4th Edition

Chapter 8: The belly of an emperor

In 1821, Napoleon Bonaparte, the former Emperor of France, died in exile at Longwood House, St Helena. His health had been declining over a number of months with abdominal pain, weakness and vomiting, which he attributed to mistreatment by his English captors. An autopsy performed following his death concluded that the cause of death was stomach cancer, and indeed, there was a strong history of stomach cancer in his family, although longstanding Helicobacter pylori infection may have contributed.

The most common germline mutations associated with familial gastric cancer are mutations of E-cadherin (CDH1) gene, a tumour suppressor gene.

  • 1. What features in the clinical history make an inherited genetic cancer predisposition more likely?

    Correct answer:

    • Family history of cancer in multiple relatives
    • Cancer occurring at a younger age (e.g. colon cancer in teens in familial adenomatous polyposis (FAP))
    • Multiple primary cancers occurring (e.g. bilateral retinoblastomas)
    • Multiple types of cancers (e.g. medullary thyroid cancer and phaeochromocytoma in MEN2)

  • 2. What is the relationship between the site of the oesophageal cancer, its histological subtype and risk factors?

    Correct answer:

    • BRCA2
    • Cowden’s syndrome
    • Familial polyposis coli including Gardner syndrome (FAP with dental cysts and desmoids tumours) and Turcot’s syndrome (FAP with CNS tumours)
    • Hereditary non-polyposis colon cancer (Lynch type II)
    • Juvenile polyposis syndrome
    • Li--Fraumeni syndrome
    • MutYH associated polyposis
    • Peutz-Jeghers syndrome

Syndrome Malignancies Inheritance Gene Function
Hereditary breast and ovarian cancer 2 (BRCA2) Breast, ovarian, prostate, pancreas AD BRCA2 Genome integrity
Cowden Breast, thyroid, gastrointestinal, pancreas AD PTEN Signal transduction (tyrosine phosphatase)
Familial polyposis coli Colon, upper gastrointestinal AD APC Cell adhesion
Hereditary non-polyposis colon cancer (Lynch type II) Colon, endometrium, ovarian, pancreatic, gastric AD MSH2,MLH1,PMS1,PMS2 DNA mismatch repair
Juvenile polyposis syndrome GI hamartomas (colon, stomach, ileum, rectum), colon cancer AD SMA, D4, BMP, R1A Cell signalling
Li-Fraumeni syndrome Sarcoma, breast, osteosarcoma, leukaemia, glioma, adrenocortical AD p53 Genome integrity
MutYH associated polyposis Colorectal cancer AR MYH DNA mismatch repair
Peutz-Jeghers syndrome GI polyposis/cancer, mucosal pigmentation, sex cord tumoursl AD STK11 Cell polarity

Nineteen years later, Napoleon’s grave was opened and his body was returned to Paris to be finally interred in the magnificent tomb at the church of the Invalides, where it rests today. A popular alternative hypothesis proposed that his death was a consequence of chronic arsenic poisoning by his English captors.

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