Bioinformatics analysis of circulating miRNAs related to cancer following spinal cord injury

Patients with spinal cord injury (SCI) have an increased risk of developing esophageal, bladder and hematologic malignancies compared with the normal population. In the present study, we aimed to identify, through in silico analysis, miRNAs and their target genes related to the three most frequent types of cancer in individuals with SCI. In a previous study, we reported a pattern of expression of miRNAs in 17 sedentary SCI males compared with 22 healthy able-bodied males by TaqMan OpenArray. This list of miRNAs deregulated in SCI patients was uploaded to miRWALK2.0 to predict the target genes and pathways of selected miRNAs. We used Cytoscape software to construct the network displaying the miRNAs and their gene targets. Among the down-regulated miRNAs in SCI, 21, 19 and 20 miRNAs were potentially associated with hematological, bladder and esophageal cancer, respectively, and three target genes (TP53, CCND1 and KRAS) were common to all three types of cancer. The three up-regulated miRNAs were potentially targeted by 18, 15 and 10 genes associated with all three types of cancer. Our current bioinformatics analysis suggests the potential influence of several miRNAs on the development of cancer in SCI. In general, these data may provide novel information regarding potential molecular mechanisms involved in the development of cancer among individuals with SCI. Further studies aiming at understanding how miRNAs contribute to the development of the major cancers that affect patients after SCI may help elucidate the role of these molecules in the pathophysiology of the disease.39CAPES - Coordenação de Aperfeiçoamento de Pessoal e Nível SuperiorFAPESP – Fundação de Amparo à Pesquisa Do Estado De São PauloSem informação2017/23563-

On the avoidability of breast cancer in industrialized societies: older mean age at first birth as an indicator of excess breast cancer risk

Background Breast cancer incidence continuous to increase. We examined at population level the association between the relative excess risk of breast cancer and previous age of mother at first birth. Method Incidence of breast cancer in 34 industrialized countries was obtained from the GLOBOCAN 2002 and SEER databases. Data on age of mother at first birth was collected through national statistics offices. National relative excess risk (RER) was calculated by subtracting the lowest age-specific incidence rate from the rate in each population, and dividing the difference by the latter. Results The national RER in 2002 correlated closely with a higher average age at first birth in 1972, 1982, 1992 and also 2002, Pearson correlation [r] being 0.83, 0.79, 0.72 and 0.61, respectively; P < 0.0001. RER of breast cancer in 2002 for those aged 15–44 years correlated closely with the mean age at first birth in 1982 and 1992 (r: 0.81 and 0.75; P < 0.0001), whereas RER for those aged 45–54 years correlated strongly with age at first birth in 1972 and 1982 (r: 0.81 and 0.76; P < 0.0001), and for those aged 55–64 years with age at first birth in 1972 (r: 0.77; P < 0.0001). Conclusions The rising age at first childbirth of mothers has been followed by marked increases in breast cancer incidence. Later age at first birth seems to characterize secular diffusion of ‘modern’ lifestyles with a potentially large impact on increased breast cancer risk, and hence should be accompanied by greater opportunities for prevention through modifiable risk factors

Neurodevelopment of children exposed in utero to treatment of maternal malignancy

Cancer is the second most common cause of death during the reproductive years, complicating approximately 1/1000 pregnancies. The occurrence of cancer during gestation is likely to increase as a result of a woman's tendency to delay childbearing. Improved diagnostic techniques for malignancies increases detection of cancer during pregnancy. Malignant conditions during gestation are believed to be associated with an increase in poor perinatal and fetal outcomes that are often due to maternal treatment. Physicians should weigh the benefits of treatment against the risks of fetal exposure. To date, most reports have focused on morphologic observations made very close to the time of delivery with little data collected on children's long-term neurodevelopment following in utero exposure to malignancy and treatment. Because the brain differentiates throughout pregnancy and in early postnatal life, damage may occur even after first trimester exposure. The possible delayed effects of treatment on a child's neurological, intellectual and behavioural functioning have never been systematically evaluated. The goal of this report was to summarize all related issues into one review to facilitate both practitioners' and patients' access to known data on fetal risks and safety. © 2001 Cancer Research Campaign http://www.bjcancer.co

Parity-related molecular signatures and breast cancer subtypes by estrogen receptor status

INTRODUCTION: Relationships of parity with breast cancer risk are complex. Parity is associated with decreased risk of postmenopausal hormone receptor–positive breast tumors, but may increase risk for basal-like breast cancers and early-onset tumors. Characterizing parity-related gene expression patterns in normal breast and breast tumor tissues may improve understanding of the biological mechanisms underlying this complex pattern of risk. METHODS: We developed a parity signature by analyzing microRNA microarray data from 130 reduction mammoplasty (RM) patients (54 nulliparous and 76 parous). This parity signature, together with published parity signatures, was evaluated in gene expression data from 150 paired tumors and adjacent benign breast tissues from the Polish Breast Cancer Study, both overall and by tumor estrogen receptor (ER) status. RESULTS: We identified 251 genes significantly upregulated by parity status in RM patients (parous versus nulliparous; false discovery rate = 0.008), including genes in immune, inflammation and wound response pathways. This parity signature was significantly enriched in normal and tumor tissues of parous breast cancer patients, specifically in ER-positive tumors. CONCLUSIONS: Our data corroborate epidemiologic data, suggesting that the etiology and pathogenesis of breast cancers vary by ER status, which may have implications for developing prevention strategies for these tumors

Beliefs and perceptions about the causes of breast cancer: a case-control study

Background: Attributions of causality are common for many diseases, including breast cancer. The risk of developing breast cancer can be reduced by modifications to lifestyle and behaviours to minimise exposure to specific risk factors, such as obesity. However, these modifications will only occur if women believe that certain behaviours/lifestyle factors have an impact on the development of breast cancer. Method: The Breast Cancer, Environment and Employment Study is a case-control study of breast cancer conducted in Western Australia between 2009 and 2011. As part of the study 1109 women with breast cancer and 1633 women without the disease completed a Risk Perception questionnaire in which they were asked in an open-ended question for specific cause/s to the development of breast cancer in themselves or in others. The study identified specific causal beliefs, and assessed differences in the beliefs between women with and without breast cancer. Results: The most common attributions in women without breast cancer were to familial or inherited factors (77.6%), followed by lifestyle factors, such as poor diet and smoking (47.1%), and environmental factors, such as food additives (45.4%). The most common attributions in women with breast cancer were to mental or emotional factors (46.3%), especially stress, followed by lifestyle factors (38.6%) and physiological factors (37.5%), particularly relating to hormonal history.Conclusions: While the majority of participants in this study provided one or more causal attributions for breast cancer, many of the reported risk factors do not correspond to those generally accepted by the scientific community. These misperceptions could be having a significant impact on the success of prevention and early detection programs that seek to minimise the pain and suffering caused by this disease. In particular, women who have no family history of the disease may not work to minimise their exposure to the modifiable risk factors