http://ebooksmedicine.net alcohol and tobacco smoking synergistically increase the risk for developing cancers of the upper airways and upper digestive tract.
Reproductive history. There is strong evidence that lifelong cumulative exposure to estrogen stimulation, particularly if unopposed by progesterone, increases the risk for developing cancers of the endometrium and breast, both of which are estrogen-responsive tissues.
Infectious agents. It is estimated that infectious agents cause approximately 15% of cancers worldwide.
Thus, there is no escape: it seems that everything people do to earn a livelihood, to subsist, or to enjoy life turns out to be illegal, immoral, or fattening, or—most disturbing— possibly carcinogenic!
In general, the frequency of cancer increases with age. Most cancer deaths occur between 55 and 75 years of age; the rate declines, along with the population base, after 75 years of age. The rising incidence with age may be explained by the accumulation of somatic mutations that drive the emergence of malignant neoplasms (discussed later). The decline in immune competence that accompanies aging also may be a factor.
Although cancer preferentially affects older adults, it also is responsible for slightly more than 10% of all deaths among children younger than 15 years of age (Chapter 7). The major lethal cancers in children are leukemias, tumors of the central nervous system, lymphomas, and soft-tissue and bone sarcomas. As discussed later, study of several childhood tumors, such as retinoblastoma, has provided fundamental insights into the pathogenesis of malignant transformation.
Acquired conditions that predispose to cancer include disorders associated with chronic inflammation, immunodeficiency states, and precursor lesions. Many chronic inflammatory conditions create a fertile “soil” for the development of malignant tumors (
Table 6.3 ). Tumors arising in the context of chronic inflammation are mostly carcinomas, but also include mesothelioma and several kinds of lymphoma. By contrast, immunodeficiency states mainly predispose to virus-induced cancers, including specific types of lymphoma and carcinoma and some sarcoma-like proliferations.
Precursor lesions are localized disturbances of epithelial differentiation that are associated with an elevated risk for developing carcinoma. They may arise secondary to chronic inflammation or hormonal disturbances (in endocrine-sensitive tissues), or may occur spontaneously. Molecular analyses have shown that precursor lesions often possess some of the genetic lesions found in their associated cancers (discussed later). However, progression to cancer is not inevitable, and it is important to recognize precursor lesions because their removal or reversal lowers cancer risk.
Many different precursor lesions have been described; among the most common are the following:
Table 6.3 Chronic Inflammatory States and Cancer
PancreatitisPancreaticcarcinomaAlcoholism,germlinemutations(e.g.,inthetrypsinogengene)
ChroniccholecystitisGallbladdercancerBileacids,bacteria,gallbladderstones
Refluxesophagitis,EsophagealGastricacidBarrettesophaguscarcinoma
Sjögrensyndrome,MALTlymphomaHashimotothyroiditis
Gastritis/ulcersGastricHelicobacter pylori adenocarcinoma,MALTlymphoma
AdaptedfromTlstyTD,CoussensLM:Tumorstromaandregulationofcancerdevelopment,Ann Rev Pathol Mech Dis 1:119,2006.
Squamous metaplasia and dysplasia of bronchial mucosa, seen in in habitual smokers—a risk factor for lung carcinoma (Chapter 13)
Endometrial hyperplasia and dysplasia, seen in women with unopposed estrogenic stimulation—a risk factor for endometrial carcinoma (Chapter 19)