INK4/ARF germline alterations in pancreatic cancer patients.
BACKGROUND
Roughly 40% of germinal mutations in melanoma families (MF) affect p16(INK4a) and p14(ARF). We investigated the association between INK4/ARF alterations and the occurrence of pancreatic cancer in MF and in sporadic pancreatic cancer (SPC) patients.


METHODS
Forty-nine MF, 66 SPC cases and 54 controls were enrolled. The INK4/ARF locus was screened.


RESULTS
As compared with the general population, the risk of pancreatic cancer (PC) was increased 9.4-fold [95% confidence interval (CI) 2.7-33.4] and 2.2-fold (95% CI 0.8-5.7) in G101W-positive and -negative MF, respectively, while mean ages at onset were 61 and 77 years, respectively. A 1.7 (95% CI 1.06-2.79) increased risk of cancer at any site was observed among first-degree relatives of SPC cases as compared with controls. The G101W founder mutation was detected in 4% of SPC cases but the rate increased to 13% when tumor clustering in either branch of families was taken into account. One G101W-positive PC patient with a melanoma in a first-degree relative harbored a germline deletion of the second allele, including exon 1B.


CONCLUSIONS
The presence of a deletion including exon 1B in two PC patients points to the involvement of p14(ARF) in the development of PC and may suggest that the increased risk of PC in MF is caused by impairment of both loci.
Ghiorzo
P
P
Dipartimento di Oncologia, Biologia e Genetica (DOBiG), Università degli Studi di Genova, Genova, Italy.
Pastorino
L
L
Bonelli
L
L
Cusano
R
R
Nicora
A
A
Zupo
S
S
Queirolo
P
P
Sertoli
M
M
Pugliese
V
V
Bianchi-Scarrà
G
G
D000230:Adenocarcinoma / Q000453:epidemiology / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004252:DNA Mutational Analysis; D005260:Female; D019942:Genes, p16; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D015994:Incidence; D008297:Male; D008545:Melanoma / Q000453:epidemiology / Q000235:genetics / Q000503:physiopathology; D008875:Middle Aged; D008969:Molecular Sequence Data; D010190:Pancreatic Neoplasms / Q000453:epidemiology / Q000235:genetics*; D010375:Pedigree; D016133:Polymerase Chain Reaction; D025803:Tumor Suppressor Protein p14ARF / Q000235:genetics*
D025803:Tumor Suppressor Protein p14ARF