1. A Large Case-Control Study Performed in Spanish Population Suggests That RECQL5 Is the Only RECQ Helicase Involved in Breast Cancer Susceptibility
- Author
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Erik Michel Marchena-Perea, Milton Eduardo Salazar-Hidalgo, Alicia Gómez-Sanz, Mónica Arranz-Ledo, Alicia Barroso, Victoria Fernández, Hugo Tejera-Pérez, Guillermo Pita, Rocío Núñez-Torres, Luz Pombo, Rafael Morales-Chamorro, Juana María Cano-Cano, Maria del Carmen Soriano, Pilar Garre, Mercedes Durán, María Currás-Freixes, Miguel de la Hoya, Ana Osorio, European Commission, Federación Española de Enfermedades Raras, Unión Europea. Comisión Europea, and Centro de Investigación Biomédica en Red - CIBERER (Enfermedades Raras)
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SPECTRUM ,Cancer Research ,GENES ,Oncology ,Breast cancer (BC) ,breast cancer (BC) ,RECQ helicase family ,next-generation sequencing ,BRCAX ,Next-generation sequencing ,WOMEN ,VARIANTS ,MUTATION ,BLM - Abstract
Around 50% of the familial breast cancer (BC) cases are estimated to be caused by germline variants in known low-, moderate-, and high-risk susceptibility genes, while the other half is of unknown genetic origin. In the present study, we wanted to evaluate the role of the RECQ helicases, some of which have been studied in the past as candidates, with unclear results about their role in the disease. Using next-generation sequencing (NGS) technology, we analyzed the whole coding sequence of BLM, RECQL1, RECQL4, RECQL5, and WRN in almost 2000 index cases from BC Spanish families that had previously tested negative for the known BC susceptibility genes (BRCAX) and compared the results with the controls extracted from gnomAD. Our results suggest that BLM, RECQL1, RECQL4, and WRN do not play a major role in BC susceptibility. However, in the combined analysis, joining the present results with those previously reported in a series of 1334 BC Spanish patients and controls, we found a statistically significant association between Loss of Function (LoF) variants in RECQL5 and BC risk, with an OR of 2.56 (p = 0.009; 95% CI, 1.18–4.98). Our findings support our previous work and places the RECQL5 gene as a new moderate-risk BC gene., A.O. is partially funded by FIS PI19/00640 supported by FEDER funds and the Spanish Network on Rare Diseases (CIBERER). M.d.l.H. is partially funded by FIS PI20/00110 supported by FEDER funds.
- Published
- 2022
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