Renal Cell Carcinoma Onset at ≤ 46 Years Could Serve as Marker for Genetic Testing


Key Points

  • Use of the bottom 10th percentile of age in general population cases—ie, age ≤ 46 years—had a sensitivity of 70% and specificity of 90% for hereditary cases.
  • The number needed to test to identify one hereditary case in the bottom 10th percentile was estimated at 7 to 28.

Approximately 5% to 8% of renal cell carcinoma cases are hereditary, and there are no guidelines for patient selection for germline mutation testing in this disease. In a study reported in the Journal of Clinical Oncology, Shuch et al from the National Cancer Institute assessed whether age at onset could indicate the need for germline mutation testing for detection of inherited forms of kidney cancer. They found that age ≤ 46 years at onset could serve as a marker for genetic testing.

Study Details

In the study, age distributions of renal cell carcinoma cases were analyzed among 106,224 kidney cancer cases in the general population identified in the Surveillance, Epidemiology, and End Results (SEER)-17 database (1990–2008) and in 608 cases in the National Cancer Institute hereditary kidney cancer population.

Age Distributions

The mean and median ages of patients at onset of renal cell carcinoma in SEER-17 were 63.4 and 64 years, with the age distribution closely approaching normal distribution. Estimated ages at the bottom 25th, 10th, and 2.5th percentiles were 54, 46, and 36 years. Significant differences in mean ages were found between men and women (62.9 vs 64.3 years, P < .001), among clear cell, papillary, chromophobe, and collecting duct cancers 61.9, 62.5, 60.1, and 61.8 years; (P < .001 for trend), and between white and Asian patients (63.9 and 62.6 years) and black and Native American patients (60.7 and 60.3 years; P < .001). There were small differences in sex, histology, and race distribution in the bottom 10th percentile.

The mean and median ages at onset for the 608 National Cancer Institute cohort patients with hereditary kidney cancer were 39.3 years and 37 years (P < .001 compared with SEER-17 cohort); mean and median ages by type of syndrome were 35 and 35.4 years for von Hippel-Lindau syndrome (n = 387), 50 and 50.3 years for Birt-Hogg-Dubé syndrome (n = 127), 41 and 42.1 years for hereditary papillary renal cell carcinoma (n = 25), 37 and 41 years for hereditary leiomyomatosis and renal cell carcinoma (n = 56), and 32 and 34.3 years for succinate dehydrogenase B renal cell carcinoma (n = 13).

10th Percentile Threshold

The proportions of hereditary cases captured by age percentile in the SEER-17 general population age distribution (sensitivities) were 85% in the bottom 25th percentile, 70% in the 10th percentile and 46% in the 2.5th percentile. The specificities for these percentiles were 75%, 90%, and 98%.

A receiver operating characteristic model showed that the 10th percentile threshold for identifying hereditary cases on the basis of age alone would maximize sensitivity and specificity. Using an estimated incidence range for monogenic hereditary renal cell carcinoma of 0.5% to 2.0% in the renal cell carcinoma population (representing 25% to 50% of conservative estimates), the number needed to test to identify one case of hereditary renal cell carcinoma would be 7 to 28 in the 10th percentile compared with 3 to 7 in the 2.5th percentile and 14 to 59 in the 25th percentile.  

The investigators concluded, “Early age of onset might be a sign of hereditary [renal cell carcinoma]. Even in the absence of clinical manifestations and personal/family history, an age of onset of 46 years or younger should trigger consideration for genetic counseling/germline mutation testing and may serve as a useful cutoff when establishing genetic testing guidelines.”

W. Marston Linehan, MD, of the National Cancer Institute, is the corresponding author for the Journal of Clinical Oncology article.

The study was supported by grants from the National Institutes of Health. The study authors reported no potential conflicts of interest.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.