To review the current state of genetic risk models for predicting the development of kidney cancer, by identifying and comparing the performance of published models.
Risk models were identified from a recent systematic review and the Cancer-PRS web directory. A narrative synthesis of the models, previous validation studies and related genome-wide association studies (GWAS) was carried out. The discrimination and calibration of the identified models was then assessed and compared in the UK Biobank (UKB) cohort (cases = 452, controls=487,925).
Thirty-nine genetic models predicting the development of kidney cancer were identified and thirty-one were validated in UKB. Several of the genetic-only models (n=7/25) and most of the mixed genetic-phenotypic models (n=5/6) had some discriminatory ability (area-under the receiver operating curve > 0.5) in this cohort. In general, models containing a larger number of genetic variants identified in GWAS performed better than models containing a small number of variants associated with known causal pathways. However, the performance of the included models was consistently poorer than genetic risk models for other cancers.
Although there is potential for genetic models to identify those at highest risk of developing kidney cancer, their performance is poorer than the best genetic risk models for other cancers. This may be due to the comparatively small number of genetic variants associated with kidney cancer identified in GWAS to date. The development of improved genetic risk models for kidney cancer is dependent on the identification of more variants associated with this disease. Whether these will have utility within future kidney cancer screening pathways is yet to determined.
BJU international. 2022 Apr 22 [Epub ahead of print]
Hannah Harrison, Nicole Li, Catherine L Saunders, Sabrina H Rossi, Joe Dennis, Simon J Griffin, Grant D Stewart, Juliet A Usher-Smith
Department of Public health and Primary Care, University of Cambridge, Cambridge, UK., Department of Surgery, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.