Estudio de polimorfismos de genes reparadores del ADN en cáncer de mama

[EN] Background: DNA repair is a fundamental mechanism for maintaining genome integrity of individuals and the deficit has been associated with different forms of cancer. On the other hand, many of the treatments used against these tumors, tumors act through direct induction of DNA damage and repair of these injuries is considered one of the main mechanisms of resistance to these drugs. Polymorphisms in DNA repair genes that condition a decrease in its function have been associated with both breast cancer risk (CM) and responses to different forms of treatment. To analyze the relationship XRCC3Thr241Met, XPDLys751Gln XRCC1Arg399Gln and the risk of breast cancer, age at diagnosis and response to treatment. Methods: We conducted an association study of cases and controls, and independently, a radio studio and genomic medicine. We included 174 women with CM and 300 controls. Germline DNA genotyping was performed by PCR-RFLP and Q-PCR. Results: The allele XRCC1Arg399Gln Gln was more frequent among cases than controls, associated with an increased risk of CM (p = 0.002, OR: 1.96. 95% CI 1.3-3). The alleles which have better repair capacity associated with the diagnosis of CM at later ages, but the difference was statistically significant only for XPD751Lys/Lys. None of the polymorphisms was associated with acute or chronic skin toxicity after RT XRCC3241Met/Met XRCC1399Arg/Arg and were associated with better disease free survival (p = 0.007, HR: 0.4, 95% CI 0.2 to 0.9) and overall survival (p = 0.027, HR: 0.15, 95% from 0.02 to 0.99) respectively, in patients with early-stage CM treated with anthracyclines. Conclusions: XRCC1399Gln is associated with risk of CM. XPD751Lys/Lys, is associated with the diagnosis of CM at later ages. XRCC1Arg399Gln could XRCC3Thr241Met and pharmacogenomic implications for selecting the most appropriate treatment for patients with CM in early stages.

Author

• Castro Marcos, Elena

• Tesis y disertaciones académicas
• Universidad de Salamanca (España)
• Academic dissertations
• Oncología clínica
• Clinical Oncology

Identifier

hdl:10366/83216

OAI identifier oai:identifier

oai:gredos.usal.es:10366/83216