**4. Genetic counseling and supporting families with hereditary cancer**

It is important to identify hereditary cancer susceptibility, because the risk of cancer, morbidity, and mortality in the mutation carriers can be reduced both in cancer patients and healthy relatives in the family. If the family mutation is known, healthy family members with mutation can participate in preventive studies. If the person does not have the known family mutation, there is no need to have follow-up care because the risk of the cancer is the same as for an average population.

Diagnostic gene testing on cancer patients is carried out in the clinical genetic units, but diagnostic genetic testing can also be ordered by a treating oncologist or surgeon for patients with kidney cancer. There are established principles for considering genetic testing in the case of suspected hereditary cancer susceptibility (**Table 6**) [43]. If there is a genetic test that is appropriate for the situation, the American Society of Clinical Oncology (ASCO) recommends access to genetic testing. Before testing the individuals, informed consent should be requested after adequate information and counseling [44]. For genetic testing the patient's peripheral blood, lymphocyte DNA is examined for identifying a possible hereditary mutation.

The investigation for finding the family mutation is always started with the affected person. A medical geneticist will determine who could have mutation with increased kidney cancer risk

The result of the gene test should be adequately interpreted

Gene testing has one of the following benefits:


**Table 6.** ASCO 2010 criteria for genetic testing.

Hereditary cancer is suspected

The ASCO has provided guidance on when genetic testing for cancer families should be considered [43]. The following three conditions should be met. If the family mutation is found, the access for healthy relatives to genetic counseling should be arranged.

in the family. If there are no surviving cancer patients in the family, with the permission of the relative, from the pathology department, a sample of the deceased person may be requested to have healthy tissue DNA for genetic examination.

Genetics of cancer is only partially known. Advanced technological methods can detect previously unknown mutations in germline and tumors. Knowledge of the biology of hereditary cancer also increases the understanding of sporadic cancers, as the same disease genes are found in hereditary and non-hereditary cancers: e.g., mutated *MET* is a driver gene in hereditary and sporadic papillary renal carcinomas [42], and mutated *WT1* is observed both in sporadic and hereditary Wilms' tumor. Novel genes and variants may be explored by whole exome (WES) or genome research (WGS), where also noncoding regions are examined, in scientific research projects. Identifying low-risk variants requires data from thousands of patients and controls, which are investigated in genome-wide association studies (GWAS).

**4. Genetic counseling and supporting families with hereditary cancer**

average population.

8 Evolving Trends in Kidney Cancer

Hereditary cancer is suspected

• Improves diagnosis

should be arranged.

The result of the gene test should be adequately interpreted

• Guides to the appropriate medical surveillance for the carriers of gene mutation • Provides information about strategies for prevention in the carriers of gene mutation

Gene testing has one of the following benefits:

**Table 6.** ASCO 2010 criteria for genetic testing.

It is important to identify hereditary cancer susceptibility, because the risk of cancer, morbidity, and mortality in the mutation carriers can be reduced both in cancer patients and healthy relatives in the family. If the family mutation is known, healthy family members with mutation can participate in preventive studies. If the person does not have the known family mutation, there is no need to have follow-up care because the risk of the cancer is the same as for an

Diagnostic gene testing on cancer patients is carried out in the clinical genetic units, but diagnostic genetic testing can also be ordered by a treating oncologist or surgeon for patients with kidney cancer. There are established principles for considering genetic testing in the case of suspected hereditary cancer susceptibility (**Table 6**) [43]. If there is a genetic test that is appropriate for the situation, the American Society of Clinical Oncology (ASCO) recommends access to genetic testing. Before testing the individuals, informed consent should be requested after adequate information and counseling [44]. For genetic testing the patient's peripheral

The investigation for finding the family mutation is always started with the affected person. A medical geneticist will determine who could have mutation with increased kidney cancer risk

The ASCO has provided guidance on when genetic testing for cancer families should be considered [43]. The following three conditions should be met. If the family mutation is found, the access for healthy relatives to genetic counseling

blood, lymphocyte DNA is examined for identifying a possible hereditary mutation.

The result of the genetic testing gives information about the cancer risk of relatives. Healthy atrisk relatives should have access to genetic counseling and predictive genetic testing after counseling if they decide (Council of Europe's The Convention on Human Rights and Biomedicine in Article 12, 1997). The clinical genetics units offer this service. The geneticist will have the opportunity to provide the laboratory with reliable information about the family mutation and arrange for the laboratory the DNA sample of the family's index patient, which is a control sample, positive control, to obtain a reliable test result. Counseling before predictive genetic testing is nondirective and includes insight of the patient and the family. In counseling, the patient and family receive not only information but also support. Increased anxiety or distress has been documented in both counselors and their families around testing when investigating hereditary VHL susceptibility [45]. The Genetic Information Nondiscrimination Act of the Council of Europe's Convention in Article 11, in 1997, was passed to prevent forms of genetic discrimination by employment and health insurance. The Council of Europe's Convention prohibits the transfer of genetic information to employers in order to prevent employment discrimination. Insurance discrimination is discussed in counseling. In Finland, genetic testing is organized by public health care, which is why very few gene tests are conducted privately.

Participation in predictive genetic testing has been studied in the Finnish Lynch syndrome families, which are at high risk for colorectal cancer and endometrial carcinoma in the uterus. Approximately 80% of the members of the family participated in genetic counseling, and 95% of them performed genetic prediction [46]. The main reasons for participating in predictive genetic testing are the potential for cancer detection in surveillance monitoring, improved treatment options in many Lynch syndrome cancer types, and improved cancer prognosis.

After the genetic testing, the counselor should always receive an interpretation of the significance of the genetic test result [43, 44]. Different mutations in the same disease gene, for example, in the inherited VHL gene, can have varying effects on cancer risk and prognosis [47]. The genetic practitioner will assess the significance of the result for each family separately. It is useful to wait until the age of 18 to allow an offspring to reach an age of consent in those inherited syndromes in which the age of onset is in adulthood. However, the early age of onset in condition like VHL could have devastating complications without early detection and management, and therefore in this syndrome predictive testing is recommended to at-risk children in family.
