Prospectively measured triiodothyronine levels are positively associated with breast cancer risk in postmenopausal women

Introduction: The potential association between hypo-and hyperthyroid disorders and breast cancer has been investigated in a large number of studies during the last decades without conclusive results. This prospective cohort study investigated prediagnostic levels of thyrotropin (TSH) and triiodothyronine (T3) in relation to breast cancer incidence in pre- and postmenopausal women. Methods: In the Malmo Preventive Project, 2,696 women had T3 and/or TSH levels measured at baseline. During a mean follow-up of 19.3 years, 173 incident breast cancer cases were retrieved using record linkage with The Swedish Cancer Registry. Quartile cut-points for T3 and TSH were based on the distribution among all women in the study cohort. A Cox's proportional hazards analysis was used to estimate relative risks (RR), with a confidence interval (CI) of 95%. Trends over quartiles of T3 and TSH were calculated considering a P-value < 0.05 as statistically significant. All analyses were repeated for pre-and peri/postmenopausal women separately. Results: Overall there was a statistically significant association between T3 and breast cancer risk, the adjusted RR in the fourth quartile, as compared to the first, was 1.87 (1.12 to 3.14). In postmenopausal women the RRs for the second, third and fourth quartiles, as compared to the first, were 3.26 (0.96 to 11.1), 5.53 (1.65 to 18.6) and 6.87 (2.09 to 22.6), (P-trend: < 0.001). There were no such associations in pre-menopausal women, and no statistically significant interaction between T3 and menopausal status. Also, no statistically significant association was seen between serum TSH and breast cancer. Conclusions: This is the first prospective study on T3 levels in relation to breast cancer risk. T3 levels in postmenopausal women were positively associated with the risk of breast cancer in a dose-response manner

Family psychosocial characteristics influencing criminal behaviour and mortality - possible mediating factors: a longitudinal study of male and female subjects in the Stockholm Birth Cohort

Background: Family psychosocial characteristics in childhood have been associated with children's development into criminal behaviour and mortality. This study explored these possible relationships and examined alcohol and/or drug use and mental problems as possible mediating factors, highlighting gender-specific patterns. Methods: Data from Swedish subjects born in 1953 (n = 14,294) from the Stockholm Birth Cohort study were examined. Several indicators of adverse family factors and individual problems were included in the present study. The information was derived from various data sources, covering different periods. Gender-specific associations with incidence of criminality (1966-1980) and mortality (1981-2009) were analysed using logistic regression. Furthermore, the population attributable fraction (PAF) was calculated for all variables in the fully adjusted models which were positively related to the outcome. Results: Overall incidence of criminality and mortality was (m/f 32.3/6.6) and (m/f 6.1/3.5), respectively. The results showed that all aspects of family psychosocial and individual problems studied were associated with criminality for both genders. Among males, individual problems seemed to partly mediate these relations, but the associations remained statistically significant. Interestingly, the PAF analysis revealed a reduction in criminality of 17.5% when individual problems with alcohol and/or drug use were considered. Among females, a significant impact of alcohol and/or drug use on the association between family psychosocial characteristics and subsequent criminality was obtained. Inclusion of father's occupational class only somewhat reduced the estimates for the genders. Concerning male mortality, father's alcohol abuse was significantly related to an increased risk. When individual criminality was accounted for, the association was substantially reduced but remained statistically significant. Among females, when adjusting for family psychosocial factors, only the association between parents' mental problems and females' mortality was significant. None of the individual problem variables managed to explain this association. Conclusions: Family psychosocial characteristics were associated with both subsequent criminal behaviour and mortality. These connections were partly explained by individual risk factors, especially by alcohol and/or drug use. The practical implications of the findings point to the importance of addressing the individual's alcohol and/or drug use in reducing criminal behaviour, which would also lower the mortality rates.</p

Tipping the Balance: Sclerotinia sclerotiorum Secreted Oxalic Acid Suppresses Host Defenses by Manipulating the Host Redox Environment

Sclerotinia sclerotiorum is a necrotrophic ascomycete fungus with an extremely broad host range. This pathogen produces the non-specific phytotoxin and key pathogenicity factor, oxalic acid (OA). Our recent work indicated that this fungus and more specifically OA, can induce apoptotic-like programmed cell death (PCD) in plant hosts, this induction of PCD and disease requires generation of reactive oxygen species (ROS) in the host, a process triggered by fungal secreted OA. Conversely, during the initial stages of infection, OA also dampens the plant oxidative burst, an early host response generally associated with plant defense. This scenario presents a challenge regarding the mechanistic details of OA function; as OA both suppresses and induces host ROS during the compatible interaction. In the present study we generated transgenic plants expressing a redox-regulated GFP reporter. Results show that initially, Sclerotinia (via OA) generates a reducing environment in host cells that suppress host defense responses including the oxidative burst and callose deposition, akin to compatible biotrophic pathogens. Once infection is established however, this necrotroph induces the generation of plant ROS leading to PCD of host tissue, the result of which is of direct benefit to the pathogen. In contrast, a non-pathogenic OA-deficient mutant failed to alter host redox status. The mutant produced hypersensitive response-like features following host inoculation, including ROS induction, callose formation, restricted growth and cell death. These results indicate active recognition of the mutant and further point to suppression of defenses by the wild type necrotrophic fungus. Chemical reduction of host cells with dithiothreitol (DTT) or potassium oxalate (KOA) restored the ability of this mutant to cause disease. Thus, Sclerotinia uses a novel strategy involving regulation of host redox status to establish infection. These results address a long-standing issue involving the ability of OA to both inhibit and promote ROS to achieve pathogenic success

Breast tumor copy number aberration phenotypes and genomic instability

BACKGROUND: Genomic DNA copy number aberrations are frequent in solid tumors, although the underlying causes of chromosomal instability in tumors remain obscure. Genes likely to have genomic instability phenotypes when mutated (e.g. those involved in mitosis, replication, repair, and telomeres) are rarely mutated in chromosomally unstable sporadic tumors, even though such mutations are associated with some heritable cancer prone syndromes. METHODS: We applied array comparative genomic hybridization (CGH) to the analysis of breast tumors. The variation in the levels of genomic instability amongst tumors prompted us to investigate whether alterations in processes/genes involved in maintenance and/or manipulation of the genome were associated with particular types of genomic instability. RESULTS: We discriminated three breast tumor subtypes based on genomic DNA copy number alterations. The subtypes varied with respect to level of genomic instability. We find that shorter telomeres and altered telomere related gene expression are associated with amplification, implicating telomere attrition as a promoter of this type of aberration in breast cancer. On the other hand, the numbers of chromosomal alterations, particularly low level changes, are associated with altered expression of genes in other functional classes (mitosis, cell cycle, DNA replication and repair). Further, although loss of function instability phenotypes have been demonstrated for many of the genes in model systems, we observed enhanced expression of most genes in tumors, indicating that over expression, rather than deficiency underlies instability. CONCLUSION: Many of the genes associated with higher frequency of copy number aberrations are direct targets of E2F, supporting the hypothesis that deregulation of the Rb pathway is a major contributor to chromosomal instability in breast tumors. These observations are consistent with failure to find mutations in sporadic tumors in genes that have roles in maintenance or manipulation of the genome

The association between types of regular primary care and hospitalization among people with and without multimorbidity: A household survey on 25,780 Chinese

Using data collected from 25,780 Hong Kong citizens in a household survey, this study aimed to investigate the association between having regular source of primary care and hospitalization amongst people with and without multimorbidity (two or more chronic conditions). Potential interaction effects of regular primary care with multimorbidity were also examined. Results revealed a significant association between having regular source of primary care from General Practitioners and reduced hospitalization amongst respondents with multimorbidity (RR = 0.772; 95% CI = 0.667–0.894), adjusting for other potential confounding factors (i.e., socio-demographic factors and medical insurance and benefits). In contrast, having regular Specialist care was significantly associated with increased risk of hospitalization among both people with multimorbidity (RR = 1.619; 95% CI = 1.256–2.087) and without multimorbidity (RR = 1.981; 95% CI = 1.246–3.149), adjusting for potential confounders. A dose-response relationship between the number of chronic diseases and hospitalization was also observed, regardless of whether participants had regular source of primary care or not; relative risks and predicted probabilities for hospitalization were generally greater for those without regular source of primary care. Further studies are warranted to explore the role of healthcare system, informatics, organizational and practice-related factors on healthcare and functional outcomes