Chapter 21 Aetiology and epidemiology of neoplasia
Many things contribute to the development of neoplasia, producing a combination of factors that may or may not be under individuals’ control (Table 3.21.1). The common theme among these factors is that they result in the accumulation of genetic mutations (see Ch. 22) and defects in the control of cellular proliferation.
|Inherited genetic defects||Familial adenomatous polyposis||Colorectal cancer|
|Exposure to chemical carcinogens||Cigarette smoking||Lung cancer|
|Infection with certain microorganisms||Human papillomavirus||Cervical cancer|
|Exposure to forms of radiation||Chernobyl victims||Thyroid cancer|
Genetic abnormalities are very commonly identifiable within neoplastic cells but many of these have occurred after the initiation of neoplasia, within stem cells that possessed a normal genetic constitution and without further cases of the same neoplasm occurring within the same family. However, many neoplasms occur at increased frequency within particular families. In a minority of cases, neoplasia occurs within a family owing to an inherited mutation within a single gene (see also Table 3.22.1):
However, the majority of neoplasms occurring more commonly within affected families arises without a familial pattern suggestive of an inherited defect within a single gene. The genetic basis for this observation is not fully understood but it is likely that a combination of mutations within several ‘low penetrance’ genes accounts for this increased cancer incidence. Colorectal cancer is a good example of familial clustering, with around 25% of cases occurring in families with more than one further case but without evidence of conditions such as familial adenomatous polyposisor hereditary non-polyposis colorectal cancer.