"Genetic Cancer" or "Hereditary Cancer"?

Prof. Dr. Metin Çakmakçı, the Director of the Breast Health Center, provided information on "genetic" and "hereditary" cancers...

Cancers are diseases that arise as a result of changes in one (or more) of the cells that make up our organs and tissues. These changes, which cause cancer, occur in the genes within the cell's nucleus, which determine the behavior of the cell, its multiplication methods, and the proteins it produces. Some mutations or disorders in the genes can cause the cell to behave abnormally. Over time, the cell accumulates harmful substances it cannot manage, cannot repair itself, and eventually begins to malfunction.

Some of the defective cells, whose genetic structure has been irreparably damaged and often at multiple points or stages, transform into cancer cells. The cause of all cancers is genetic. The damage in the genetic codes can result from harmful environmental effects such as chemicals, radiation, hormones, viruses, diet, or even the natural aging of the cell.

Cancer cells (a) begin to multiply uncontrollably, at a rate faster than normal; (b) while multiplying, they may invade healthy neighboring tissues; (c) they can detach from the tissue they originated in and spread to other tissues through the bloodstream or lymphatic system, where they can attach, settle, and continue multiplying. The masses they form as they multiply are the tumors we diagnose as cancer, and when they multiply in a distant site, they form secondary tumors, which we call metastases.

All cancer cells have harmful genetic mutations, and typically, there is more than one mutation. The stages from the genetic mutations within the cell to the emergence of the tumor generally develop more slowly than expected, usually over years.

The harmful genetic changes in the cell’s nucleus accumulate over time and ultimately transform the cell into a cancerous one. Most cancers develop this way, starting with one or a few cells, and the disease is usually seen in older ages.

In Hereditary Cancers, the Baby is Born with Mutated Genes

In some cases, harmful genetic mutations that can cause cancer are passed from the mother or father to the newborn baby. The child is born with this mutation, and as they grow older, cancer may develop in some of these individuals. These are referred to as "hereditary cancers." This is different from cancers that develop due to mutations that occur in the individual over time, which are also "genetic." It is more accurate to call cancers that are not hereditary and make up about 80-90% of cancers, "sporadic cancers."

The likelihood of a parent with a harmful gene that causes cancer (whether they have cancer or not) passing on this defective gene to their child is 50%.

Differences in Hereditary Cancers

Cancer is a common disease. Therefore, multiple family members may have cancer, but this alone does not necessarily mean the cancer is hereditary. However, it is significant if the same type of cancer (or cancers that we know arise from the same genetic defect, such as breast and ovarian cancers) appears in multiple generations of a family or in multiple relatives of the same generation.

Additionally, hereditary cancers—unlike their sporadic counterparts—are usually diagnosed at younger ages, may be more aggressive, and may have different appearances under the microscope. Their response to treatment may also differ, and they may show different sensitivities to certain medications.

Known Genetic Mutations That Cause Cancer and the Cancers They Lead To

Our knowledge on this subject has increased over the years. The most well-known mutations are likely the BRCA1 and BRCA2 gene mutations. However, mutations in other genes such as PALB2, ATM, CHEK2, PTEN, TP53, CDH1, STK11, NF1, MLH1, MSH2, MSH6, PMS2, EPCAM, and BRIP1 are also known, with more being identified every day. We know of hundreds of different cancer-causing mutations in the BRCA1 or BRCA2 genes alone, meaning this issue is more complex than previously thought.

Children who inherit these mutated genes from their parents have a much higher-than-average risk of developing cancer in later years.

Why Genetic Testing Is Not Done on Everyone

The analysis of the genetic code within cells and the identification of abnormal genes is a complex, time-consuming process that can only be done in specialized laboratories and is ultimately an expensive test. With today's medical technology and given the very low likelihood of meaningful results, these analyses are not routinely performed on all cancer patients or their relatives.

However, in certain cases, genetic testing should be conducted, such as in the following situations for a patient with breast cancer:

• If the patient is under 45 years old at the time of diagnosis,
• If cancer is present in both breasts,
• If there is a history of breast, ovarian, pancreatic, or prostate cancer in close relatives,
• If the cancer is of the "triple-negative" subtype,
• If the patient or a relative with breast cancer has male breast cancer.

Breast Cancer Example

1. Approximately 10% of all breast cancers are hereditary, while 90% are sporadic. This means we must accept that one in ten cancer patients has inherited a defective gene from their parents. Although the mutation can occur in any gene, the problem is most likely to occur in the BRCA1 or BRCA2 genes. In cases where the likelihood of heredity is high (as outlined above), extended genetic panels that test for these two genes, as well as others, should be used if possible.
2. The mutation can be inherited from either parent. A common mistake is to only investigate the maternal side, such as the mother or aunt.
3. Most breast cancer cases are sporadic, meaning there is no family history. The belief that "there is no cancer in my family, so I won’t get it" is incorrect.
4. Individuals with a significant mutation in the BRCA genes have a 55-85% chance of developing breast cancer. Therefore, individuals known to carry these mutations should have regular breast exams every six months after age 25, annual breast MRIs after this age, and annual mammograms after age 30.
5. Since no genetic treatment exists today to prevent breast cancer, individuals at high risk should discuss and consider bilateral mastectomy (surgical removal of both breasts) with reconstruction using prosthetics.
6. When surgery is not desired, hormone therapies should be considered, even though they do not eliminate the risk, they can reduce it.
7. Due to the high risk of ovarian cancer, after age 30, gynecological exams and, for those with BRCA1 mutations, surgical removal of the ovaries and fallopian tubes should be considered around ages 35-40, and for those with BRCA2 mutations, around ages 40-45.
8. Changes in diet or lifestyle have not been shown to provide any benefit in reducing cancer risk.