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