Most countries with adequate statistical infrastructure have registered declines in gastric cancer mortality and incidence rates. Such a trend is dominated by the most frequent variant, namely the so-called intestinal type of adenocarcinoma, usually ulcerated and occupying predominantly the antrum and the antrum-corpus junction. This variant is considered the endstage of a prolonged precancerous process with gradual progression from (a) chronic active gastritis to (b) multifocal atrophic gastritis to (c) intestinal metaplasia, first resembling the phenotype of the small intestine and later that of the colon, to (d) dysplasia and (e) finally to invasive carcinoma. Major trends in dietary habits, namely lower intake of salt and increased and more frequent consumption of fresh fruits and vegetables, have been linked to the decline. In parallel with those trends, improved sanitation and more adequate housing may be responsible for the declining rates of infection with Helicobacter pylori, the major cause of chronic active gastritis. A decline in the frequency of papillary adenocarcinoma of the oxyntic mucosa, associated with the pernicious anaemia syndrome, appears to have taken place much earlier. Although the frequency of the pernicious anaemia syndrome seems to have remained at similar levels, its complications in terms of papillary adenocarcinoma have decreased in populations of northern European extraction. This may be related to time trends in dietary habits. The secular decline in diffuse carcinoma has been either of much less magnitude or non-existent. Few clues are available on this tumour variant. It is somewhat predominant in women, in subjects of blood group A phenotype, and less frequent in older subjects. Cell lines derived from diffuse carcinomas lack functional calcium dependent adhesion molecules ("cadherins"). Recent increases in incidence rates have been registered for adenocarcinoma of the gastric cardia. This increase parallels that of lower oesophageal adenocarcinoma, frequently linked with Barrett's oesophagus, reflux oesophagitis, a history of duodenal ulcer and gastric hypersecretion. New developments in molecular biology are being used to study the process of gastric carcinogenesis. There is hope that specific molecular alterations may provide better understanding of the different variants of gastric carcinoma and their secular trends.
Kaposi's sarcoma-associated herpesvirus, also known as human herpesvirus 8, is a new gamma-herpesvirus present in all forms of Kaposi's sarcoma and in primary effusion lymphomas. Molecular epidemiological studies suggest that Kaposi's sarcoma-associated herpesvirus is confined to the risk groups developing Kaposi's sarcoma; however, some have reported a more widespread distribution. First-generation serological assays suggest that this new virus is not ubiquitous and is predominantly sexually acquired. The viral genome encodes various proteins which could play a role in the pathogenesis of Kaposi's sarcoma or lymphomas, including cyclin D and bcl-2 homologues, as well as the chemokines interleukin-8, macrophage inflammatory protein, an interferon regulatory factor, an interleukin-8 receptor and a neural cell adhesion molecule-like protein.
The global health burden of infection associated cancers hepatitis B virus and liver cancer - unanswered questions human papillomavirus and cancer - the viral transforming genes HPV and cancer Epstein-Barr virus and lymphomas nasopharyngeal carcinoma - an epidemiological approach to carcinogenesis Kaposi's sarcoma-associated herpesvirus human T-cell leukaemia virus type I (HTLV-I) hepatitis C virus human immunodeficiency virus infection and cancer is helicobacter pylori infection a cause of gastric neoplasia? schistosomes and human cancer liver flukes and liver cancer vaccination against infectious agents associated with human cancer.
Several infectious agents are considered to be causes of cancer in humans. The fraction of the different types of cancer, and of all cancers worldwide and in different regions, has been estimated using several methods; primarily by reviewing the evidence for the strength of the association (relative risk) and the prevalence of infection in different world areas. The estimated total of infection-attributable cancer in the year 2002 is 1.9 million cases, or 17.8% of the global cancer burden. The principal agents are the bacterium Helicobacter pylori (5.5% of all cancer), the human papilloma viruses (5.2%), the hepatitis B and C viruses (4.9%), Epstein-Barr virus (1%), human immunodeficiency virus (HIV) together with the human herpes virus 8 (0.9%). Relatively less important causes of cancer are the schistosomes (0.1%), human T-cell lymphotropic virus type I (0.03%) and the liver flukes (0.02%). There would be 26.3% fewer cancers in developing countries (1.5 million cases per year) and 7.7% in developed countries (390,000 cases) if these infectious diseases were prevented. The attributable fraction at the specific sites varies from 100% of cervix cancers attributable to the papilloma viruses to a tiny proportion (0.4%) of liver cancers (worldwide) caused by liver flukes.
A large number of potential molecular markers of bladder cancer have been identified, although only a few are truly independent prognostic factors. A number of markers may need to be measured in a single tumour and used as a combination for use in the diagnosis and prognosis of transitional cell carcinoma (TCC). Epidermal growth factor receptor immunoreactivity has been shown to be an independent predictor of survival and stage progression. TP53 may be an independent predictor of recurrence and overall survival in TCC confined to the bladder, and TP53 alterations may predict chemosensitivity in patients who have had TCC treated by radical cystectomy. At present molecular techniques such as fluorescence in situ hybridization and the polymerase chain reaction are restricted to the laboratory, but immunohistochemical methods are available in most hospital pathology departments. There are some discrepancies and conflicting reports of the usefulness of molecular markers in different studies, and these need to be addressed in large, prospective, multi-institutional studies using standardized molecular techniques.
Bladder cancer has classically been associated with exogenous risk factors, and a large literature has identified risk factors associated with the genesis of transitional cell carcinoma. Only recently have efforts been made to identify host factors and to evaluate possible changes in tumour presentation and biology, including grade and stage, in association with these risk factors. The available literature appears to demonstrate alterations in tumour biology associated with environmental carcinogens. Various studies have suggested a consistent upgrading of bladder cancer stage and grade as a result of cigarette smoking and high risk occupational exposures. It is important, however, that all factors associated with increased risk for bladder cancer be more extensively evaluated in assessing the validity of this concept.
The evolution of the malignant phenotype requires a set of genetic and epigenetic changes in sets of genes responsible for regulation of normal growth and cell death, of "social behaviour" and differentiation. The sum of these changes, not only the sequence, determines the malignancy as well as its grade. The probability of invasiveness shows a remarkable relationship to morphological changes, which in turn prove to be accompanied by a multitude of discrete molecular perturbations. Some of these can be characterized as functional, others as inductive with respect to their participation in the process. Since only the functional changes regulate malignant behaviour per se, it is an important task for future research to assemble a set of such changes, find markers for them and combine morphological and molecular indicators to achieve prognostically optimal scores. It should be emphasized, though, that rational use of such scores using biopsy samples as a source of information cannot be defined until biopsy strategies have been standardized and optimized.
