A Large Case-Control Study Performed in Spanish Population Suggests That RECQL5 Is the Only RECQ Helicase Involved in Breast Cancer Susceptibility
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. BRCAX Cases
2.2. Controls
2.3. DNA Isolation
2.4. Next-Generation Sequencing
2.5. Bioinformatics Analysis and Variant Filtration
Gene | Reference | Nucleotide Change a | Protein Change | gnomAD c | CSVS d | Previously Found |
---|---|---|---|---|---|---|
RECQL1 | NM_002907.3 | c.84delT | p.Thr29ArgfsTer14 | NR | NR | |
BLM | NM_000057.2 | c.53_56delCCAG | p.Ala18GlufsTer7 | NR | NR | |
c.1933C>T | p.Gln645Ter | 0.00008810 | NR | [37] | ||
WRN | NM_000553.6 | c.205dupA | p.Ile69AsnfsTer2 | NR | NR | |
c.979G>T | p.Gly327Ter | NR | NR | |||
c.2604G>A | p.Trp868Ter | NR | NR | |||
c.4013del | p.Leu1338* | NR | NR | |||
c.4117_4120dupAGAT | p.Cys1374Ter | NR | NR | |||
RECQL4 | NM_004260.4 | c.320delA | p.Gln107ArgfsTer7 | NR | NR | |
c.447dupC | p.Ser150Leufs*8 | NR | NR | |||
c.1048_1049delAG b | p.Arg350GlyfsTer21 | NR | NR | |||
c.2161C>T | p.Arg721Ter | 0.00002179 | 1/2093 | [38] | ||
c.2269C>T | p.Gln757Ter | 0.0001494 | 1/2093 | [38] | ||
c.2547_2548del b | p.(Phe850Profs*33) | NR | 1/2093 | [39] | ||
c.3217del | p.(Thr1073Profs*8) | NR | NR |
Gene | Reference | Nucleotide Change | Protein Change | Phenotype b | gnomAD | CSVS |
---|---|---|---|---|---|---|
RECQL5 | NM_004259.6 | c.130G>A a | p.Gly44Ser | BC, 49 years | NR | NR |
c.657delC a | p.Cys220AlafsTer15 | BC, 34 years | 0.00005270 | 1/2037 | ||
c.2308C>T | p.Arg770Ter | BC, 44 years | 0.00003567 | 2/2037 | ||
c.2790C>T | p.(Lys931Serfs*14) | BC, 39 years | NR | NR | ||
c.2874C>G a | p.Ser958Arg | BC, 48 years | 0.0001085 | 2/2037 | ||
c.2874C>G | p.Ser958Arg | BC, 78 years | 0.0001085 | 2/2037 |
2.6. Case-Control Association Study
2.7. Combined Analysis
2.8. Splicing Studies
3. Results
3.1. RECQL1, BLM, WRN, and RECQL4 (Likely) Pathogenic Variants Are Not Associated with BC in Spanish BRCAX Cases
3.2. Analysis of RECQL5 (Likely) LoF Variants in 1993 BC-Only BRCAX Cases Shows a Tendency as a Moderate-Risk Gene Model
3.3. Selection of Potentially Damaging Missense and Synonymous Variants in the RECQ Helicases
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Gene | Cases-Heterozygotes/Non-Heterozygotes | Controls-Heterozygotes/Non-Heterozygotes a | Odds Ratio | p-Value | Confidence Interval |
---|---|---|---|---|---|
RECQL1 | 1/1992 | 132/51,061 b | 0.20 | 0.097 | 0.01–1.14 |
BLM | 2/1991 | 125/51,199 | 0.42 | 0.338 | 0.05–1.55 |
WRN | 5/1988 | 113/51,180 | 1.15 | 0.628 | 0.37–2.77 |
RECQL4 | 9/1984 | 209/50,447 | 1.10 | 0.721 | 0.50–2.13 |
RECQL5 | 6/1987 | 74/50,883 | 2.07 | 0.127 | 0.74–4.74 |
RECQL5c | 10/2683 | 74/50,883 | 2.56 | 0.009 | 1.18–4.98 |
Gene | Reference | Nucleotide Change | Protein Change | Phenotype | gnomAD | CSVS |
---|---|---|---|---|---|---|
RECQL5 | NM_004259.6 | c.130G>A | p.Gly44Ser | BC, 50 years | NR | NR |
c.657delC | p.Cys220AlafsTer15 | BiBC, 34 years, 46 years | 0.00005270 | 1/2037 | ||
c.2393dupC | p.Met799Aspfs*24 | BiBC, 37 years, 39 years | NR | NR | ||
c.2874C>G | p.Ser958Arg | BC, 26 years | 0.0001085 | 2/2037 |
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Marchena-Perea, E.M.; Salazar-Hidalgo, M.E.; Gómez-Sanz, A.; Arranz-Ledo, M.; Barroso, A.; Fernández, V.; Tejera-Pérez, H.; Pita, G.; Núñez-Torres, R.; Pombo, L.; et al. A Large Case-Control Study Performed in Spanish Population Suggests That RECQL5 Is the Only RECQ Helicase Involved in Breast Cancer Susceptibility. Cancers 2022, 14, 4738. https://doi.org/10.3390/cancers14194738
Marchena-Perea EM, Salazar-Hidalgo ME, Gómez-Sanz A, Arranz-Ledo M, Barroso A, Fernández V, Tejera-Pérez H, Pita G, Núñez-Torres R, Pombo L, et al. A Large Case-Control Study Performed in Spanish Population Suggests That RECQL5 Is the Only RECQ Helicase Involved in Breast Cancer Susceptibility. Cancers. 2022; 14(19):4738. https://doi.org/10.3390/cancers14194738
Chicago/Turabian StyleMarchena-Perea, Erik Michel, Milton Eduardo Salazar-Hidalgo, Alicia Gómez-Sanz, Mónica Arranz-Ledo, Alicia Barroso, Victoria Fernández, Hugo Tejera-Pérez, Guillermo Pita, Rocío Núñez-Torres, Luz Pombo, and et al. 2022. "A Large Case-Control Study Performed in Spanish Population Suggests That RECQL5 Is the Only RECQ Helicase Involved in Breast Cancer Susceptibility" Cancers 14, no. 19: 4738. https://doi.org/10.3390/cancers14194738