Tumors with familial occurrence

General information
Most human cancers occur sporadically. Their frequency in the family corresponds to the so-called population risk.

In the case of malignant transformation, it is caused only by somatic mutations, benign tumors represent a lower risk and tend to be surgically removed. Both Proto-oncogenes and tumor suppressor genes or mutator genes can be mutated in tumor tissue.

If a mutated tumor suppressor gene or a mutator gene is transferred by the germ cell of one of the parents and the mutation of the other allele  occurs in the somatic cell, then we speak of a familial occurrence. Predisposition to a certain type of cancer is usually inherited. Approximately 10-15% of tumors are inherited; then the frequency of occurrence of a certain type of tumor in the family or pedigree is higher than its incidence in the population.

Typically, these are mainly mutations in tumor suppressor genes. These mutations have a recessive character, so to completely eliminate the tumor suppressor gene, it is necessary to exclude (mutations) both alleles of this gene (Knudson's theory of two interventions). However, from the point of view of clinical genetics, these hereditary tumor syndromes are inherited autosomal dominantly (albeit with incomplete penetration). This is due to the fact that a congenital (germline) mutation of the relevant tumor suppressor gene is a significant risk for the development of the relevant disease, which thus develops in the vast majority of people with the relevant germline mutation

The familial occurrence of tumors is characterized by:


 * affecting several family members with the same type of tumor;;
 * earlier onset of the disease compared to the same type of tumor occurring sporadically;
 * multifocal or bilateral occurrence;
 * the emergence of one, two, sometimes even several primary tumors of different organs in the same individual (generally - tumor multiplicity).

Sporadic tumors

 * most human cancers are random in the population - sporadic - meaning that gene mutations have only occurred in somatic cells
 * the frequency of cancer in the family then corresponds to the population risk
 * approximately every third citizen in our country will develop some form of cancer - most often colorectal cancers and prostate tumors in men, breast cancers in women
 * protooncogenes, tumor suppressor genes and mutator genes can be mutated in tumor combinations in various combinations
 * Mutations in specific genes - marker genes - are known for some types of tumors

The same type of cancer that occurs sporadically can have hereditary and familial occurrences (eg some tumors of the lung, breast, colon, melanoma, etc.).

Familial occurrence of tumors

 * a higher incidence of tumors of a similar type in more family members is defined as a familial incidence of cancer when the genetic cause (mutation) is unknown
 * in the familial occurrence of a certain type of tumor, the cause of the same type of tumor may be due to the same environmental factors as dietary habits (colon), high incidence of certain viral diseases (liver tumors - hepatitis B virus, etc.)

Hereditary tumor incidence

 * if the mutated gene is transferred by the germ cell of one of the parents (germline mutation) and the mutation of the other allele occurs in the somatic cell, we speak of a hereditary occurrence of the tumor
 * germline mutation transfer in most cases involves tumor suppressor genes or mutator genes
 * germline mutations of two proto-oncogenes are currently known
 * inheriting a germline mutation predisposes to a particular cancer
 * an inherited character exists in approximately 5-10% of cancers
 * in this case, the frequency of occurrence of a certain type of tumor in the family is higher than its incidence in the population
 * from the point of view of formal genetics, the occurrence of hereditary predisposed tumors appears as heredity typically autosomal dominant with incomplete penetration
 * hereditary occurrence is characterized by involvement of several family members with the same type of tumor or a certain group of cancers (eg Lynch syndrome) and earlier onset of the disease compared to the same type of tumor occurring sporadically
 * the incidence of the tumor is mostly multifocal or bilateral (bilateral acoustic neurinoma, multifocal and bilateral retinoblastoma, bilateral breast tumor)
 * in some cases, one, two, and sometimes several primary tumors of different organs develop in the same individual
 * in these families, the occurrence of one type of cancer may indicate a risk of cancer in another organ

- osteosarcomas, fibrosarcomas, melanomas occur in patients with hereditary retinoblastoma

- Ovarian tumors or small cell lung tumors also occur in predisposed individuals in patients with hereditary breast cancer

Neurofibromatóza
There are neurofibromatoses I and II. type. The disease affects the PNS, tumors - neurofibromas - are benign, but some patients have an increased incidence of malignant tumors of other organ systems. An example is acoustic neurinoma (typical of type II neurofibromatosis). Their formation is conditioned by mutations in the chromosomal region: 17q11 ( NF1 gene) and 22q12 ( NF2 gene).

Li-Fraumeni syndrome
It is characterized by the occurrence of various types of hereditary primary tumors. Their formation is conditioned by a mutation in the tumor suppressor gene TP53 (17p13.1).

Hereditary breast and ovarian cancer
It is caused by a mutation in the tumor suppressor gene BRCA1 (17q21) nebo BRCA2 (13q12). The cancer may be related to mutations in other genes (eg TP53, PALB2 , CHEK2 , RAD51 , PTEN , STK11 , etc.).


 * Breast cancer is the most common malignancy in women
 * both sporadic and hereditary forms are formed by a multi-step process that involves activation of oncogenes and inactivation of tumor suppressor genes
 * aneuploidy and amplification of some genes (HER2 / neu) is observed during karyological examination
 * inactivation of tumor suppressor genes is often caused by point mutations in the gene on paired chromosomes or deletions of the gene / part of the gene
 * in hereditary types of breast or breast and ovarian tumors, 2 tumor suppressor genes are used for diagnosis - BRCA1 and BRCA2 (breast cancer ½)
 * BRCA 1 gene mutation is the cause of 52% of hereditary diseases
 * BRCA 2 gene mutation is the cause of 32%
 * 16% of patients with hereditary breast cancer have an inherited syndrome caused by mutations in other genes


 * the products of both BRCA genes are involved in the maturation of the mammary gland and form complexes with the products of other genes, thus participating in the course of the cell cycle and in the repair of double-stranded DNA breaks
 * BRCA1 inherited mutation occurs in women in families with familial breast, ovarian or breast and ovarian cancer

Familial adenomatous polyposis
It is caused by a mutation in the tumor suppressor gene APC (5q21-22), a rarer variant is caused by a mutation in the mutator gene MUTYH (1p32-34).


 * Colorectal polyposis with the development of colorectal cancer.

Hereditary nonpolyposis colorectal cancer - Lynch Syndrome I and II
It is caused by mutations in various mutator genes (eg. MSH2, MLH1, PMS1, PMS2).


 * Colorectal cancer without previous polyposis (HNPCC).

Peutz–Jeghers syndrome
Caused by a mutation in the STK11 gene.


 * Colon polyposis associated with typical pigmentations (not only) in the oral cavity.

Wilms' tumor
Caused by a mutation in the WT1 (11q13) gene.

Familial retinoblastoma
Caused by a mutation in the tumor suppressor gene RB1 (13q14).

Familial malignant melanoma
Caused by a mutation in the tumor suppressor gene MLM (9q21).

Further examples of disease familial occurrence

 * Stomach tumor;
 * Bladder Cancer;
 * Cervical cancer;
 * Lung tumor.

Related Articles

 * Proto-oncogenes
 * Tumor suppressor genesmutator genes
 * Mutator genes, genome stability
 * Incidence of Tumors


 * Neurofibromatosis
 * Wilms' tumor


 * Ataxia telangiectasia‎
 * Bloom syndrome
 * Fanconi anemia