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Resumo(s)
Background: MMR is responsible for the repair of base-base mismatches and insertion/deletion loops. Besides this, MMR is also associated with an anti-recombination function, suppressing homologous recombination. Losses of heterozygosity and/or microsatellite instability have been detected in a large number of skin samples from breast cancer patients, suggesting a potential role of MMR in breast cancer susceptibility. Methods: We carried out a hospital-based case-control study in a Caucasian Portuguese population ( 287 cases and 547 controls) to estimate the susceptibility to non-familial breast cancer associated with some polymorphisms in mismatch repair genes (MSH3, MSH4, MSH6, MLH1, MLH3, PMS1 and MUTYH). Results: Using unconditional logistic regression we found that MLH3 (L844P, G>A) polymorphism GA (Leu/Pro) and AA (Pro/Pro) genotypes were associated with a decreased risk: OR = 0.65 (0.45-0.95) ( p = 0.03) and OR = 0.62 (0.41-0.94) ( p = 0.03), respectively. Analysis of two-way SNP interaction effects on breast cancer revealed two potential associations to breast cancer susceptibility: MSH3 Ala1045Thr/MSH6 Gly39Glu - AA/TC [ OR = 0.43 (0.21-0.83), p = 0.01] associated with a decreased risk; and MSH4 Ala97Thr/MLH3 Leu844Pro - AG/AA [ OR = 2.35 (1.23-4.49), p = 0.01], GG/AA [ OR = 2.11 (1.12-3,98), p = 0.02], and GG/AG [ adjusted OR = 1.88 (1.12-3.15), p = 0.02] all associated with an increased risk for breast cancer. Conclusion: It is possible that some of these common variants in MMR genes contribute significantly to breast cancer susceptibility. However, further studies with a large sample size will be needed to support our results.
Descrição
We wish to thank our colleague Prof. Antonio S. Rodrigues for expert scrutiny of the manuscript. Our appreciation and thanks are extended to Luisa Manso Oliveira, Lylliane Luz, Silvia Morgado Amaro and Maria Catarina Soveral for technical support, and Claudia Leiras for the critical reading of the manuscript. Center for Research in Human Molecular Genetics (CIGMH), Projects POCTI/QUI/57110/2004 from Fundacao da Ciencia e Tecnologia (FCT) and Fundacao Calouste Gulbenkian ( Grant 69405) support our current research. The PhD grant SFRH/BD/17828/2004 from FCT is also acknowledged.
Palavras-chave
POLYMORPHISMS LUNG MICROSATELLITE INSTABILITY RISK BRCA2 DNA MECHANISMS MLH3 HMSH2 CARCINOMA Lung cancer Endobronchial ultrasound Endoscopic ultrasound Fine needle aspiration Diagnosis SDG 3 - Good Health and Well-being