Our Stolen Futurea book by Theo Colborn, Dianne Dumanoski, and John Peterson Myers


  Porta, M, N Malats, M Jariod, JO Grimalt, J Rifa, A Carrato, L Guarner, A Salas, M Santiago-Silva, JM Corominas, M Andreu, FX Real. 1999. Serum concentrations of organochlorine compounds and K-ras mutations in exocrine pancreatic cancer. The Lancet 354:2125-2129

Porta 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.

Serum 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 (PCB 180).

Serum 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).

Tumors 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.

The 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."





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