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Hereditary aspects of upper GI malignancy Eamonn Sheridan Consultant in Clinical Genetics
Familial tendancy to malignancy Tends to be dominant Early onset of disease Rare –FAP 1/8000 –HNPCC 1/2500 –Peutz Jeghers 1/50000 –Juvenile polyposis 1/100,000 –TOC two families Extra GIT features
Familial risks Expressed as odds ratios Oesophageal cancer 1.6 Gastric cancer Small bowel tumours No indication for screening at these levels of risk
Mendelian cancer predisposition syndromes FAP HNPCC Gastric cancer Peutz Jegher Juvenile polyposis
FAP Hundreds of colonic polyps in second and third decades Extracolonic manifestations Gastric polyps Duodenal polyps Clear excess of ampullary cancers
HNPCC No biological phenotype Amsterdam criteria RR stomach cancer 4.1 median age 54 RR small bowel 25 median age 53 RR Hepatobiliary system 4.9 age 66
Peutz Jegher syndrome Excess of small bowel tumours Difficult to identify Intusseception Obstruction Torsion
Dominant Gastric cancer extremely rare Few families only with multiple affecteds Mutations in -catenin gene Screening unproven
Oesophageal cancer Minimal familial tendancy Two large families with TOC Linked to chromosome 17 No gene as yet
Conclusions Low relative risk for most of these tumours May be significant risks if part of other syndrome Screening uncertain
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