RECQL5 – Breast Cancer

Population-based case–control studies have evaluated common RECQL5 polymorphisms in breast cancer risk. In a Chinese cohort of 510 breast cancer patients and 510 matched controls, the rs820196 C allele (42.5 % vs 34.3 %, P<0.001) and CC genotype (16.7 % vs 9.4 %, P<0.001) and the rs828200 G allele (52.7 % vs 43.8 %, P<0.001) and GG genotype (23.7 % vs 18.0 %, P<0.001) were significantly enriched in cases, and the C–G haplotype conferred increased risk (OR = 2.247, 95 % CI 1.854–2.721) while C–T and T–G haplotypes were protective ([PMID:25394896]). In an admixed U.S. non-Hispanic white and Hispanic cohort (3,592 cases, 4,183 controls), several RECQL5 single nucleotide variants showed modest associations with breast cancer, further supporting a risk‐modifying role ([PMID:23629941]). These studies lack familial segregation data and focus on common alleles.

Functional and mechanistic assays demonstrate that RECQL5 helicase maintains genome stability by disrupting RAD51 nucleoprotein filaments and promoting synthesis‐dependent strand annealing, suppressing aberrant recombination events. Mutational disruption of the RECQL5 BRC‐variant reduces RAD51 binding, increases sister chromatid exchanges, and heightens sensitivity to replication stress in human cells, while Drosophila recq5 mutants exhibit elevated DNA damage sensitivity to cisplatin. Together, the genetic associations and concordant functional data suggest RECQL5 as a low‐penetrance tumor suppressor in breast cancer. Key Take-home: RECQL5 polymorphisms confer modest breast cancer risk and mechanistically align with its role in DNA repair, informing risk stratification and potential therapeutic targeting.

References

• Tumour biology • 2014 • Association between RECQL5 genetic polymorphisms and susceptibility to breast cancer. PMID:25394896
• Genes, chromosomes & cancer • 2013 • Telomere length, telomere-related genes, and breast cancer risk: the breast cancer health disparities study. PMID:23629941

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