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Genetic Susceptibility and High Risk Groups for Pancreatic Cancer

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Pancreatic Cancer

Abstract:

Cancer develops because of a series of unfortunate events. The order of events defines a progression from normal cells through premalignant lesions to malignancy. A limited number of possible forms of progression are possible and initiation of this progression does not mean that a cancer will develop. The improbable events will have to happen in particular types of cells, quite probably at specific points in development. Cancer is a common disease only because the product of a large number of small probabilities is multiplied by the very large number of susceptible cells. The probability and consequences of mutation, epigenetic changes, infection, and other nonmalignant diseases are all determined by interaction between genotype and environment. On this basis many genes are involved in determining cancer risk; most of these have common allelic variants; subtle differences in the efficiency of these genes will impact on the probability of tumorigenic events. In combination, these will make large differences not just to the chance of developing cancer but also to the pathway that will lead to that cancer and the prognosis for the patient. This multigene effect is by far the most important element of genetic susceptibility, but it is unlikely to result in a significant family history of cancer. As pancreatic cancer is relatively uncommon, a family history spanning multiple generations is indicative of a rare (mutant) variant in a single gene. In reality, the consequence of inheriting such a high-risk allele will be dependent on a broader genetic context, and therefore, there is no such thing as a truly monogenic predisposition; but in certain families cancer does segregate with specific mutant alleles. In this chapter the way in which germline variation influences different stages of pancreatic cancer progression is discussed in order to explain why certain individuals should be considered as high risk. This has consequences for the management of a patient after cancer diagnosis but also for surveillance and screening, which will be covered in more detail in a separate chapter.

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Greenhalf, W., Neoptolemos, J. (2010). Genetic Susceptibility and High Risk Groups for Pancreatic Cancer. In: Pancreatic Cancer. Springer, New York, NY. https://doi.org/10.1007/978-0-387-77498-5_24

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