Establishing effective registration systems in resource-limited settings: cancer registration in Kumasi, Ghana.

Cancer control programs are needed worldwide to combat the increases in cancer incidence and mortality predicted for sub-Saharan Africa in the next decades. The effective design, implementation, and evaluation of such programs require population-based cancer registries. Ghana's second largest medical center, the Komfo Anokye Teaching Hospital (KATH) in Kumasi, has made initial progress at developing a cancer registry. This registry, however, is housed in the medical oncology/radiotherapy center at KATH and does not currently include data from other departments that also interact with cancer patients. The aim of this study was to improve KATH cancer registration by compiling cancer data from other major departments that see cancer patients. Using recent population estimates, we calculated crude cancer incidence rates of the "minimally-reported cases" for the Ashanti region. The most common cancers found in this study were breast (12.6 per 100,000), cervix (9.2 per 100,000), and prostate (8.8 per 100,000). These cancers occur at similar crude incidence rates in other West African countries. Females had overall higher incidence rates than males, which is consistent throughout the West African region. This study identified a number of methodological challenges facing cancer registries in Ghana that can be addressed to improve the quality of cancer registries in other resource-limited settings. Such registries should be tailored to the local health system context. A lack of coordination among the sources reporting cancer cases and a lack of understanding of local health-care systems and payment plans may interfere with the quality, completeness, and comparability of data from cancer registries in resource-limited settings. Steps, barriers, and solutions for improving cancer registration in Ghana and countries at similar levels are discussed.

Regulation of the ATM-activator protein Aven by CRM1-dependent nuclear export.

Aven is a regulator of apoptosis whose overexpression is associated with poor prognosis in several cancers, including childhood acute lymphoblastic leukemia and acute myeloid leukemia. We have recently shown that Aven serves as an activator and substrate of ATM, thereby modulating the DNA-damage response and G(2)/M cell cycle progression. Under physiological conditions, the cellular localization of Aven is mainly cytosolic, but a small fraction of the protein is present in the nucleus. Here, we show that treatment of cells with leptomycin B, an inhibitor of Exportin-1/CRM (chromosomal region maintenance) 1, resulted in nuclear accumulation of Aven. Furthermore, we identified a functional LR-NES between amino acid residues 282-292 of the human Aven protein, a sequence that is evolutionary conserved among a range of vertebrate species. Disruption of this LR-NES by site-directed mutagenesis resulted in enhanced nuclear localization of Aven, but did not alter the ability of the protein to induce G(2)/M cell cycle arrest in interphase Xenopus laevis extracts. However, elimination of the LR-NES sequence led to a reduction in the capacity of Aven to arrest Xenopus oocytes containing intact nuclei. Our results suggest that the regulation of nucleocytoplasmatic traffic of Aven could modulate its ability to influence cell cycle progression.