UroToday.com – Testicular cancer incidence appears to be increasing worldwide. Despite growing concern over this increase, many aspects of testicular cancer epidemiology remain puzzling. So far, science provides few answers for its etiology or the geographic and temporal discrepancies in its incidence. Unfortunately, further evidence about the causal factors for testicular cancer will not be quickly forthcoming.

One reason for this lack of progress is a general problem in all cancer research, the long duration between exposure and diagnosis, often decades later. There are other more specific challenges as well: the rarity of the disease and the difficulty of obtaining unbiased reports of maternal pregnancy behavior.

The first challenge is that testicular cancer is rare and therefore limits the number of cases for analysis in any but the largest prospective studies. While the obvious solution to the problem of rare diseases is to conduct a case-control study, in the case of testicular cancer prospective data may be more important than the convenience of easily available cases.

The second challenge is the concern about asking women to report their behavior decades later, even after their child has been diagnosed with cancer. It makes sense to assume that reporting might be differentially affected by knowing a child’s cancer status. This challenge becomes even greater in the context of the known stigma over drinking during pregnancy. While this stigma serves an important purpose in encouraging pregnant women to abstain, leading to health benefits for their children, it also means that women are highly likely to underreport their actual use. While systematic underreporting is not ideal, differential reporting by case status introduces bias that cannot be overcome by having large numbers of cases.

The rarity of testicular cancer suggests that a case-control design should be used, while the concerns over bias directly contraindicate such a design. So, if case-control studies run the risk of biased exposure assessment and cohort data do not produce enough cases for definitive analysis, where does testicular cancer research go from here?

Of course public health will always benefit from the creation of new, well-designed and managed longitudinal cohort studies. Unfortunately, the cost and logistics are frequently prohibitive to produce a study with enough participants to investigate rare outcomes. Instead, we would like to suggest that cancer registries provide the ideal opportunity for a solution. The Scandinavian countries, as well as many American states, have population-based cancer registries in place and also either maintain birth registries or collect maternal smoking behavior on birth certificates. These countries are also those that would most benefit from breakthroughs in testicular cancer research as they have the highest testicular cancer rates in the world. Ideally, some large cohorts or countries with cancer registries may already have data on maternal alcohol consumption and should be urged to use this resource to enhance the body of available evidence. Large cohorts with prospectively collected maternal drinking could link to cancer registries, potentially making older data available now for a new purpose. Alternatively, governments have but to add collection of maternal drinking behaviors to their birth certificates and eventually it would be possible to evaluate the association with testicular cancer. This solution would build upon existing cancer registry and birth certificate infrastructures in order to produce high quality data from population-based cohorts, thereby reducing bias and avoiding small sample sizes. Opportunities for investigating the effects of other prenatal exposures on testicular cancer would also be presented by this approach. For testicular cancer – a rare cancer thought to originate from prenatal exposure but diagnosed decades later – linking cancer data to prospectively collected data on maternal pregnancy behavior may be the only way to determine the true causes of increasing incidence.

Written Morgana L. Mongraw-Chaffin, MPH and Barbara A. Cohn, MD
as part of Beyond the Abstract on UroToday.com

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