**8. Surveillance in hereditary kidney cancer families**

Recommendations for follow-up care should correspond to the level of risk associated with the genetic variant tested [43]. The aim of the monitoring is to improve the early detection of cancer in families with hereditary renal cancer. Monitoring recommendations includes regular kidney imaging: the healthy carrier of a gene mutation predisposing to kidney cancer will usually undergo abdominal MRI scans on a regular basis (**Table 7**). The frequency of follow-up depends on the biological nature of the family syndrome. Several monitoring planes have been proposed for hereditary kidney cancer syndromes, for example, by Freifeld [54] and Carlo [10]. Also, PDQ Cancer Information Summaries [55] has a suggestion for surveillance in certain syndromes predisposing to hereditary renal cancer.

Tracking intervals may be less frequent, for example, for HPRC, and more frequent for others, such as HLRCC in the case of an early onset of 10 years [56] and several reported cases among children. However, the estimated risk of developing RCC before age 20 is estimated to be only around 1–2%, whereas the lifetime risk of RCC among *FH* mutation carriers is approximately 15% [25]. In 2014, consensus guidelines from an international HLRCC symposium recommended annual renal MRI starting at age 8 to 10 years, as also recommended by the HLRCC Family Alliance and the French National Cancer Institute [25]. The starting age is still variable. In HPRC patients, if the tumor smaller than 3 cm is found, imaging should be repeated within the first year to assess the growth rate [55]. Generally, patients with renal


patients, as the knowledge on hereditary kidney cancer genes is still limited. This investigation

Genetic Susceptibility to Kidney Cancer http://dx.doi.org/10.5772/intechopen.91933 13

Tumor tissue-only gene tests by next generation sequencing with targeted genes may be soon routinely used for cancer patients' pharmacogenetic genotyping and analyzing their tumor tissue's somatic mutations to tailor their medical treatment [58]. The same method could be also a first step analysis for identifying the hereditary cancer mutation in a gene that is known in literature as a susceptibility gene. An additional test of patient's peripheral lymphocyte

The growing knowledge on the biology of hereditary kidney cancer produces information about driver genes in kidney cancer tumorigenesis and may develop diagnostics and therapeutic methods for kidney cancer in general [59]. Knowledge on evidence-based medicine in metastatic hereditary kidney cancer [60] is under active study. Analysis of induced pluripotent stem cells (iPSC) from HPRC pointed that drug screening and precision medicine are possible for hereditary kidney cancer [61]. Preventive medicine may be achieved for healthy persons

Prospective studies about the method of follow-up in healthy persons with family kidney cancer susceptibility mutation are warranted. The optimal onset to start follow-up in *FH*related hereditary kidney cancer families should be clarified as currently there is no consensus. It is known that the prognosis in early-stage kidney cancer disease is better than in later stages [62]. Studies about long-term effect of surveillance in healthy carriers in hereditary kidney cancer families are needed. Additionally, further research is needed to understand the actual

Knowledge on the clinical significance of mutations helps to improve prognosis in families with hereditary cancer. Understanding of hereditary kidney cancer syndromes on their molecular basis improves the utility of specific diagnosis [64]. In the future, increased knowledge of cancer genetics is likely to enable the development of targeted drug therapies. Today, hereditary mutations are detected by DNA testing of white blood cell lymphocytes. Tumor tissue-

should then be used to confirm the susceptive mutation as hereditary mutation.

with familial mutation predisposing to kidney cancer [61].

impact of genetic testing on young family members [63].

only tests to identify the hereditary kidney cancer are not yet available.

1 Department of Clinical Genetics, Turku University Hospital, Finland

is not available currently.

**10. Conclusion**

**Author details**

Minna Kankuri-Tammilehto1,2\*

\*Address all correspondence to: mikanku@utu.fi

2 Institute of Biomedicine, University of Turku, Finland

**Table 7.** Follow-up care recommendations in hereditary cancer syndromes in which the kidney cancer risk is high [10, 25, 54].

tumors associated with HPRC are candidates for radiologic surveillance until one or more tumors reach 3 cm. Ultrasound is not sufficient in surveillance of hereditary kidney cancer syndromes [10, 25, 54, 55]. In the near future, more evidence on effective monitoring in different kidney cancer syndromes will be gathered. If the gene mutation has not been identified but the family has a significantly increased risk of kidney cancer, a regular renal imaging examination in the first-degree relative of the patient with renal cancer may be considered on a case-by-case basis. Other surveillance procedures depend on the risks of the specific symptoms in observed gene mutation. In multisystem syndromes, monitoring practices depend on the probability of the kidney cancer, and ultrasound may be used in monitoring.

In Lynch syndrome, which is a high risk for upper tract ureotelic carcinoma, the risk of colorectal cancer can be reduced by removing intestinal adenomas at regular checkups, which results in the same mortality to colorectal cancer in the carriers of Lynch gene mutation as in the general population.
