20 January 2019
Pancreatic cancer is one of the world’s deadliest cancers, often diagnosed at a late stage due to its lack of early symptoms. The difficulty in treating the disease in its later stages means eﬀective prevention is necessary.
Progress has been made in identifying the risk factors that cause pancreatic cancer. Mattias Johansson is a physicist-turned-geneticist working for the International Agency for Research on Cancer in Lyon, France. With his colleagues, Johansson has been able to home in on speciﬁc causal risk factors by looking at how genetic ‘markers’ correlate with pancreatic cancer.
“The classic example is coﬀee drinkers having a higher risk of lung cancer. In reality, that’s because coﬀee drinkers tend to smoke more than non-drinkers and, of course, it’s the smoking that is the real risk factor for the cancer. We call this phenomenon ‘confounding’,” explains Johansson.
Johansson and his team identified the DNA sequences associated with suspected risk factors for pancreatic cancer, such as obesity, body shape, insulin resistance, and type II diabetes. They then analysed the genetics of more than 14,000 individuals to see how the ‘markers’ correlated with pancreatic cancer.
Obesity and high insulin levels were shown to be causal factors for pancreatic cancer, while type II diabetes was among the confounded, non-causal traits. “For obesity, it was really conﬁrmatory—this is a risk factor that everyone thought was causal, so it was reassuring to see that hold up in this analysis,” Johansson says. He explains that the complexity of diabetes progression means caution must be exercised when interpreting its apparent lack of association.
Obesity and insulin, however, are a little more clear-cut. “There are a number of hypotheses as to how obesity leads to cancer. These include hormonal imbalances, inﬂammation, and the elevation of insulin levels. Insulin itself has various tumour-stimulating effects, and this at least partially explains why obese people have a higher risk of pancreatic cancer.”
Johansson has worked in the ﬁeld for almost 15 years, but says it’s just now that these lines of inquiry are really starting to pay oﬀ, thanks to the public genetic databases that allow for large-scale investigations into how our DNA translates into our health in life. The benefits cannot be overstated: “It directly informs our understanding of what causes a disease, which is essential in order to prevent it.”
- | Carreras-Torres, R., Johansson, M., Gaborieau, V., Hay cock, P. C., Wade, K. H. et al. Journal of the National Cancer Institute 109 (2017).8 | article