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Epidemiology and Pathophysiology of Renal Cancer

Kidney Cancer Nursing Conference London May 2010

Dr Duncan Gilbert MA MRCP FRCR PhD Consultant Clinical Oncologist and Clinical Lecturer Sussex Cancer Centre, Brighton UK

Renal Cancer
UK
3% cancers in men (8th commonest) 2% women (rank 10) 5000 men per year, 3000 women

www.cancerresearchuk.org/cancerstats

Renal Cell Carcinoma

Renal Cancer increasing incidence


Figure 1.6: Age standardised (European) incidence rates, kidney cancer, by sex, Great Britain, 1975-2006
16 14 12 10 8 6 4 2 0
males females persons

Rate per 100,000 population

1975

1978

1981

1984

1987

1990

1993

1996

1999

2002

Year of diagnosis
www.cancerresearchuk.org/cancerstats

2005

Geographical Variation

www.cancerresearchuk.org/cancerstats

Risk Factors for RCC


General Medical Familial

Risk Factors for RCC: General

Age:
Sex: Obesity Smoking:

75% in over 60s M:F 3:2 precise link unclear ? responsible for approximately 25-50%(M) and 10-15% (F)

Risk Factors for RCC: Medical

Acquired cystic kidney disease Dialysis and transplantation Pelvic radiotherapy Recurrent UTIs / Urinary stones Hypertension Phenacetin

Risk Factors for RCC: Familial


Von Hippel Lindau (VHL) syndrome characterised by germline mutation of chromosome 3p and development of RCC Familial clear cell RCC Hereditary papillary RCC Papillary thyroid and papillary renal Birt Hogg Dube

Renal Cell Cancer - Genetics


CONDITION
Von Hippel Lindau Hereditary clear cell RCC Hereditary papillary RCC Birt Hogg Dub

PREDISPOSES TO
Clear cell RCC Clear cell RCC

GENE
VHL ?

CHROMOSOMAL LOCATION
3p25.5 ?

Papillary RCC

MET

7q34

Oncocytoma

BHD

17p11.2

Renal Cell Carcinoma : Histologic and Molecular Characteristics Proximal nephron


Clear cell carcinoma (75%)
VHL mutation in 50-80%, hypermethylation 5-20% Anti VEGF strategies

Papillary carcinoma(15%)
Type I c-met mutation Type II FH mutation

Distal nephron
Chromophobe (5%) Oncocytoma (5%)

Von Hippel Lindau (VHL)


VHL protein has important role in cellular response to hypoxia In normoxia VHL protein is bound to HIF and targets it for destruction In hypoxia HIF accumulates stimulating production of PDGF and VEGF that, in turn, stimulate angiogenesis and cellular proliferation. Inactivation of VHL seen in 70-80% clear cell RCCs Constitutive expression of oxygen-regulated transcription factor (HIFa) Induction of hypoxia-inducible genes, including vascular endothelial growth factor (VEGF) VEGF over expression promotes tumor angiogenesis and growth

Molecular Biology of RCC

Brugarolas J. NEJM, 2007.

Renal Cell Cancer - treatments


Hereditary link gives insights into tumour biology that form rationale for systemic therapy

Summary
Increasing incidence both real (obesity, smoking) and artifactual (increased imaging) Both result in increasing patient numbers requiring treatment Recent expansion of effective treatment options in metastatic setting further increases resources required to manage this patient group
duncan.gilbert@bsuh.nhs.uk