Common susceptibility genes for cancer: search for the end of the rainbow

doi:10.1136/bmj.332.7550.1150

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Stuart G Baker, biostatistician (sb16i@nih.gov)1,
Jaakko Kaprio, genetic epidemiologist2

¹ National Cancer Institute, Bethesda MD 20892-7354, USA
² University of Helsinki, Helsinki, Finland

Correspondence to: S G Baker

Accepted 9 March 2006

The human genome map has started a hunt to find common genes that are associated with cancer. But new research questions the likelihood of success.

Huge resources are being invested in the search for common inherited genetic variants that increase susceptibility to cancer. However, these studies are expensive because they require large sample sizes to rule out false positive results (table).1 2 The US cancer genetic markers of susceptibility project (http://cgems.cancer.gov/), for example, will cost $14m (£7.9m; €11m). In addition, large replication studies may still be necessary to confirm generalisability to other populations. For these studies to eventually lead to a clinical therapeutic benefit, common genetic variants that increase susceptibility to cancer must exist and it must be feasible to rigorously evaluate the clinical benefit of targeting these common genetic variants. Both these requirements require formal consideration.

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Sample sizes required to make false positive results unlikely when testing association between genetic variant and cancer*

Common cancer susceptibility genes are unlikely

Devoting a large research effort to searching for common cancer susceptibility genes has several problems. The first is that recent research suggests these genes are unlikely to exist or, if they do, are unlikely to have much of an effect on the incidence of cancer. The early phases of carcinogenesis seem to entail alterations in the stroma (supporting tissue) rather than a genetic mutation of the parenchyma (functional tissue).3 4 Thus genetic susceptibility to cancer of the parenchyma (except for rare genes related to familial cancer) would have a relatively small role in the early stages of carcinogenesis. Moreover, a recent study could not find conclusive evidence of genetic alterations in the stroma,5 further diminishing the probable role of genetic susceptibility in early …