Incidence and survival of oesophageal and gastric cancer in England between 1998 and 2007, a population-based study

BACKGROUND: Major changes in the incidence of oesophageal and gastric cancers have been reported internationally. This study describes recent trends in incidence and survival of subgroups of oesophageal and gastric cancer in England between 1998 and 2007 and considers the implications for cancer services and policy. METHODS: Data on 133,804 English patients diagnosed with oesophageal and gastric cancer between 1998 and 2007 were extracted from the National Cancer Data Repository. Using information on anatomical site and tumour morphology, data were divided into six groups; upper and middle oesophagus, lower oesophagus, oesophagus with an unspecified anatomical site, cardia, non-cardia stomach, and stomach with an unspecified anatomical site. Age-standardised incidence rates (per 100,000 European standard population) were calculated for each group by year of diagnosis and by socioeconomic deprivation. Survival was estimated using the Kaplan-Meier method. RESULTS: The majority of oesophageal cancers were in the lower third of the oesophagus (58%). Stomach with an unspecified anatomical site was the largest gastric cancer group (53%). The incidence of lower oesophageal cancer increased between 1998 and 2002 and remained stable thereafter. The incidence of cancer of the cardia, non-cardia stomach, and stomach with an unspecified anatomical site declined over the 10 year period. Both lower oesophageal and cardia cancers had a much higher incidence in males compared with females (M:F 4:1). The incidence was also higher in the most deprived quintiles for all six cancer groups. Survival was poor in all sub-groups with 1 year survival ranging from 14.8-40.8% and 5 year survival ranging from 3.7-15.6%. CONCLUSIONS: An increased focus on prevention and early diagnosis, especially in deprived areas and in males, is required to improve outcomes for these cancers. Improved recording of tumour site, stage and morphology and the evaluation of focused early diagnosis programmes are also needed. The poor long-term survival reinforces the need for early detection and multidisciplinary care

Predisposition to Cancer Caused by Genetic and Functional Defects of Mammalian Atad5

ATAD5, the human ortholog of yeast Elg1, plays a role in PCNA deubiquitination. Since PCNA modification is important to regulate DNA damage bypass, ATAD5 may be important for suppression of genomic instability in mammals in vivo. To test this hypothesis, we generated heterozygous (Atad5+/m) mice that were haploinsuffficient for Atad5. Atad5+/m mice displayed high levels of genomic instability in vivo, and Atad5+/m mouse embryonic fibroblasts (MEFs) exhibited molecular defects in PCNA deubiquitination in response to DNA damage, as well as DNA damage hypersensitivity and high levels of genomic instability, apoptosis, and aneuploidy. Importantly, 90% of haploinsufficient Atad5+/m mice developed tumors, including sarcomas, carcinomas, and adenocarcinomas, between 11 and 20 months of age. High levels of genomic alterations were evident in tumors that arose in the Atad5+/m mice. Consistent with a role for Atad5 in suppressing tumorigenesis, we also identified somatic mutations of ATAD5 in 4.6% of sporadic human endometrial tumors, including two nonsense mutations that resulted in loss of proper ATAD5 function. Taken together, our findings indicate that loss-of-function mutations in mammalian Atad5 are sufficient to cause genomic instability and tumorigenesis