- There is far more cancer research than any other biomedical topic.
- Perhaps due primarily to the relative ease with which scientists can conduct genetic cancer research, nearly every human gene has associations with the disease in one way or another.
- A new paper questions the validity of many of these associations and suggests that researchers consider pursuing other avenues of investigation.
Cancer is, far and away, the most widely researched biological or biomedical topic, and for a good reason. In the United Kingdom, cancer will affect 1 out of every 2 people at some time in their lives.
However, a new analysis of the PubMed library of biomedical research literature finds that the search for connections between genes and cancer has created an overabundance of reported associations, making new research even more difficult.
At this point, almost all human genes have a connection with cancer in one way or another.
According to the article, which appears in Trends In Genetics, the PubMed library holds at least one paper on 17,371 human genes. Of these, 87.7% mention cancer in at least one publication.
Of the 4,186 genes that are the subjects of 100 or more PubMed articles, only three genes have no associations with cancer.
The author of the new paper, Dr. João Pedro de Magalhães of the University of Liverpool in the U.K., writes, “An incredible 24.4% of all publications associated with genes in PubMed mention cancer.”
Dr. de Magalhães suspects this wealth of associations has to do with how relatively easy it is to perform cancer research from a genetic perspective:
“Compared with other common diseases, such as heart or neurodegenerative diseases, cancer is also seemingly more straightforward to study, given the wide availability of materials, such as cell lines.
In other words, the experimental methods necessary to study cancer seem to have lower technical limitations compared with many other disease scenarios.”
Why the number of links is a problem
The many connections cited in research imply that nearly all genes are involved in cancer, which is improbable, asserts Dr. de Magalhães.
Associations are not necessarily evidence of actual causal relationships, so much of this research may amount to unhelpful statistical noise that makes productive analysis more difficult.
The analysis cites several ways in which the glut of reported associations inhibit worthwhile research:
- It undermines the integrity of grant awards since “The study of nearly any human gene can be justified (e.g., in grant applications) based on existing literature by its potential relevance to cancer,” says the study.
- Genome-wide studies and high-throughput analyses are more likely to capture an unhelpful range of gene/cancer associations, with so many existing in the literature. The paper finds a greater-than-99% chance of three or more genes finding their way into a result.
- Biases in cancer research publications can affect the integrity of network analyses, “such as protein-protein interactions, that are influenced by the number of studies of each protein.”
Dr. de Magalhães writes that researchers should be mindful of the bias toward seeking gene associations for cancer, considering it in their discussions with other researchers, and in appraising their work:
“In genetics and genomics, literally everything is associated with cancer. If a gene has not been associated with cancer yet, it probably means it has not been studied enough and will most likely be associated with cancer in the future.”
Says Dr. de Magalhães, “In a scientific world where everything and every gene can be associated with cancer, the challenge is determining which are the key drivers of cancer and more promising therapeutic targets.”
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