Leptin and leptin receptor polymorphisms are associated with increased risk and poor prognosis of breast carcinoma

BACKGROUND: Leptin (LEP) has been consistently associated with angiogenesis and tumor growth. Leptin exerts its physiological action through its specific receptor (LEPR). We have investigated whether genetic variations in LEP and LEPR have implications for susceptibility to and prognosis in breast carcinoma. METHODS: We used the polymerase chain reaction and restriction enzyme digestion to characterize the variation of the LEP and LEPR genes in 308 unrelated Tunisian patients with breast carcinoma and 222 healthy control subjects. Associations of the clinicopathologic parameters and these genetic markers with the rates of the breast carcinoma-specific overall survival (OVS) and the disease free survival (DFS) were assessed using univariate and multivariate analyses. RESULTS: A significantly increased risk of breast carcinoma was associated with heterozygous LEP (-2548) GA (OR = 1.45; P = 0.04) and homozygous LEP (-2548) AA (OR = 3.17; P = 0.001) variants. A highly significant association was found between the heterozygous LEPR 223QR genotype (OR = 1.68; P = 0.007) or homozygous LEPR 223RR genotype (OR = 2.26; P = 0.001) and breast carcinoma. Moreover, the presence of the LEP (-2548) A allele showed a significant association with decreased disease-free survival in breast carcinoma patients, and the presence of the LEPR 223R allele showed a significant association with decreased overall survival. CONCLUSION: Our results indicated that the polymorphisms in LEP and LEPR genes are associated with increased breast cancer risk as well as disease progress, supporting our hypothesis for leptin involvement in cancer pathogenesis

Height and pancreatic cancer risk: A systematic review and meta-analysis of cohort studies

Background Greater height has been associated with increased risk of several cancers, but epidemiological data on height and pancreatic cancer are inconclusive. We conducted a systematic review and meta-analysis of prospective studies to clarify these results. Methods PubMed and several other databases were searched up to September 2011. Prospective studies of height and pancreatic cancer were included. Summary relative risks were estimated by the use of a random effects model. Results We identified twelve cohort studies that were included in the meta-analysis. The summary RR per 5-cm increase in height was 1.07 (95 % CI: 1.03-1.12, I2 = 57 %). The results were similar among men and women. The summary estimate was attenuated when we included results from two pooled analyses together with these studies, summary RR = 1.03 (95 % CI: 1.00-1.07, I2 = 44 %). Conclusions This meta-analysis of cohort studies provides further evidence that greater adult attained height is associated with increased pancreatic cancer risk. However, given the unexplained heterogeneity, further studies are needed before a conclusion can be drawn

Is adaptation reducing vulnerability or redistributing it?

As globalization and other pressures intensify the economic, social and biophysical connections between people and places, it seems likely that adaptation responses intended to ameliorate the impacts of climate change might end up shifting risks and vulnerability between people and places. Building on earlier conceptual work in maladaptation and other literature, this article explores the extent to which concerns about vulnerability redistribution have influenced different realms of adaptation practice. The review leads us to conclude that the potential for adaptation to redistribute risk or vulnerability is being given only sparse—and typically superficial—attention by practitioners. Concerns about ‘maladaptation’, and occasionally vulnerability redistribution specifically, are mentioned on the margins but do not significantly influence the way adaptation choices are made or evaluated by policy makers, project planners or international funds. In research, the conceptual work on maladaptation is yet to translate into a significant body of empirical literature on the distributional impacts of real-world adaptation activities, which we argue calls into question our current knowledge base about adaptation. These gaps are troubling, because a process of cascading adaptation endeavors globally seems likely to eventually re-distribute risks or vulnerabilities to communities that are already marginalized and vulnerable. We conclude by discussing the implications that the potential for vulnerability redistribution might have for the governance of adaptation processes, and offer some reflections on how research might contribute to addressing gaps in knowledge and in practice. WIREs Clim Change 2018, 9:e500. doi: 10.1002/wcc.500. This article is categorized under: Vulnerability and Adaptation to Climate Change &gt; Values-Based Approach to Vulnerability and Adaptation.</p

The Normativity of Rationality, by Benjamin Kiesewetter

The Normativity of Rationality, by Benjamin Kiesewetter. Oxford: Oxford University Press, 2017. Pp. xii + 314