Genetic testing of hereditary cancer

The number of people suffering from cancer is growing every year in Latvia and in the world. Depending on the localization, the inherited tumors are diagnosed in 5-30% of cancer patients. Since the family history is not always complete, the assumption of the hereditary tumor should be based on tumor histology or suspicion of the hereditary cancer.

Timely molecular genetic testing allows you to determine the disease, predict its process and choose treatment tactics. Using this testing, it is possible to protect not only yourself, but also your family, because, having found changes in the genes that increase the risk of cancer, even before it develops, it is possible to make timely risk assessment and choose the right diagnosis or risk reduction option. If the changes that increases the risk of oncology are detected in any your gene, it is recommended to inform your relatives who may also be carriers of these changes, since they also need to check for the changes to determine whether they are at increased risk. The molecular genetic testing of minors for ethical reasons is carried out only in cases of certain hereditary tumor syndromes where tumor development is possible before reaching adulthood.

One of the most known and described hereditary tumors is hereditary breast cancer and ovarian cancer. Hereditary cases of breast cancer and ovarian cancer account for about 20-30% of all cases of breast cancer. 40-50% of them are associated with changes in the BRCA1 and BRCA2 genes. According to various studies, the frequency of clinically significant variants of the BRCA1 and BRCA2 genes is 5-10% in patients with breast cancer, with more changes observed in patients under the age of 40 years. There are several allelic variants of BRCA1 and BRCA2 in Latvia, found in patients with breast cancer, who have a family history of cancer, or with an unclear family history of cancer. These variants are found not only in Latvia, but also in the world. One of them, the unique variant in the BRCA2 gene was found only in the Latvian population. Determination of allelic variants of BRCA1 and BRCA2 may be important not only for choosing the right treatment tactics, but also for determining the risks of the disease for the patient’s family members. It is possible to choose the right tactics for the timely diagnosis of the disease or even avoid it knowing these risks.

In the case of oncological diseases of various localizations, a similar picture is observed, as in the cases of hereditary breast / ovarian cancer. Up to 30% of cancer patients may have changes in the genes responsible for tumor development. Timely genetic risk awareness makes it possible not only to diagnose the disease at an initial stage when the treatment is more successful, but also, depending on hereditary tumor syndrome, to choose preventive surgery, if possible, and to avoid the disease or significantly reduce the risk of oncological diseases.

In which cases molecular genetic testing of hereditary tumors would be required:

• The diagnosis of oncology at an early age;
• Tumors of various localizations in the same patient;
• Multiple primary tumors, especially of one localization (for example, breast or colorectal), in the same patient;
• Several close relatives with the same localization oncology (for example, mother, daughter and sister with breast cancer; father and son with colorectal cancer);
• An unusual tumor manifestation (for example, breast cancer in man);
• Congenital malformations associated with hereditary tumor syndromes (for example, benign skin lesions).

Cancer types that may indicate hereditary tumor syndrome:

• Triple-negative breast cancer (suspected hereditary breast cancer caused by changes in the BRCA1 or BRCA2 genes);
• Epithelial ovarian cancer, fallopian tubes or peritoneal cancer, especially serous histology (suspected hereditary breast / ovarian cancer caused by changes in the BRCA1 or BRCA2 genes);
• Colorectal cancer with confirmed DNA mismatch repair deficiency – microsatellite instability (suspicion of Lynch syndrome);
• Endometrial cancer with confirmed DNA mismatch repair deficiency – microsatellite instability (suspected Lynch syndrome)

If you have observed one of these criteria in your family, but the cancer has not yet developed, even in this case you can make molecular genetic testing. The most optimal type of testing is to carry out molecular genetic testing for a patient who has already been diagnosed with cancer, and in the case of positive result, to carry out family cascade testing for specific changes.

iVF Riga Genetic Centre provides patients with the opportunity to carry out genetic tests both to predict the inheritance of a specific cancer and to exclude most common mutations in completely healthy people.

Genetic consultations are also available at the iVF Riga Genetic Centre after testing, if additional questions arise about the risks of developing hereditary tumors and genetic counseling of the family is required.

We offer tests to be performed quickly to determine the diagnosis and risk of the disease as soon as possible. Early cancer diagnosis is very important to improve treatment outcomes and quality of life.

The main testing method is based on a sequence detection approach, including new generation sequencing, which allows to detect changes in genes accurately and with a high degree of confidence.

Genetic centre iVF Riga offers to determine the probability of hereditary cancer.

• Determination of BRCA1 and BRCA2 hereditary mutations

This testing includes the most common allelic variants of BRCA1 and BRCA2 genes and allows to diagnose the majority of patients with hereditary breast and ovarian cancer. However, this analysis examines only a small part of the BRCA1 and BRCA2 genes and does not exclude the presence of other genetic changes that can cause tumor development.

• Most common hereditary tumors panel – 31 gene sequencing with NGS (Next-Generation Sequencing)

Detects changes in 31 genes associated with hereditary tumor syndromes. The advantage of this panel is its wide diagnostic capabilities, which, when suspected of hereditary tumor syndromes, can not only determine changes in certain syndrome-related genes, but also expand the range of tested genes, including genes, whose changes can occur phenotypically as tumors less typical for the syndrome. This panel is recommended for hereditary breast / ovarian cancer, as well as in the case of various other tumors, such as Lynch syndrome, or hereditary nonpolyposis colorectal cancer, Li-Fraumeni syndrome, Cowden syndrome, Multiple endocrine neoplasia (MEN), various kinds of hereditary intestinal polyposis with high risk of malignancies, Neurofibromatosis type 1 (NF1). In terms of cost-benefit, the analysis is comparable to the complete single gene sequencing, while the information obtained is much broader and more comprehensive.

• 111 different genes sequencing using NGS

Determines changes in 111 different genes associated with hereditary tumor syndromes. This panel is most widely used since it includes not only genes of the most common hereditary tumor syndromes, but also more rare autosomal recessive genes, whose changes may occur more rarely, but at an earlier age.
Panel is used for molecular genetic confirmation of various hereditary tumors, as well as extended diagnosis of hereditary breast/ovarian cancer. Includes genes whose changes are associated with an increased risk of developing hereditary breast / ovarian cancer, intestinal polyposis and colorectal cancer, malignant anemia, hereditary endocrine tumors, etc.

• Family cascade testing

In case of a positive result, Family cascade testing is particularly important to identify patients in a high-risk group. A medical geneticist’s consultation is initially needed, during which a family tree is examined and risks are assessed for each family member. Based on the information obtained, a plan is individually made for the Family cascade testing. The molecular genetic testing of minors for ethical reasons is carried out only in cases of certain hereditary tumor syndromes where tumor development is possible before reaching adulthood.

Your doctor will determine the best testing variant for you, or you can also consult a qualified specialist here in the clinic iVF Riga.

Carrying out any testing in our clinic, you get not only an incomprehensible combination of letters and numbers, but also an explanation, what means each of the detected clinically significant or possible clinical changes, as well as a full interpretation for each of these options. An experienced and reliable team of geneticists works in our clinic; our genetic laboratory is equipped with the latest technological achievements in the field of molecular genetics. Clinic iVF Riga also offers consultations with a geneticist who, in case of a positive answer, will explain what risks exist for close relatives, how to assess these risks and how to proceed.
It is possible to preserve own genetic material (eggs, ovarian tissues, semen) in our clinic if oncotherapy is required (some types of oncotherapy may harm germ cells, excluding the possibility of creating offspring in the future).
As an option for family planning, if hereditary tumor syndrome with a specific mutation is confirmed, it is possible to apply PGT-M, or preimplantation genetic testing for monogenic diseases, to give birth to a child not at increased risk of developing tumors. It would be particularly important for hereditary tumor syndromes, where cancer develops early and with 100% penetrance.