Summary

Background

Perceived ill-health of Vietnam veterans and their families has been a public issue since 1978. Initially, the major concern was possible effects of exposure of Vietnam veterans to some herbicides (notably Agent Orange) used during the Vietnam conflict.

Two studies, of mortality among Vietnam veterans and of birth defects in their children, were commissioned by the Commonwealth Government in the early 1980s but did not find any effects attributable to the use of chemicals in Vietnam. The Royal Commission into the Use and Effects of Chemical Agents on Australian Personnel in Vietnam was established in 1983.

Dapsone was one of the chemicals reviewed by the Royal Commission. During the Vietnam conflict Australian forces had used this drug, initially for the treatment of falciparum malaria and later also for its prevention. The Royal Commission recommended studies into the carcinogenicity of dapsone. The recommendation was supported by the Hogg report, which was commissioned by the Commonwealth to coordinate its response to the findings of the Royal Commission.

The Department of Veterans' Affairs asked the Australian Institute of Health and Welfare (AIHW-then called the Australian Institute of Health) to conduct a study of cancer incidence in relation to dapsone use. A protocol, completed in November 1990, defined the study aims and design, dealing with data collection and analysis, limitations of the study, reporting, and privacy. This protocol was accepted by the Scientific Advisory Committee formed to advise the Minister for Veterans' Affairs on the study, the State and Territory cancer registries, and the AIHW Ethics Committee.

Dapsone

Dapsone (4,4'-diaminodiphenyl-sulphone) is a sulphonamide-like drug that probably acts by inhibiting folate synthesis. Folate synthesis is an essential metabolic step in those unicellular organisms that, unlike humans, cannot use preformed folates. Dapsone is used for short- and long-term treatment of leprosy and for the prevention and treatment of malaria. Adverse reactions to its use include haemolytic anaemia, methaemoglobinaemia, peripheral neuropathy, gastrointestinal symptoms, fever, pruritus and various rashes.

Despite dapsone's widespread clinical use for many years, there is little evidence that it is associated with an increased risk of cancer. There are case reports of cancers among persons who have taken dapsone, but no specific or unusual site of cancer consistently appears in these reports. None of the reports gives a biological argument for an association of specific cancers with dapsone use. Moreover, most of the patients described in these reports had leprosy and had taken dapsone at higher doses and for much longer than was the case with dapsone used prophylactically against or as treatment for malaria by Australian servicemen.

Chronic carcinogenicity studies undertaken in both rats and mice show limited evidence of carcinogenicity. Mutagenicity studies have also been equivocal.

In the absence of further data, the International Agency for Research on Cancer has been unable to determine whether dapsone should be regarded as a carcinogen of humans.

Sites of cancer of a priori interest

For dapsone exposure, the sites of cancer that have been noted in previous studies are non-Hodgkin's lymphoma, Hodgkin's disease, oral cancer, kidney cancer, bladder cancer and leukemia. Because of the earlier interest in herbicides, this study also examines cancer incidence for sites of cancer that have been hypothesised as being related to herbicide exposure: non-Hodgkin's lymphoma, Hodgkin's disease, soft tissue and other sarcoma, nasal cancer, nasopharyngeal cancer, thyroid cancer, testis cancer and primary liver cancer.

Design of this study

The aim of this study was to assess and quantify any association between cancer incidence and exposure to dapsone and to Vietnam service among Australian Army servicemen who served in Vietnam during the Vietnam conflict.

The study cohort ('servicemen') consisted of all 115,407 males who served in the Australian Army for at least one year between 1 January 1965 and 1 March 1972. Identification of servicemen, those who had been exposed to dapsone, and those treated for malaria was done through Army records. Cancer incidence was determined by reference to State and Territory cancer registry records for the period

1972 to 1989, although not all registries had complete coverage for all of this period. Cancer incidence was examined for all cancers, and for 28 sites of cancer that included the cancers of a priori interest as well as groupings with more than 30 incident cases.

Cancer incidence rates, controlling for age and calendar year, were compared for several subgroups of servicemen:

  • dapsone-exposed Vietnam veterans compared with non-exposed Vietnam veterans;
  • for dapsone-exposed Vietnam veterans, those with the higher exposures compared with those with the lower exposures;
  • Vietnam veterans with malaria compared with other Vietnam veterans;
  • Vietnam veterans compared with non-veterans;
  • dapsone-exposed Vietnam veterans compared with non-veterans;
  • servicemen compared with other males in the Australian population.

Where possible, these comparisons were made separately for National Service (conscript) and Australian Regular Army (volunteer) servicemen.

Cancer mortality was not directly assessed.