Age-period-cohort modelling of non-Hodgkin's lymphoma incidence in a French region: a period effect compatible with an environmental exposure

BACKGROUND The incidence of non-Hodgkin's lymphoma (NHL) has risen steadily during the last few decades in all geographic regions covered by cancer registration for reasons that remain unknown. The aims of this study were to assess the relative contributions of age, period and cohort effects to NHL incidence patterns and therefore to provide clues to explain the increasing incidence. METHODS Population and NHL incidence data were provided for the Doubs region (France) during the 1980-2005 period. NHL counts and person-years were tabulated into one-year classes by age (from 20 to 89) and calendar time period. Age-period-cohort models with parametric smooth functions (natural splines) were fitted to the data by assuming a Poisson distribution for the observed number of NHL cases. RESULTS The age-standardised incidence rate increased from 4.7 in 1980 to 11.9 per 100,000 person-years at risk in 1992 (corresponding to a 2.5-fold increase) and stabilised afterwards (11.1 per 100,000 in 2005). Age effects showed a steadily increasing slope up to the age of 80 and levelled off for older ages. Large period curvature effects, both adjusted for cohort effects and non-adjusted (p < 10-4 and p < 10-5, respectively), showed departure from linear periodic trends; period effects jumped markedly in 1983 and stabilised in 1992 after a 2.4-fold increase (compared to the 1980 period). In both the age-period-cohort model and the age-cohort model, cohort curvature effects were not statistically significant (p = 0.46 and p = 0.08, respectively). CONCLUSIONS The increased NHL incidence in the Doubs region is mostly dependent on factors associated with age and calendar periods instead of cohorts. We found evidence for a levelling off in both incidence rates and period effects beginning in 1992. It is unlikely that the changes in classification (which occurred after 1995) and the improvements of diagnostic accuracy could largely account for the 1983-1992 period-effect increase, giving way to an increased exposure to widely distributed risk factors including persistent organic pollutants and pesticides. Continued NHL incidence and careful analysis of period effects are of utmost importance to elucidate the enigmatic epidemiology of NHL.