Infections and immune factors in cancer: the role of epidemiology

Abstract

An infective, mostly viral, basis has been found in an increasing number of different human cancers. In all cases, the neoplasm is a rare response to the relevant infection, which is usually present in persistent form, and requiring specific cofactors for malignancy to develop. In some cases, epidemiological evidence of infectivity preceded and promoted identification of the specific infection involved and even the discovery of the microbe itself, as in Burkitt's lymphoma and cervix cancer. In other cases, the discovery of the agent came first as in stomach and nasopharynx cancers, and epidemiology has been concerned mainly with confirming the relationship, measuring the size of the risk and identifying cofactors. Infectionlinked cancers include some of the commonest malignancies in certain large world regions, amounting to over 20% of all cancer in the developing countries. In addition to these cancers are others such as childhood leukaemia that show features indicative of an infective basis though no underlying agent has been identified. Advances in this field invite speculation about possible future discoveries and how these might be promoted. However, in that majority of cancers that are unrelated to sexual behaviour, there will be nothing even at the population level to suggest an infective basis because what is transmitted from one individual to another is not the neoplasm itself, but the underlying, often silent, infection to which the malignancy is an uncommon response. The increasing prevalence of immune impairment in human populations, as a result of the use of immunosuppressive drugs with organ transplants and the spread of HIV infection, has produced marked effects on cancer incidence in the affected groups including increases, of skin cancers, nonHodgkin's lymphoma and Kaposi's sarcoma and to a lesser extent of many other cancers, in some cases at least due to the release from immunological control of incipient infection-based malignancies.

Viral epigenomes in human tumorigenesis

“…It seems that the immune deficiency induced by HIV is responsible for tumorigenesis through the action of oncoviruses such as EBV, KSHV and HPV, which cause lymphomas, Kaposi's sarcomas and cervical carcinomas (International Collaboration on HIV and Cancer, 2000;Kinlen, 2004;Carbone and Gloghini, 2005;Carbone et al, 2007Carbone et al, , 2009Grulich et al, 2007).…”

Childhood cancer epidemiology in low‐income countries

“…13 Observations of a markedly increased incidence rate of ALL in children between 2 and 5 years old in affluent societies, the lack of such an age peak age in LIC, and occasional clustering of childhood ALL cases (especially in new towns) have fueled 2 parallel infection-based theories of leukemogenesis: the delayed-infection hypothesis 14 and the populationmixing hypothesis. 15 Both hypotheses attribute the peak incidence in industrialized countries to early infectious insulation that predisposes the immune system of susceptible individuals to aberrant or pathologic responses after subsequent or delayed exposure to common infections at an age commensurate with increased lymphoid cell proliferation. 14,15 Some other cases of childhood ALL can be attributed to maternal exposures during pregnancy, 16,17 in which risk may be modulated by genetic polymorphisms of enzyme systems responsible for the metabolism of drugs or environmental xenobiotics.…”

“…15 Both hypotheses attribute the peak incidence in industrialized countries to early infectious insulation that predisposes the immune system of susceptible individuals to aberrant or pathologic responses after subsequent or delayed exposure to common infections at an age commensurate with increased lymphoid cell proliferation. 14,15 Some other cases of childhood ALL can be attributed to maternal exposures during pregnancy, 16,17 in which risk may be modulated by genetic polymorphisms of enzyme systems responsible for the metabolism of drugs or environmental xenobiotics. [18][19][20][21] However, variations in environmental exposures and genetic susceptibility can only account for small differences in childhood leukemia incidence rates, and do not explain the large differences (up to 10-fold) between HIC and some LIC (Table 2).…”

Sequence Variants of Toll-Like Receptor 4 and Susceptibility to Prostate Cancer

“…Chronic inflammation has been associated with some cancers (e.g., cervix, breast, primary liver, and bladder cancers; ref. 16). An emerging body of evidence, including studies on sexually transmitted infections, clinical prostatitis, and genetic and circulating markers of inflammation and response to infection, supports a possible link between chronic intraprostatic inflammation and risk of prostate cancer (17).…”