 × 10−6) and rs2189517 (in RAD51B) with rectal cancer risk (p‐value = 5.7 × 10−6). The results had statistical significance close to the Bonferroni corrected p‐value of 5.8 × 10−6. Ninety‐four SNPs were significantly associated with colorectal cancer risk after Binomial Sequential Goodness of Fit (BSGoF) procedure and confirmed the relevance of DNA mismatch repair (MMR) and homologous recombination pathways for colon and rectum cancer, respectively. Defects in MMR genes are known to be crucial for familial form of colorectal cancer but our findings suggest that specific genetic variations in MLH1 are important also in the individual predisposition to sporadic colon cancer. Other SNPs associated with the risk of colon cancer (e.g., rs16906252 in MGMT) were found to affect mRNA expression levels in colon transverse and therefore working as possible cis‐eQTL suggesting possible mechanisms of carcinogenesis.

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Germline RAD51B truncating mutation in a family with cutaneous melanoma

Cited by 14 publications

References 19 publications

Genetic variants within microRNA‐binding site of RAD51B are associated with risk of cervical cancer in Chinese women

Genetic variants within microRNA‐binding site of RAD51B are associated with risk of cervical cancer in Chinese women

Next-Generation Sequencing in Oncology: Genetic Diagnosis, Risk Prediction and Cancer Classification

DNA repair and cancer in colon and rectum: Novel players in genetic susceptibility

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