world cancer report - iarc

Fig. 5.124 Pancreatic duct showing high-grade
intraepithelial neoplasia.
Fig. 5.125 Well-differentiated, mucus-secreting
invasive ductal adenocarcinoma of the pancreas.
Hereditary conditions
Around 10% of cases of pancreatic cancer
exhibit some degree of familial risk, this
fraction being the highest for any human
organ site [6]. In this context, germline
mutations have been identified in a number
of oncogenes and tumour suppressors,
including BRCA2, (predisposing to
breast and pancreatic carcinoma) and
p16 INK4 (predisposing to melanoma and
pancreatic cancer) (Table 5.13). The
STK11/LKB1 gene is mutated in Peutz-
Jeghers syndrome patients, this group
being predisposed to pancreatic cancer
[7]. Sufferers from hereditary pancreatitis
experience attacks of acute pancreatitis
from an early age and face a 40% risk of
cancer by age 70. Most families appear to
possess one of two mutations in the
cationic trypsinogen gene (chromosome
7q35) [8] which cause the production of a
mutant protein. Consequently, associated
enzymatic activity is not inactivated and is
hypothesized to contribute to autodigestion
of the pancreas and pancreatitis; cancer
may then be a consequence of the
prolonged inflammatory microenvironment
in the pancreas. Other conditions
250 Human cancers by organ site
Gene Chromosome Mechanism of alteration % of cancers
Oncogenes
KRAS 12p Point mutation > 90
MYB, AKT2, AIB1 6q, 19q, 20q Amplification 1 10-20
ERBB2 (HER/2-neu) 17q Overexpression 70
Tumour suppressor genes
p16 INK4A 9p Homozygous deletion 40
Loss of heterozygosity 40
and intragenic mutation
Promoter hypermethylation 15
p53 17p Loss of heterozygosity 50-70
and intragenic mutation
DPC4 18q Homozygous deletion 35
Loss of heterozygosity 20
and intragenic mutation
BRCA2 13q Inherited intragenic 7
mutation and loss
of heterozygosity
MKK4 17p Homozygous deletion, 4
loss of heterozygosity
and intragenic mutation
LKB1/STK11 19p Loss of heterozygosity 5
and intragenic mutation,
homozygous deletion
ALK5 and TGF βR2 9q, 3p Homozygous deletion 4
DNA mismatch repair
MSH2, MLH1, others 2p, 3p, others Unknown