cancer syndromes

Chapter 33 Inherited cancer syndromes

Normal human development and the development of disease states are both reliant upon a combination of an individual’s genetic composition (nature) and factors within the environment in which the individual exists (nurture). Variations in genetic composition are, therefore, important contributors to disease development.

Genetic mutations and disease development

Neoplastic diseases are characterized by the presence of genetic mutations within the neoplastic tissue (Fig. 3.33.1), which are often multiple in nature and which are associated with loss of the normal mechanisms controlling cellular growth and maturation (Ch. 22). In the majority of cases, cells within the affected individual’s non-neoplastic tissue do not usually contain demonstrable genetic mutations (i.e. they appear genetically normal).

Inherited predisposition to neoplastic disease

Inherited cancer syndromes are characterized by the presence of a mutation that is inherited from one or both parents and which leads to a significantly increased risk of development of a particular neoplasm or group of neoplasms. This is reflected in an increased incidence of neoplasia within affected families, usually with an identifiable Mendelian pattern of inheritance in a dominant fashion (Table 3.33.1). Inherited mutations associated with familial cancer syndromes are usually present within genes important in the regulation of cellular growth and/or maturation and are commonly termed tumour suppressor genes (Ch. 22). Neoplasms develop when mutation or loss of the second normal copy of the gene occurs such that the tumour tissue then contains no normal copies of the gene.


Syndrome Gene Clinical manifestation
Familial adenomatous polyposis APC (adenomatous polyposis coli) Multiple adenomas in colon and small intestine; colorectal cancer at very young age
Hereditary non-polyposis colorectal cancer hMLH-1, hMSH-2, hMSH-6, PMS-1, PMS-2 Colorectal cancer at young age (especially < 50 years); endometrial carcinoma
Familial breast cancer BRCA-1, BRCA-2 Breast carcinoma at young age (e.g. 20–40 years), may be bilateral; ovarian carcinoma
Multiple endocrine neoplasia (MEN) 1 and 2 MEN Adenomas within endocrine glands; medullary thyroid carcinoma (in MEN 2)
Familial retinoblastoma RB1 Retinoblastoma at young age, often bilateral
Li-Fraumeni syndrome p53 Multiple neoplasms, especially soft tissue sarcomas

Neoplasms occurring within inherited syndromes usually also occur sporadically (i.e. within individuals who have not inherited a genetic mutation) but with different clinicopathological features. For example, neoplasms occurring within an inherited syndrome usually develop at an earlier age and are more commonly multiple. These conditions may be associated with additional non-neoplastic clinical features e.g. familial adenomatous polyposis (Fig. 3.33.2) is associated with abnormal retinal pigmentation termed Roth spots.

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Jul 3, 2016 | Posted by in MUSCULOSKELETAL MEDICINE | Comments Off on cancer syndromes
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