Incidence and mortality from non-Hodgkin lymphoma in Europe: The end of an epidemic? Cristina Bosetti 1 * , Fabio Levi 2 , Jacques Ferlay 3 , Franca Lucchini 2 , Eva Negri 1 and Carlo La Vecchia 1,4 1 Istituto di Ricerche Farmacologiche ‘‘Mario Negri’’, Via Giuseppe La Masa, 19, 20156 Milan, Italy 2 Unit  e d’ epid emiologie du Cancer et Registres Vaudois et Neuchaˆtelois des Tumeurs, Institut de M edecine Sociale et Pr eventive (IUMSP), Centre Hospitalier Universitaire Vaudois et Universit  e de Lausanne, Bugnon 17, 1005 Lausanne, Switzerland 3 International Agency for Research on Cancer, Lyon, France 4 Istituto di Statistica Medica e Biometria ‘‘G.A. Maccacaro’’, Universit ` a degli Studi di Milano, Via Venezian 1, 20133 Milan, Italy Non-Hodgkin lymphomas (NHL) are among the few neoplasms whose incidence and mortality have been rising in Europe and North America over the last few decades. To update trends from NHL, we considered mortality data up to 2004 in several Euro- pean countries, and for comparative purpose in the USA and Japan. We also analyzed patterns in incidence for selected Euro- pean countries providing national data. In most European coun- tries, NHL mortality rose up to the mid 1990s, and started to level off or decline in the following decade. The rates were, however, still increasing in eastern Europe. Overall, in the European Union, mortality from NHL declined from 4.3/100,000 to 4.1 in men and from 2.7 to 2.5 in women between the late 1990s and the early 2000s. Similarly, NHL mortality rates declined from 6.5/100,000 to 5.5 in US men and from 4.2 to 3.5 in US women. In most coun- tries considered, NHL incidence rates rose up to 1995–99, while they tended to level off or decline thereafter, with particular favorable patterns in countries from northern Europe. Thus, the epidemic of NHL observed during the second half of the 20th cen- tury has now started to level off in Europe as in other developed areas of the world. ' 2008 Wiley-Liss, Inc. Key words: Europe; incidence; mortality; non-Hodgkin lymphoma; trends Non-Hodgkin lymphomas (NHL) are among the few neoplasms whose incidence and mortality rates had been rising for both sexes in Europe and North America since the 1970s. 1–4 Over the last 2 decades, NHL mortality rates in the European Union (EU) rose to 4.4/100,000 men and to 2.8/100,000 women (age-standardized, world population). Upward trends were observed also in the USA, whose rates approached 6/100,000 men and 4/100,000 women in the late 1990s, and, although to a smaller extent, in Japan (3.7/ 100,000 men and 1.9/100,000 women). 2 To update trends from NHL, we have considered mortality data up to 2004 in several European countries, and for comparative purpose in the USA and Japan. We have also contrasted trends in incidence with those in mortality for 11 European countries pro- viding national incidence data. Material and methods Official death certification data from NHL for 29 European countries, plus the USA and Japan, for the period 1980–2004 were derived from the WHO database available on electronic support. 5 Data for Croatia, the Czech Republic and Slovenia were available only since 1985; for Estonia, Lithuania and Slovakia since 1990; for Latvia, Poland, Romania and the Russian Federation since 1995. For Belgium data were available only up to 1997; for Den- mark up to 2001; for Italy up to 2002; and for Portugal up to 2003. The European Union (EU 27) was defined as the 27 member states as since January 2007 (i.e., Austria, Bulgaria, the Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Lithuania, Luxembourg, Malta, The Neth- erlands, Portugal, Slovakia, Slovenia, Spain, Sweden, UK), with the exclusion of Cyprus (no data available), Belgium, Latvia Poland and Romania (which provided data only for a limited num- ber of years in the period considered). In the 2 decades considered, 3 different Revisions of the Inter- national classification of diseases (ICD) were used. 6–8 NHL were coded as 200, 202, 208, 209 in the 8th ICD Revision, as 200, 202 in the 9th ICD Revision and as C82-85 and C96 in the 10th ICD Revision. There were, however, no major differences in classifica- tion and grouping of NHL across the 3 ICD Revisions. Estimates of the resident population, based on official censuses, were obtained from the same WHO database. 5 From the matrices of certified deaths and resident population, age-specific rates for each 5-year age group and calendar period were computed. Age- standardized rates per 100,000, at all ages and truncated at age 35–64 years, were computed using the direct method, based on the world standard population. 9 In a few countries, data were missing for part of 1 or more calendar years. No extrapolation was made for missing data. Incidence data for 11 European countries providing national data at least since the early 1990s onwards were extracted from the successive volumes of Cancer Incidence in Five Continents. 10 Additional more recent information was found in various national cancer registry reports available in Internet. 11–17 Results Table I shows the age-standardized mortality rates from NHL per 100,000 men and women in selected European countries, the USA and Japan, in 1990–94, 1995–99 and 2000–04, and the corresponding change in rates. NHL mortality rose up to the mid 1990s in most Euro- pean countries, while it started to decline in many European countries over the last decade considered. The rates were, however, still increas- ing in countries from eastern Europe, such as Croatia, Estonia, Lithua- nia, Romania, the Russian Federation, Slovakia and Slovenia. Changes for most smaller countries were not statistically significant and should be interpreted cautiously, since they can be at least partly explained by random variation. Overall, in the EU, mortality from NHL declined from 4.3/100,000 to 4.1 in men and from 2.7 to 2.5 in women between the late 1990s and the early 2000s. Similarly, NHL mortality rates declined from 6.5/100,000 to 5.5 in US men and from 4.2 to 3.5 in US women, respectively. Corresponding values were 3.9 and 3.7 in Japa- nese men, and 1.98 and 1.99 in Japanese women. The patterns of NHL mortality in middle-aged populations (35– 64 years) were similar—and, if anything, more favorable—to those for all ages in most European countries, as in USA and Japan (Table II). Figure 1 gives the trends in overall mortality from NHL in the EU, in the USA and Japan. Mortality rates steadily increased in Grant sponsors: Italian and Swiss Leagues Against Cancer, Swiss Foun- dation for Research Against Cancer, Italian Association for Cancer Research. *Correspondence to: Istituto di Ricerche Farmacologiche ‘‘Mario Negri’’, Via Giuseppe La Masa 19, 20156 Milan, Italy. Fax: 139-0233200231. E-mail: bosetti@marionegri.it Received 6 March 2008; Accepted after revision 6 May 2008 DOI 10.1002/ijc.23722 Published online 7 August 2008 in Wiley InterScience (www.interscience. wiley.com). Int. J. Cancer: 123, 1917–1923 (2008) ' 2008 Wiley-Liss, Inc. Publication of the International Union Against Cancer