**2. Identifying hereditary kidney cancer**

Hereditary kidney cancer syndrome is often characterized by an early age of onset (approximately 45 years) [30], typical histological pattern, and frequently the bilaterality and multicentricity of the primary tumor (**Table 1**). By evaluating the family history of diagnosed cancer cases, benign tumors, and diagnostic gene test results, it is possible to identify families with hereditary kidney cancer (**Tables 2** and **3**).

is linked to some congenital multisystem syndromes, such as Beckwith-Wiedemann syndrome and tuberous sclerosis (**Table 4**). When such a multisystemic syndrome is detected, appropri-

None Uterine leiomyomas in

Reference [13, 14] [15, 16] [17–20] [21, 22] [23]

It is suspected that hereditary kidney cancer is underdiagnosed. Identifying the families with increased risk for kidney cancer allows clinicians to improve the prognosis of persons with genetic cancer susceptibility. This review discussed the characteristics of inherited kidney

In hereditary and sporadic cancer, the normal genome regulation is impaired [34], and cancer susceptibility is caused by both inherited germline gene mutations and somatic gene mutations in tissue that occurred over time. However, in sporadic cases the inherited gene mutations cause low risk for kidney cancer [35]. Of all clear cell-type RCCs (sporadic or hereditary), 75% have a somatic mutation in the von Hippel-Lindau tumor suppressor gene (VHL) in the short

ate follow-up care is provided as with hereditary kidney cancer families.

cancer and how to improve their prognosis (**Table 5**).

**3. Basic cancer genetics**

**von Hippel-Lindau**

Bilaterality, multiple

tumors

Retinal

hemangioma/CNS hemangioblastoma, pheochromocytoma **Hereditary papillary RCC (HPRC)**

Clear cell carcinoma Papillary type 1 Papillary type 2,

Bilaterality, multiple tumors, microscopic lesions as much as 1000

or radical nephrectomy

**Table 2.** Hereditary cancer syndromes in which the kidney cancer risk is high.

Minimal invasive Minimal invasive

Gene *VHL MET FH FLCN(BHD)*

40 years 50–70 years Less than 40 years 50 years

**Hereditary leiomyomatosis and RCC (HLRCC)**

collecting duct

40% Nearly 100% 20–30% 30% 30%

Unilaterality, solitarity, aggressive, highly potential to metastasize

almost every patient, uterine leiomyosarcoma, cutaneous leiomyomas

**Birt-Hogg-Dubé (BHD)**

Bilaterality, multiple

Cutaneous hair follicle benign tumors and pulmonary cysts in almost every patient

tumors

Radical nephrectomy Minimal invasive

Most often chromophobe oncocytoma

**Constitutional chromosomal 3 translocation** 5

Clear cell carcinoma

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

> Bilaterality, multiple tumors

Thyroid, bladder, pancreatic and gastric cancer

**(VHL)**

RCC subtype

Risk for RCC

Typical age of onset for RCC

Biology of RCC

Typical surgery

Other signs of the syndrome than RCC

It is possible that there exists only a single hereditary cancer syndrome case in the family due to de novo mutations (autosomal dominant) which means that the person's parents do not have the same mutation. There are hot spot regions in genes where mutation can easier develop during meiosis of germ cells. In addition to this, the risk of hereditary kidney cancer

Atypically young age of onset for tumors of the syndrome

Relative with two tumors of the syndrome (two examples below)

• RCC and uterine leiomyosarcoma

• Colon cancer or endometrial carcinoma in the uterus and upper tract urothelial carcinoma

Typical histological finding (e.g., rare subtype or multiplicity) or clinical picture

**Table 1.** Factors suggesting inherited cancer syndrome.

Multiple close relatives with benign or malign tumors of the syndrome


**Table 2.** Hereditary cancer syndromes in which the kidney cancer risk is high.

is linked to some congenital multisystem syndromes, such as Beckwith-Wiedemann syndrome and tuberous sclerosis (**Table 4**). When such a multisystemic syndrome is detected, appropriate follow-up care is provided as with hereditary kidney cancer families.

It is suspected that hereditary kidney cancer is underdiagnosed. Identifying the families with increased risk for kidney cancer allows clinicians to improve the prognosis of persons with genetic cancer susceptibility. This review discussed the characteristics of inherited kidney cancer and how to improve their prognosis (**Table 5**).
