JU INSIGHT Family History and Risk of Renal Cell Carcinoma: A National Multiregister Case-Control Study

By: Rasmus G. Jakobsson, MD, Sahlgrenska Center for Cancer Research, Sahlgrenska Academy, University of Gothenburg, Sweden, Region Västra Götaland, Skaraborgs Hospital, Skövde, Sweden; Salmir Nasic, MSc, Sahlgrenska Academy, University of Gothenburg, Sweden, Region Västra Götaland, Skaraborgs Hospital, Skövde, Sweden; Ola Bratt, MD, PhD, Sahlgrenska Academy, University of Gothenburg, Sweden, Region Västra Götaland, Sahlgrenska University Hospital, Gothenborg, Sweden; Martin E. Johansson, MD, PhD, Sahlgrenska Center for Cancer Research, Sahlgrenska Academy, University of Gothenburg, Sweden, Sahlgrenska University Hospital, Gothenburg, Sweden; Anna Grenabo Bergdahl, MD, PhD, Sahlgrenska Academy, University of Gothenburg, Sweden, Region Västra Götaland, Sahlgrenska University Hospital, Gothenborg, Sweden | Posted on: 19 Jan 2024

Jakobsson RG, Nasic S, Bratt O, Johansson ME, Grenabo Bergdahl A. Family history and risk of renal cell carcinoma: a national multiregister case-control study. J Urol. 2024;211(1):71-79.

Study Need and Importance

Available studies of hereditary risk in renal cell carcinoma (RCC) are mainly based on questionnaires with a high risk of recall bias. We investigated the association between family history of RCC and RCC risk.

What We Found

We used national population-based registers to identify RCC patients, first-degree relatives (FDRs; parents and siblings), and established RCC diagnosis among FDR. In this Swedish data set of 9416 patients with RCC, 3.1% had 1 or more FDR previously diagnosed with RCC (familial RCC). There was no statistical difference in median age between sporadic RCC and familial RCC. Matched case/control comparison indicates that people with an FDR with RCC have an approximately doubled risk of being diagnosed with RCC themselves, with a higher risk increase for women than for men. Having 2 or more FDRs was very rare but associated with a sixfold increased risk (Table). Familial RCC was strongly associated with bilateral and multifocal tumors.

Table. First-Degree Relatives With Renal Cell Carcinoma as Risk Factor for Renal Cell Carcinoma

	All patients
	Case (%)	Control (%)	OR (95% CI) CLR
No. FDRs with RCC	n = 5169	n = 52,364
0	4875 (94)	50,807 (97)	Reference
≥1	294 (6)	1557 (3.0)	1.89 (1.65-2.16)
≥2^a	9	14	6.05 (2.37-15.45)
Having father as FDR with RCC	n = 6104	n = 61,818
No	5991 (98)	61,207 (99)	Reference
Yes	113 (1.9)	611 (1.0)	1.91 (1.55-2.35)
Having mother as FDR with RCC	n = 6388	n = 64,689
No	6290 (98.5)	64,177 (99)	Reference
Yes	98 (1.5)	512 (0.8)	1.88 (1.51-2.35)
Having sibling as FDR with RCC	n = 5462	n = 55,326
No	5373 (98)	54,880 (99)	Reference
Yes	89 (1.6)	446 (0.8)	1.97 (1.55-2.50)
Abbreviations: CLR, conditional logistic regression; FDR, first-degree relative; OR, odds ratio; RCC, renal cell carcinoma. ^a Separate model was performed for ≥2 FDR with RCC and compared to reference FDR = 0.

Limitations

Registered FDRs were missing for 36% of the studied population (31% mother, 35% father, 42% sibling). This could be due to emigration, a very old index case, or unknown relatives. However, the loss of data on mother, father or siblings was equal between cases and controls. Adjustment for potential inheritable environmental risk factors was not possible. This study was based on information from 1 country only, which may affect external validity.

Interpretation for Patient Care

The risk of RCC is approximately doubled if a parent or sibling has RCC, but the absolute risk is small. The median age at diagnosis in this group is similar to sporadic RCC, suggesting that known hereditary cancer syndromes constitute only a small proportion of familial RCC. Having 2 FDRs with RCC is associated with a much-increased risk of RCC and might be an indication for screening.