Prevalence and Characteristics of Patients with Suspected Inherited Renal Cell Cancer: Application of the ACMG/NSGC Genetic Referral Guidelines to Patient Cohorts
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Patients with suspected hereditary renal cell cancer (RCC) are under-referred for genetic evaluation. Characterizing the prevalence and characteristics of suspected inherited RCC is a crucial step toward advancing personalized, genetically-based cancer risk management for patients and their families. To evaluate the prevalence and characteristics of suspected inherited RCC syndromes based on consensus criteria, we performed a cross-sectional analysis of patients with a diagnosis of RCC in SEER (2001–2011, n = 105,754) and in our institutional cancer registry (2004–2013, n = 998). Consensus criteria for referral of patients with RCC for genetic evaluation from the American College of Medical Genetics and Genomics and National Society of Genetic Counselors (ACMG/NSGC) were applied to the two cohorts. The associations between meeting referral criteria with demographic characteristics were assessed with chi-square tests. Overall, 24.0 % of the SEER cohort and 33.7 % of our institutional cohort met ACMG/NSGC referral criteria for genetic counseling. While white patients more commonly met early onset clear cell RCC criteria, black patients met papillary RCC criteria at twice the rate of whites in both cohorts (p < 0.0001). As many as 1 in 5 individuals with RCC meet referral criteria for genetic evaluation based on newly emerging guidelines, with differences in pathology noted by race. Prospective genetic testing studies utilizing emerging referral guidelines should help to refine the genetic spectrum of inherited kidney cancer. This study supports efforts to increase awareness of referral of patients with RCC for genetic counseling particularly among urologic providers.
KeywordsKidney cancer Genetic counseling Race Hereditary cancer syndromes
This project was supported by institutional funding from Sidney Kimmel Cancer Center of Thomas Jefferson University. We would like to thank Fran Guiles from the Thomas Jefferson University Hospital cancer registry staff for data collection. Veda N. Giri and Hong Truong had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Compliance with Ethical Standards
Conflict of Interest
Hong Truong, Sarah E. Hegarty, Leonard G. Gomella, William K. Kelly, Edouard J. Trabulsi, Costas D. Lallas, and Veda N. Giri declare that they have no conflict of interest.
Human Studies and Informed Consent
This study does not include human subjects. All data were abstracted from institutional and national cancer registries which did not contain any patient identifying information. The study was IRB-approved at Thomas Jefferson University.
This article does not contain any studies with animals performed by any of the authors.
- American Cancer Society: Targeted Therapies for Kidney Cancer. Cited April 29, 2016. Available at: http://www.cancer.org/cancer/kidneycancer/detailedguide/kidney-cancer-adult-treating-targeted-therapy.
- Benusiglio, P. R., Giraud, S., Deveaux, S., Méjean, A., Correas, J.-M., Joly, D., et al. (2014). Renal cell tumour characteristics in patients with the Birt-Hogg-Dubé cancer susceptibility syndrome: a retrospective, multicentre study. Orphanet Journal of Rare Diseases, 9(1), 163. doi: 10.1186/s13023-014-0163-z.CrossRefPubMedPubMedCentralGoogle Scholar
- Centers for Disease Control and Prevention. (2014). Public health genomics knowledge base version 1.0: Genomic application toolkit. Available at: https://www.cdc.gov/genomics/implementation/toolkit/tier1.htm. Accessed 15 May 2016.
- Ferlay, J., Soerjomataram, I., Dikshit, R., Eser, S., Mathers, C., Rebelo, M., et al. (2015). Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. International journal of cancer. Journal International Du Cancer, 136(5), E359–E386. doi: 10.1002/ijc.29210
- Genetics of Kidney Cancer (Renal Cell Cancer)–Health Professional Version (PDQ®). (2016) Cited April 29, 2016. Available at: http://www.cancer.gov/types/kidney/hp/kidney-genetics-pdq#link/_586_toc.
- Hampel, H., Bennett, R. L., Buchanan, A., Pearlman, R., Wiesner, G. L., Guideline Development Group, American College of Medical Genetics and Genomics Professional Practice and Guidelines Committee and National Society of Genetic Counselors Practice Guidelines Committee. (2015, January). A practice guideline from the American College of Medical Genetics and Genomics and the National Society of genetic counselors: referral indications for cancer predisposition assessment. Genetics in Medicine: Official Journal of the American College of Medical Genetics. doi: 10.1038/gim.2014.147
- Howlader, N., Noone, A. M., Krapcho, M., & Garshell, J. (2013). SEER cancer statistics review, 1975–2010. Based on November 2012 SEER data submission, posted to the SEER web site, April 2013. Bethesda (MD).Google Scholar
- Kiuru, M., Launonen, V., Hietala, M., Aittomäki, K., Vierimaa, O., Salovaara, R., et al. (2001). Familial cutaneous leiomyomatosis is a two-hit condition associated with renal cell cancer of characteristic histopathology. The American Journal of Pathology, 159(3), 825–829. doi: 10.1016/S0002-9440(10)61757-9.CrossRefPubMedPubMedCentralGoogle Scholar
- Linehan, W. M., Srinivasan, R., & Schmidt, L. S. (2010). The genetic basis of kidney cancer: a metabolic disease. Nature Reviews Urology.Google Scholar
- NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®): (2016a) Genetic/Familial High-risk Assessment: Breast and Ovarian (Version 2.2016). Available at: https://www.nccn.org/professionals/physician_gls/pdf/genetics_screening.pdf
- NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®): (2016b) Genetic/Familial High-Risk Assessment: Colorectal (Version 1.2016). Available at https://www.nccn.org/professionals/physician_gls/pdf/genetics_colon.pdf
- Patel, N. H., Attwood, K. M., Hanzly, M., Creighton, T. T., Mehedint, D. C., Schwaab, T., & Kauffman, E. C. (2015). Comparative analysis of smoking as a risk factor among renal cell carcinoma histological subtypes. The Journal of Urology, 194(3), 640–646. doi: 10.1016/j.juro.2015.03.125.CrossRefPubMedGoogle Scholar
- Reaume, M. N., Graham, G. E., Tomiak, E., Kamel-Reid, S., Jewett, M. A. S., Bjarnason, G. A., et al. (2013). Canadian guideline on genetic screening for hereditary renal cell cancers. Canadian Urological Association Journal = Journal De l'Association Des Urologues Du Canada, 7(9–10), 319–323. doi: 10.5489/cuaj.1496.CrossRefPubMedPubMedCentralGoogle Scholar
- Toro, J. R., Wei, M. H., Glenn, G. M., Weinreich, M., Toure, O., Vocke, C., et al. (2008). BHD mutations, clinical and molecular genetic investigations of Birt-Hogg-Dubé syndrome: a new series of 50 families and a review of published reports. Journal of Medical Genetics, 45(6), 321–331. doi: 10.1136/jmg.2007.054304.CrossRefPubMedPubMedCentralGoogle Scholar
- Wei, M. H., Toure, O., Glenn, G. M., Pithukpakorn, M., Neckers, L., Stolle, C., et al. (2006). Novel mutations in FH and expansion of the spectrum of phenotypes expressed in families with hereditary leiomyomatosis and renal cell cancer. Journal of Medical Genetics, 43(1), 18–27. doi: 10.1136/jmg.2005.033506.CrossRefPubMedGoogle Scholar