Diabetes and Pancreatic Cancer: Both Cause and Effect
Menée aux Etats-Unis à partir des données d'une cohorte multi-ethnique incluant 48 995 participants afro-américains et latinos, cette étude évalue l'association entre un diabète et le risque de cancer du pancréas (15 833 cas de diabète; 408 cas de cancer du pancréas)
By now, it is known that diabetes mellitus is a risk factor for pancreatic cancer. The special section on pancreatic cancer in the American Cancer Society’s Cancer Facts & Figures 2013 (1) states, “About 25% of patients with pancreatic cancer have diabetes mellitus at diagnosis, and roughly another 40% have pre-diabetes,” that “patients with long-term (five or more years) type II diabetes have a 50% increased risk of pancreatic cancer” and “pancreatic cancer can cause diabetes, and sometimes diabetes is an early sign of the tumor.” The direction of association goes both ways. Even though it takes about 10 to 15 years from pancreatic cancer initiation to diagnosis (2), most observable changes occur late in the disease course, though the trend in weight loss and cachexia is seen beginning perhaps 18 to 21 months before diagnosis (3), and we have shown that behaviors such as quitting cigarette smoking and starting proton pump inhibitor heartburn medication use and episodes of pancreatitis can be observed up to about two to three years before diagnosis as well (4). To date, most studies of the bi-directional temporal association between diabetes and pancreatic cancer have largely examined white and Asian populations. In this issue of the Journal, Setiawan and colleagues have extended this association to African and Hispanic Americans (5). In spite of the 60% higher lifetime risk of diabetes in these groups compared with white Americans (6), Setiawan and colleagues have shown that the same bi-directional association between diabetes and pancreatic cancer applies to them, with risk magnitudes comparable to those in other studies. It is a challenge to separate a causal involvement of diabetes mellitus (T2DM) in the origin of pancreatic cancer from diabetes as a result of pancreatic disease (T3cDM), in part because the risk relationship in the time before diagnosis is a continuum. Figure 1 shows the temporal pattern of risk according to years before diagnosis. In this figure, risk associations given in 13 reports (4,5,7–16) representing 37 to 41 individual studies (depending upon time point) are plotted, along with a random-effects meta-analysis value for each of the time intervals. Within two to three years of diagnosis, the average risk association is greater than twofold, whereas by five years before diagnosis, it settles down to near the 50% elevation noted by the American Cancer Society.