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  • Review Article
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Identifying people at a high risk of developing pancreatic cancer

Nature Reviews Cancer volume 13, pages 66–74 (2013)Cite this article

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Key Points

  • Familial cancer registries have had a key role in our understanding of the aetiology of many cancer types, such as breast and colon cancer.

  • As pancreatic cancer is a leading cause of cancer death and because it has the poorest prognosis of any major tumour type, familial pancreatic cancer registries are an important tool for investigating the genetic aetiology of this devastating disease.

  • By studying the families that are enrolled in our familial pancreatic cancer registry we have been able to identify several familial pancreatic cancer susceptibility genes, conduct some of the first early detection screening trials for pancreatic cancer and have begun to understand the potential of personalized treatment for this disease.

  • Registries also allow for the prospective follow-up of a population at a high risk of pancreatic cancer, a disease that is traditionally difficult to study owing to its rarity.

  • The adaptive nature of family registries has allowed for the rapid adoption of new technologies, such as genome sequencing for gene discovery.

Abstract

Pancreatic cancer is a leading cause of cancer death, and it has the poorest prognosis of any major tumour type. Familial pancreatic cancer registries are important for investigating the genetic aetiology of this devastating disease. Using data from our familial pancreatic cancer registry and other registries, this Review discusses the usefulness of family registries in the study of pancreatic and other cancers, and also how such registries provide a unique opportunity for laboratory, population and clinical research.

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Figure 1: Overview of the research conducted with pancreatic cancer family registry data.

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Acknowledgements

A special thank you to all of the patients and families who participate in the National Familial Pancreas Tumor Registry and other pancreatic cancer family studies without whom this research would not be possible. The author would also like to thank R. Hruban, K. Brune, E. Palmisano and D. Echavarria. A.P.K. receives support from the NCI SPORE in Gastrointestinal Cancer CA62924, RO1 CA154823 and the Sol Goldman Pancreatic Cancer Research Center.

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Authors and Affiliations

  1. Departments of Oncology and Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins School of Medicine, Baltimore, 21231, Maryland, USA

    Alison P. Klein

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Competing interests

A.P.K. is a co-inventor of PALB2 patent, licensed through Johns Hopkins to Myriad Genetics.

Related links

Glossary

Prospective

A term used in epidemiological studies, when a population is defined and then followed in time so that the occurrence of particular events or outcomes can be observed.

Case–control studies

Retrospective observational epidemiological studies of individuals with a given condition (case) who are identified along with a comparison group of individuals without the disease (controls). The frequency or, more specifically, the odds of exposure are then compared between these two groups.

Penetrance

The probability of developing a given phenotype that is conditional on a given genotype. For example, the probability of developing breast cancer given that one carries a mutation in BRCA1.

Retrospective studies

Identification of a group of individuals from historical data and reconstruction of their exposure history and occurrence of disease until the present time. Disease outcome between exposed and unexposed individuals is compared.

Lynch syndrome

Also known as hereditary non-polyposis colorectal cancer. An autosomally dominant inherited cancer syndrome that is most notably known for a high risk of colon cancer in both genders and of endometrial cancer in women.

Ascertainment (selection) bias

When families are selected based on a particular phenotype (that is, multiple cases of cancer), any analyses using these families that do not properly control for this selection can lead to biased results.

Peutz–Jeghers syndrome

An autosomally dominant inherited syndrome that is characterized by hamartomatous polyps of the gastrointestinal tract and pigmented macules on the buccal mucosa.

Allelic heterogeneity

Mutations located in different alleles in the same gene that can cause a given genetic disease of phenotype.

Locus heterogeneity

When the same genetic disease or phenotype occurs but can be due to a single genetic mutation in more than one gene.

Ataxia telangiectasia

An autosomal recessive condition caused mutations in the ATM gene. This syndrome is characterized by immunodeficiency, decreased DNA damage repair and neurological abnormalities.

Phenocopies

Non-genetic or sporadical occurrences of a phenotype when the same phenotype has been shown to occur owing to a genetic mutation in other individuals.

Area under the receiver operator characteristic (ROC) curve

(AUC). A graphical plot created by plotting the fraction of true positives out of the positives versus the fraction of false positives out of the negatives, at various threshold settings. The true positive rate is also known as sensitivity, and the false-positive rate is one minus the specificity or true negative rate. The area under the curve represents the probability that an individual with the disease has a higher score than an individual without the disease.

Cross-sectional

A type of epidemiological study in which outcomes and exposures are assessed at a single point in time.

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Klein, A. Identifying people at a high risk of developing pancreatic cancer. Nat Rev Cancer 13, 66–74 (2013). https://doi.org/10.1038/nrc3420

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