Mutagen sensitivity, tobacco smoking and breast cancer risk: a case–control study

Given the high incidence of breast cancer and that more than half of cases remain unexplained, the need to identify risk factors for breast cancer remains. Deficiencies in DNA repair capacity have been associated with cancer risk. The mutagen sensitivity assay (MSA), a phenotypic marker of DNA damage response and repair capacity, has been consistently shown to associate with the risk of tobacco-related cancers. Methods: In a case–control study of 164 women with breast cancer and 165 women without the disease, we investigated the association between mutagen sensitivity and risk of breast cancer using bleomycin as the mutagen. Results: High bleomycin sensitivity (>0.65 breaks per cell) was associated with an increased risk of breast cancer, with an adjusted odds ratio of 2.8 [95% confidence interval (CI) = 1.7–4.5]. Risk increased with greater number of bleomycin-induced chromosomal breaks (Ptrend = 0.01). The association between bleomycin sensitivity and breast cancer risk was greater for women who were black, premenopausal and ever smokers. Our data also suggest that bleomycin sensitivity may modulate the effect of tobacco smoking on breast cancer risk. Among women with hypersensitivity to bleomycin, ever smokers had a 1.6-fold increased risk of breast cancer (95% CI = 0.6–3.9, P for interaction between tobacco smoking and bleomycin sensitivity = 0.32). Conclusions: Increased bleomycin sensitivity is significantly associated with an increased risk of breast cancer in both pre- and postmenopausal women. Our observation that the effect of tobacco smoking on breast cancer risk may differ based on mutagen sensitivity status warrants further investigation

Myeloid-Derived Suppressor Cells (MDSCs) in Aged Mice: Focus on Inflammation

As people get older, the homeostatic functions of many systems in the body like the immune system decline, which contributes to increase susceptibility to disease. The bone marrow of healthy individuals continually generates myeloid cells, which differentiate into mature cells like granulocytes, macrophages, or dendritic cells. However, under inflammatory conditions, there is an increased frequency of immature myeloid cells that can suppress T cell responses in peripheral secondary lymph organs in both human and murine hosts. The heterogeneous population of cells known as myeloid-derived suppressor cells (MDSCs), consisting of myeloid progenitors and immature myeloid cells, share a biological function: immunosuppression. This chapter reviews novel findings in mice about the nature of MDSCs and, in this context, discusses current knowledge about these cells during the aging process. MDSCs may have an important role in the regulation of the immune response during aging. MDSC dysfunction in aged mice may compromise the innate and adaptive immune systems, and thus understanding their role during aging may be useful for potential future therapeutics.Fil: Pistoresi, Maria Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Harman, María Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Castell, Sofía Daiana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentin