From the yahoogroups FA mailing list

Date: Thu, 19 Jun 2003 16:05:44 -0400
From: "Alter, Blanche (NIH/NCI)" <alterb@mail.nih.gov>
Subject: Pancreatic cancer

I want to respond to the Falistserv request that a medical person comment on
the recent report from Dr Kern's lab at Hopkins, in which they found a small
number of FA mutations in patients with pancreatic cancer: In one FANCC
case, the mutation was only in the tumor, suggesting that the FA gene had
been mutated during tumor development, in a person who did not carry a
germline FA mutation. In the other FANCC case, the FA mutation is said to be
"mild". It is apparently not clear whether that is a disease-associated
mutation, or just a polymorphism (a change which has no disease-related
reelvance). In the FANCG case, there was no germline material available, so
while it is listed as "probably inherited", this cannot be proven.

There are two issues:
1. Do FA carriers have an increased risk of pancreatic cancer? We do
not have sufficient data yet, although our protocol and the IFAR study are
obviously looking at this. So far, nothing stands out in our own data set,
and so the FA relatives should NOT be overly concerned. The lifetime risk of
pancreatic cancer is 1/30 of 1% (ie 0.03%). Even if FA carrier status
increased that by 10-fold, it would still affect very few FA carriers
overall. And, we do not know whether the FA gene does increase the risk.
In addition, Dr Kern reported to me that he has found a few FA gene
variants in tumors that have never been reported in FA patients, and thus he
knows nothing about their relationship to FA.
2. What is the role of FA genes in pancreatic carcinogenesis? In the
general population, some pancreatic cancers may have mutations in FA genes.
This may make them more sensitive to the kinds of chemotherapy that induce
DNA breaks. This means that the subset of patients with pancreatic ca in
whom the FA or the BRCA2 pathway are disrupted may benefit from treatment
with that type of chemotherapy, since their tumor cells may be overly
sensitive.

Both of these are research questions. We are collaborating with Dr Kern on
this subject. When we have new data of significance, we will share it with
the scientific community, and of course with the FA families.

I hope this answers all the questions that you have raised?

Blanche P Alter, MD, MPH (6/19/03)
Clinical Genetics Branch
Division of Cancer Epidemiology and Genetics
National Cancer Institute