INTRODUCTION: As large scale genetic analysis becomes increasingly efficient, attention is turning to problems arising from inaccurate measurement of the phenotype. We have investigated the underlying basis of variation in disease severity in the large intestine of @entity1412 ( @entity1412 ) @entity1 . The development of objective and reproducible measures may have future use in genetic studies, such as analysis of modifier genes. METHODS: We examined the ratio of @entity652 to crypts from microscopic slides taken from all parts of the colon of 44 resected @entity1412 specimens. These findings were compared with a carefully reported macroscopic polyp count. Age dependency of @entity652 counts (in the period around colectomy) was also analysed. RESULTS: The @entity652 :crypt ratio strongly correlated with reported macroscopic polyp count (r=0.82, p<0.001) with no significant residual variation. Polyp density measured using the @entity652 : crypt ratio did not vary significantly within an individual colon. Apparent visible variation in polyp density within any colon was not found at the microscopic level. There was no detectable age related increase in macroscopic @entity652 count between siblings over the age range at which colectomies were performed. DISCUSSION: The severity of @entity1412 in @entity1412 can be determined accurately by counting the @entity652 :crypt ratio in sections derived from stored tissue blocks. Variation between @entity1 -dependent on @entity1412 genotype and, probably, modifier genes-is manifest at both the microscopic and macroscopic levels. Thus variation in disease severity is more likely to result from different rates of @entity5 initiation than from differences in progression of @entity5 . The absence of a detectable relationship between @entity652 number and age (over the range studied) suggests that most @entity5 may be initiated relatively early in the @entity1 's life, perhaps at a time of particular susceptibility.

Variability in the severity of colonic disease in @entity1412 results from differences in XXXX initiation rather than progression and depends relatively little on @entity1 age.

@entity1 :: ('9606', 'Species') :: ['patients', 'patient'] @entity652 :: ('MESH:D000236', 'Disease') :: ['adenomas', 'adenoma'] @entity1412 :: ('MESH:D011125', 'Disease') :: ['familial adenomatous polyposis', 'APC', 'colonic polyposis', 'FAP'] @entity5 :: ('MESH:D009369', 'Disease') :: ['microadenomas to macroscopic tumours', 'tumours', 'tumour']
@entity5 :: (MESH:D009369,Disease) :: ['tumour']
