This population based case-control study has confirmed that a family history among first degree relatives is an important risk factor for prostate cancer, and suggests that service in the Vietnam war is also a risk factor for prostate cancer (although this finding did not reach statistical significance).
The role of family history is one of the few factors that do have a consistent positive association with prostate cancer [5]. Almost universally studies using different study designs including hospital based and population based case-control, cross sectional, family and cohort studies have found that a family history of prostate cancer in a first degree relative is associated with at least a doubling of risk among relatives [6–11] similar to our finding.
Several limitations of our data on family history are acknowledged. Firstly, family history data was collected by self reports which were not verified. However self report of prostate cancer in first degree relatives has been shown to be relatively accurate [5, 6]. Selection bias may also have occurred if controls with a family history of prostate cancer were more likely to participate in the case-control study. Recall bias may also have occurred, as cases may differentially report their family history compared with healthy controls.
In addition, the level of screening in the Australian population is an area of interest to note. In the early 1990s the incidence of prostate cancer dramatically increased after the introduction of widespread use of prostate-specific antigen (PSA) testing became fashionable in Australia [12–14]. These increases may have had an affect on the reporting of family history of prostate cancer [14].
Our analysis suggests a doubling of prostate cancer risk among Vietnam War veterans. However this result was not statistically significant and was based on small numbers of Vietnam veterans (n = 34). These results are consistent with the findings of the Australian veterans study [2] which validated veterans self-report of prostate cancer with the national cancer registry. It found 212 confirmed cases of prostate cancer as compared with 147 expected cases [2], which equates to a standardized incidence ratio of 144. One proposed causative factor for the increase in prostate cancer is exposure to herbicides from a US operation known as 'Ranch Hand'. Nearly 19 million gallons of herbicide were sprayed on approximately 3.6 million acres of Vietnamese land [15]. Spraying began in 1962, intensified in 1967 and was believed to be stopped in 1971 [16]. During the operation a variety of herbicide formulations were used, however most were mixtures of phenoxy herbicides, 2,4-dichlorophenoxyacteic acid (2,4-d) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) [15, 17]. This herbicide was shipped out in drums with orange stripes, and so it was called Agent Orange [15].
The Center for Disease Control (CDC) proposed three efforts to assess the health of Vietnam veterans in the 1980's including a historical cohort study that compared 9324 Vietnam Army veterans with 8989 Vietnam-era Army veterans that served elsewhere [18] and a related population based case-control study using incident cases from eight cancer registries [15]. However, the overall numbers of subjects in these studies with substantial herbicide exposure were too small to support firm conclusions [15, 18, 19].
In a cohort of Australian national service conscripts, cause of death classes for deaths among 19 205 veterans of the Vietnam conflict were compared to 25 677 veterans who only served in Australia. Of 260 deaths, thirty three were due to neoplasms [20]. There was no statistically significant difference between the two groups in death rates from neoplasms, nor were deaths from specific neoplasms more frequent among the group that served in Vietnam [20]. However this study was limited by the relatively brief follow-up period and the young age of the Vietnam veteran population and a follow-up study at a more relevant time was recommended [15, 17, 20]. Most of our subjects were in over 55 and thus are in the age-groups of most interest for any cancers that may have been induced by exposure in Vietnam [21].
One of the challenges in assessing the health outcomes of the Vietnam conflict is quantifying the exposure. There is little precise information about how much exposure or even what herbicides any individual was exposed to and no standardised methods are available for estimating the extent of the exposure on an individual level [15, 22, 23]. Other combat exposures such as infectious diseases and stress are also difficult to measure [22].
Of the veterans in our study that served in Vietnam, most were army personnel. The literature suggests that members of the US Army Chemical Corps, who stored and mixed herbicides are thought to have had the heaviest exposures; members of the Special Forces units who defoliated remote campsites; and members of Navy river units may also have had heavy exposures [15, 22]. Australian troops tended to be confined to the Phoc Tuy Province which was not heavily sprayed [24].
Because of the limitations of the Vietnam veteran studies, indirect sources provide an important secondary source on the potential carcinogenicity of Agent Orange exposure. These include studies on Vietnamese soldiers exposed to the same herbicides; occupationally exposed workers in a variety of settings; people exposed after industrial accidents. On review of this literature, Frumkin (2003) suggested the evidence of an association between Agent Orange and prostate cancer is not strong.
In Australia the Department of Veterans Affairs (DVA) is responsible for providing health care to Australian veterans, including veterans who served in Vietnam [25]. Prior to the mid 1990's Australian Vietnam veterans received most of their health care in hospitals that were government owned and operated [26]. The veterans' health scheme now funds, rather than provides directly treatment by general practitioners, specialists, hospitals and allied health providers [25]. Some co-payments are required for high end dental and optical treatment [25]. Essentially veterans have access to health services that represent the best mix for an individuals' circumstance. Veteran status should not represent any distinct access or financial advantage over the general population in Australia who have access to a health care system which is a public-private mix.[25]
Strengths of our study include the use of a population-based cancer registry and pathologically-confirmed cases of prostate cancer. Further, the military history data we collected were detailed and not the sole focus of the self-administered questionnaire. The accuracy of self reported combat exposure and deployment in an area of conflict has been reported to be consistent amongst men who have held a tactical military occupational specialty, amongst those assigned to combat units and amongst those who served in Vietnam [22].
A limitation of this study was the low response from eligible participants. Only 64% of the eligible cases and 43% of eligible controls agreed to participate in this study. However, this response rate for controls is consistent with other recently conducted studies of Australian men and prostate cancer [12, 27, 28]. There did not appear to be major biases in the selection of cases, but we were unable to examine selection bias in the selection of controls.
