Renal Cancer

Renal cancer Renal cancer currently accounts for ~3% of adult malignancies worldwide (300,000 new cases out of approximately 11 million), and it is particularly prevalent in some parts of the EU where it's the 10th most common cancer overall (Ferlay J, Bray F, Pisani P, Parkin DM (Eds.; 2004) Globocan 2002 - Cancer Incidence, Mortality and Prevalence Worldwide (IARC CancerBase No. 5, version 2.0). Lyon: IARC). Over 80% of renal cancers are renal cell carcinomas (RCCs) that arise in the renal parenchyma. Because surgical resection of the kidney is a standard intervention in RCC, extensive amounts of fresh tumour and non-tumour tissue are available. This, together with several compelling clinical needs as described below, have led to the International Cancer Genome Consortium (ICGC) recognising that RCC is a particularly appropriate tumour for the proposed investigations, but a national or international initiative that combines sufficient clinical and genomic resources for these studies has yet to emerge. Indeed, RCC is one of the few tumour types for which there are currently no biological markers that are in routine clinical use and for which there are few treatment options due to its inherent resistance to chemo- and radiotherapy. The clinical and biological materials brought together with large-scale genomic analysis in this project will provide the information to address this issue so as to provide further understanding of the disease aetiology and heterogeneity leading to new diagnostic tools and design of targeted treatments.

Renal cancer is of particular significance within Europe, as the incidence rates are very high in areas of Central Europe and some other European regions compared to elsewhere in the world (Fig. 1). In the Czech Republic, the national incidence exceeds that of any other country worldwide (Ferlay et al, IARC CancerBase No. 5, version 2.0, 2004). Current incidence rates in the Czech Republic are around 23/100,000 cases per year among men, and 13/100,000 among women. Outside of central Europe, similar high kidney cancer rates are also reported within the US among African American populations, whereas the lowest incidence rates in both men and women are found in Africa and Asia. A sharp recent increase in the incidence has also been observed, most notably in the Czech Republic and among the black population in the USA (Scelo and Brennan, Nat Clin Pract Urol 4: 205, 2007) The epidemiology of RCC is only moderately understood, with known lifestyle risk factors including tobacco smoking, obesity, hypertension and a history of diabetes, and these alone do not account for the marked ethnic and geographical variations in incidence. Approximately 50% of patients diagnosed with kidney cancer are alive after 5 years. There are also important geographical disparities for survival within Europe, being around 70% in Germany and Austria, and less than 50% in the UK. Survival is influenced not only by stage at diagnosis, but also by age, being on average 70% for cancers diagnosed before the age of 45, to 40% for cancers diagnosed at age 75 or over (Scelo and Brennan, Nat Clin Pract Urol 4:205, 2007).

Over 80% of RCC are histologically of conventional (clear cell) subtype. VHL gene mutations have been reported to occur in the majority of sporadic conventional RCC. Previous reports have indicated a mutation level of between 50% and 60%, although two recent large and independent analyses from CAGEKID PIs indicate that approximately 80% of tumours are likely to harbour VHL mutations or methylation changes (Nickerson et al. Clin Cancer Res 2008, Banks et al Cancer Res 2006). This is the only gene currently known to harbour frequent modifications in clear cell renal cancer. Identification of additional biological markers of the disease is likely to be important for further understanding of disease heterogeneity, and may help to explain differences in disease incidence and survival patterns across Europe and elsewhere.