What should we know about precarious employment and health in 2025? Framing the agenda for the next decade of research.

The generalization of flexible labour markets, the declining influence of unions and the degradation of social protection has led to the emergence of new forms of employment at the expense of the Standard Employment Relationship, as well as a considerable amount of research across social and scientific disciplines. Years ago we suggested the urgent need to disentangle the consequences of new types of employment for the health and well-being of workers, contending that the study of precarious employment and health is in its infancy. Today, research challenges include clearer, more precise definitions of the original concepts, a more detailed understanding of the pathways and mechanisms through which precarious employment harms worker health, stronger information systems for monitoring the problem and a complex systems approach to employment conditions and health research. All of these must be guided by the theoretical and policy debates linking precarious employment and health, and be geared towards developing better tools for the design, implementation and evaluation of policies intended to minimize precariousness in the labour market and its effects on public health and health inequalities. Our aim in this paper is to outline an agenda for the next decade of research on precarious employment and health, establishing a compelling programme that expands our understanding of complex causes and links.

Precarious employment: understanding an emerging social determinant of health.

Employment precariousness is a social determinant that affects the health of workers, families, and communities. Its recent popularity has been spearheaded by three main developments: the surge in "flexible employment" and its associated erosion of workers' employment and working conditions since the mid-1970s; the growing interest in social determinants of health, including employment conditions; and the availability of new data and information systems. This article identifies the historical, economic, and political factors that link precarious employment to health and health equity; reviews concepts, models, instruments, and findings on precarious employment and health inequalities; summarizes the strengths and weaknesses of this literature; and highlights substantive and methodological challenges that need to be addressed. We identify two crucial future aims: to provide a compelling research program that expands our understanding of employment precariousness and to develop and evaluate policy programs that effectively put an end to its health-related impacts.

Multiplex detection of hotspot mutations by rolling circle-enabled universal microarrays.

Detection of somatic low abundance mutations in early cancer development requires a discriminatory, specific, and high-throughput methodology. In this study we report specific, discriminatory detection of low abundance mutations through a novel combination of rolling circle amplification (Nat Genet 1998; 19:225-232) and PCR ligation detection reaction on a universal oligonucleotide microarray (J Mol Biol 1999; 292:251-262). After mutation-specific multiplex ligation and hybridization of 17 pairs of probes to a generic microarray, the ligated probes were visualized. The multiplex mutation-specific ligation is possible only because rolling circle amplification permits quantification of previously undetectable hybridization events conducive to the detection of a single mutation from within a pool of over 100 wild-type alleles. This system is readily adaptable to high-throughput automation using a robot such as the Biomek platform.

Developmental regulation of the concentrative nucleoside transporters CNT1 and CNT2 in rat liver.

BACKGROUND/AIMS: The pattern of nucleoside transporter expression in hepatocytes was studied in the developing rat liver. METHODS: Hepatocytes isolated from fetuses, neonates and adult rats were used for uridine uptake measurements and concentrative nucleoside transporter (CNT) expression. RESULTS: Adult hepatocytes showed the highest Na-dependent uridine uptake, but fetal hepatocytes exhibited a significant NBTI-sensitive component of equilibrative Na+-independent transport, which was either negligible or absent in neonatal and adult rat hepatocytes. Low Na+-dependent uridine uptake was associated with low amounts of CNT1 and CNT2 transporter proteins, both with apparent Km values in the low micromolar range. Hepatocyte primary cultures from 20-day-old fetuses showed very low amounts of CNT2 mRNA, and expressed both carrier proteins. Incubation of fetal hepatocytes with dexamethasone and T3 resulted in a significant increase in Na+-dependent uridine uptake and an accumulation of the CNT2 protein and mRNA. CONCLUSIONS: The expression of concentrative nucleoside carriers in hepatocytes from developing rat liver is developmentally regulated. Addition of endocrine factors known to induce differentiation of fetal hepatocytes results in selective up-regulation of CNT2 expression.

Analysis of adenomatous polyposis coli promoter hypermethylation in human cancer.

Germ-line mutations in the tumor suppressor gene APC are associated with hereditary familial adenomatous polyposis (FAP), and somatic mutations are common in sporadic colorectal tumors. We now report that methylation in the promoter region of this gene constitutes an alternative mechanism for gene inactivation in colon and other tumors of the gastrointestinal tract. The APC promoter is hypermethylated in 18% of primary sporadic colorectal carcinomas (n = 108) and adenoma (n = 48), and neoplasia with APC methylation fails to express the APC transcript. Methylation affects only wild-type APC in 95% of cases and is not observed in tumors from FAP patients who have germ-line APC mutations. As with APC mutation, aberrant APC methylation occurs early in colorectal carcinogenesis. When other tumor types are analyzed (n = 208), methylation of the APC promoter is not restricted to the colon but is present in tumors originating elsewhere in the gastrointestinal tract but rarely in other tumors. Our data suggest that hypermethylation of APC provides an important mechanism for impairing APC function and further underscores the importance of the APC pathway in gastrointestinal tumorigenesis.

DCC and SMAD4 alterations in human colorectal and pancreatic tumor dissemination.

Chromosome 18q is lost a high proportion of colorectal and pancreatic cancers. Three candidate tumor suppressor genes, DCC, Smad4 and Smad2 have been identified in this chromosome region. DCC and Smad4 aberrations have been previously identified in pancreatic and colorectal tumors. The aim of this study was to compare the presence of concurrent genetic aberrations in DCC and neighboring Smad4 and Smad2 genes during colorectal and pancreatic distal dissemination. We have used a panel of orthotopically implanted colorectal and pancreatic xenografts and corresponding metastases. We have shown that while LOH at DCC locus occurred at a similar frequency in both tumors, diminished DCC protein expression was exclusively present in colorectal tumors harboring intragenic DCC LOH. In contrast, in pancreatic xenografts loss of DCC protein and mRNA expression was restricted to metastases. Smad4 gene aberrations were detected at a similar frequency in both tumors and were selected for during distal dissemination. Acquisition of alterations in both genes occurred independently. Our results suggest that both DCC and Smad4 contribute to pancreatic and colorectal distal dissemination. However, the role of DCC may differ between both tumor types.

Orthotopic models of human pancreatic cancer.

Orthotopic transplantation of solid tumor fragments of human tumors in nude mice reproduces their pattern of local growth and distal dissemination. While lymphatic, hepatic or peritoneal dissemination can be reproduced, perineural invasion is absent. Early passages (less than 3) of xenografts show a high degree of stability regarding K-ras, p53 and p16 gene status. On the other hand, advanced passages of tumors acquire additional alterations in the p15 and Smad4 genes. Mutations in K-ras, p53, p15 and Smad4 genes can be acquired, in this model system, in the more advanced stages of pancreatic tumor dissemination. Finally, it is also possible to standardize local growth of these tumors as well as its dissemination pattern giving us a preclinical tool to evaluate the anticancer activity of new drugs.