A Large Case-Control Study Performed in Spanish Population Suggests That RECQL5 Is the Only RECQ Helicase Involved in Breast Cancer Susceptibility

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.

Gene polymorphisms associated with sudden decreases in heart rate during extensive peritoneal lavage with distilled water after gastrectomy

“…According to a recent study, RECQL5 promotes metastasis and resistance to cisplatin in non-small cell lung cancer[ 15 ]. A large case-control study suggests that RECQL5 is a new moderate-risk breast cancer gene[ 16 ]. RECQL5 protein overexpression in breast cancer is strongly correlated with poor prognosis and survival, and with therapeutic resistance.…”

Understanding the Human RECQ5 Helicase—Connecting the Dots from DNA to Clinics

“…Similarly, a number of deletion and missense mutations affecting the function of the RECQ5 SRI domain have been identified in breast cancer cases [ 78 , 79 ], suggesting the significance of the anti-tumor properties associated with the RECQ5 SRI domain across multiple cancer types. In a large case–control study conducted on a Spanish population, RECQ5 emerged as the only RECQ helicase gene with mutations associated with breast cancer risk [ 78 , 79 ].…”

“…Similarly, a number of deletion and missense mutations affecting the function of the RECQ5 SRI domain have been identified in breast cancer cases [ 78 , 79 ], suggesting the significance of the anti-tumor properties associated with the RECQ5 SRI domain across multiple cancer types. In a large case–control study conducted on a Spanish population, RECQ5 emerged as the only RECQ helicase gene with mutations associated with breast cancer risk [ 78 , 79 ]. In addition to the RECQ5 variants identified within the SRI domain, a significant number of missense mutations associated with breast cancer were found in the conserved residues within the SFII domain ( Table 1 ) [ 78 , 79 ].…”

“…In a large case–control study conducted on a Spanish population, RECQ5 emerged as the only RECQ helicase gene with mutations associated with breast cancer risk [ 78 , 79 ]. In addition to the RECQ5 variants identified within the SRI domain, a significant number of missense mutations associated with breast cancer were found in the conserved residues within the SFII domain ( Table 1 ) [ 78 , 79 ]. For instance, residue G44, located immediately upstream of the first of the seven SFII motifs, is conserved among all RECQ helicases except WRN/RECQ3 [ 12 ].…”

The Expression Characteristics and Function of the RECQ Family in Pan-Cancer

“…Abnormal expression of RECQs has been related to the progression of different cancers and is correlated with unfavorable prognosis [ 13 , 14 ]. Recent studies indicate that RECQs may serve as potential genes responsible for breast cancer susceptibility, with missense mutations in these genes playing a role in the development of familial breast cancer [ 15 , 16 , 17 ]. In addition, RECQs are linked to thyroid carcinoma, prostate cancer, and ovarian cancer [ 18 , 19 ].…”