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Annals of Oncology 15:70-78, 2004
© 2004 European Society for Medical Oncology

Original Paper

INK4/ARF germline alterations in pancreatic cancer patients

Received 21 May 2003; revised 20 June 2003; accepted 12 August 2003

Background:

Roughly 40% of germinal mutations in melanoma families (MF) affect p16INK4a and p14ARF. We investigated the association between INK4/ARF alterations and the occurrence of pancreatic cancer in MF and in sporadic pancreatic cancer (SPC) patients.

Patients and 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 p14ARF in the development of PC and may suggest that the increased risk of PC in MF is caused by impairment of both loci.

P. Ghiorzo1, L. Pastorino1, L. Bonelli2, R. Cusano1, A. Nicora2, S. Zupo2, P. Queirolo2, M. Sertoli2, V. Pugliese2 and G. Bianchi-Scarrà1,*

1 Dipartimento di Oncologia, Biologia e Genetica (DOBiG), Università degli Studi di Genova, Genova; 2 Istituto Nazionale per la Ricerca sul Cancro (IST), Genova, Italy

Key words: CDKN2A, familial melanoma, G101W mutation, increased risk, p14ARF, pancreatic cancer


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