et al. compared 51 patients with pancreatic cancer with 26
hospital controls, and of the 51, analysed 34 cases with codon 12
K-ras mutations vs. 17 wild-type. The study raises questions
but allows no definitive conclusions.
concentrations of p,p'-DDT
and p,p'-DDE were significantly higher among the 51
cases of pancreatic cancer than among the 26 controls. Concentrations
among the cases with wild-type K-ras were similar to controls. Concentrations
of the three measured PCB congeners were higher in the 51 pancreatic
cancer cases, but differences were significant for only one congener
concentrations of p,p'-DDT and p,p'-DDE were significantly
higher in pancreatic cancer cases with a K-ras mutation than
in cases without a mutation. There was a strong association between
a specific codon substitution (glycine to valine at codon 12) and
both p,p'-DDT and p,p'-DDE concentrations (odds ratios
15.9, p=0.044 and odds ratio 24.1, p=0.28, respectively).
of patients in the mid and upper p,p'-DDT tertiles were more
than five times more likely and more than eight times more likely
to have a mutation, respectively, than tumors of cases in the lower
tertile. Similar trends were seen for p,p'-DDE.
authors observe that their results do not necessarily imply that
organochlorines play a direct part in activation of K-ras.
Rather, the compounds might enhance the effects of K-ras
mutagens or might provide a growth advantage to the mutated cells.
"The comparison of the 51 cases with the 26 controls suggests
that organochlorines might increase the risk of pancreatic cancer,
but the primary message of the comparison is that cases with mutated
K-ras had higher serum concentrations of organochlorines
than the general population (study base), whereas cases with wild-type
K-ras and controls had similar concentrations."