Renal cell carcinoma as first and second primary cancer: etiological clues from the Swedish Family-Cancer Database.

PURPOSE: An increasing incidence and improved prognosis of kidney cancer have led to concern about second primary malignancies. The study of multiple primary malignancies is also important since the association of certain malignancies may guide the search for germline alterations and environmental risk factors. We evaluated bidirectional associations between renal cell carcinoma and other primary cancers.
MATERIALS AND METHODS: We studied 8,030 patients with renal cell carcinoma based on the Swedish Family-Cancer Database. The SIR of second cancer was calculated by comparing it to the rate of first cancers. Followup was started in 1993 and continued through 2006.
RESULTS: A total of 677 patients had second cancers after the first renal cell carcinoma, including 89 second renal cell carcinomas. In 776 patients renal cell carcinoma was diagnosed after another primary cancer. Histology concordant renal cell carcinoma pairs showed a SIR of 31.04 and 15.15 after clear cell and total renal cell carcinoma, respectively. The highest SIR of 132.46 was noted for synchronous contralateral clear cell renal cell carcinoma. A reciprocally increased risk of renal cell carcinoma was seen after lung, breast, prostate, bladder, thyroid gland, adrenal gland and nervous system cancer as well as after melanoma and nonHodgkin's lymphoma. Clear cell renal cell carcinoma was also in excess after brain hemangioblastoma with a SIR of 70.79.
CONCLUSIONS: High risk was found for histology concordant renal cell carcinoma pairs and contralateral renal cell carcinoma. Bidirectional associations of renal cell carcinoma with many other cancers may imply etiological sharing. von Hippel-Lindau syndrome may explain the excess of renal cell carcinoma after brain hemangioblastoma.