Clinical and genetic characteristics of hereditary pancreatitis in Europe.
OBJECTIVE
Hereditary pancreatitis is an autosomal dominant disease that is mostly caused by cationic trypsinogen (PRSS1) gene mutations. The aim was to determine phenotype-genotype correlations of families in Europe.


METHODS
Analysis of data obtained by the European Registry of Hereditary Pancreatitis and Pancreatic Cancer was undertaken using multilevel proportional hazards modelling.


RESULTS
There were 112 families in 14 countries (418 affected individuals): 58 (52%) families carried the R122H, 24 (21%) the N29I, and 5 (4%) the A16V mutation, 2 had rare mutations, and 21 (19%) had no PRSS1 mutation. The median (95% confidence interval [CI]) time to first symptoms for R122H was 10 (8, 12) years of age, 14 (11, 18) years for N29I, and 14.5 (10, 21) years for mutation negative patients (P = 0.032). The cumulative risk (95% CI) at 50 years of age for exocrine failure was 37.2% (28.5%, 45.8%), 47.6% (37.1%, 58.1%) for endocrine failure, and 17.5% (12.2%, 22.7%) for pancreatic resection for pain. Time to resection was significantly reduced for females (P < 0.001) and those with the N29I mutation (P = 0.014). The cumulative risk (95% CI) of pancreatic cancer was 44.0% (8.0%, 80.0%) at 70 years from symptom onset with a standardized incidence ratio of 67% (50%, 82%).


CONCLUSIONS
Symptoms in hereditary pancreatitis start in younger patients and endpoints take longer to be reached compared with other forms of chronic pancreatitis but the cumulative levels of exocrine and endocrine failure are much higher. There is an increasingly high risk of pancreatic cancer after the age of 50 years unrelated to the genotype.
Howes
Nathan
N
Department of Surgery, University of Liverpool, United Kingdom.
Lerch
Markus M
MM
Greenhalf
William
W
Stocken
Deborah D
DD
Ellis
Ian
I
Simon
Peter
P
Truninger
Kaspar
K
Ammann
Rudi
R
Cavallini
Giorgio
G
Charnley
Richard M
RM
Uomo
Generoso
G
Delhaye
Miriam
M
Spicak
Julius
J
Drumm
Brendan
B
Jansen
Jan
J
Mountford
Roger
R
Whitcomb
David C
DC
Neoptolemos
John P
JP
D000328:Adult; D017677:Age Distribution; D017668:Age of Onset; D016001:Confidence Intervals; D005060:Europe / Q000453:epidemiology; D005260:Female; D030342:Genetic Diseases, Inborn / Q000175:diagnosis / Q000453:epidemiology; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D006579:Heterozygote; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010195:Pancreatitis / Q000453:epidemiology* / Q000235:genetics* / Q000601:surgery; D010375:Pedigree; D017354:Point Mutation; D011336:Probability; D011379:Prognosis; D012042:Registries; D015203:Reproducibility of Results; D018570:Risk Assessment; D012720:Severity of Illness Index; D017678:Sex Distribution; D015996:Survival Rate; D014357:Trypsin; D014362:Trypsinogen / Q000235:genetics*
D014362:Trypsinogen; C489303:PRSS1 protein, human; D014357:Trypsin