Recent trends in colorectal cancer mortality in Europe

Authors

  • Cristina Bosetti,

    Corresponding author
    1. Dipartimento di Epidemiologia, Istituto di Ricerche Farmacologiche “Mario Negri,” Milan, Italy
    • Department of Epidemiology, Istituto di Ricerche Farmacologiche “Mario Negri,” Via Giuseppe La Masa 19 - 20156 Milan, Italy
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    • Tel.: +39-0239014.526, Fax: +39-0233200231

  • Fabio Levi,

    1. Unité d'épidémiologie du cancer et Registres vaudois et neuchâtelois des tumeurs, Institut de médecine sociale et préventive (IUMSP), Centre Hospitalier Universitaire Vaudois et Université de Lausanne, Lausanne, Switzerland
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  • Valentina Rosato,

    1. Dipartimento di Epidemiologia, Istituto di Ricerche Farmacologiche “Mario Negri,” Milan, Italy
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  • Paola Bertuccio,

    1. Dipartimento di Epidemiologia, Istituto di Ricerche Farmacologiche “Mario Negri,” Milan, Italy
    2. Dipartimento di Medicina del Lavoro, Sezione di Statistica Medica e Biometria “G.A. Maccacaro,” Università degli Studi di Milano, Milan, Italy
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  • Franca Lucchini,

    1. Unité d'épidémiologie du cancer et Registres vaudois et neuchâtelois des tumeurs, Institut de médecine sociale et préventive (IUMSP), Centre Hospitalier Universitaire Vaudois et Université de Lausanne, Lausanne, Switzerland
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  • Eva Negri,

    1. Dipartimento di Epidemiologia, Istituto di Ricerche Farmacologiche “Mario Negri,” Milan, Italy
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  • Carlo La Vecchia

    1. Dipartimento di Epidemiologia, Istituto di Ricerche Farmacologiche “Mario Negri,” Milan, Italy
    2. Dipartimento di Medicina del Lavoro, Sezione di Statistica Medica e Biometria “G.A. Maccacaro,” Università degli Studi di Milano, Milan, Italy
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Abstract

Colorectal cancer mortality has been declining over the last two decades in Europe, particularly in women, the trends being, however, different across countries and age groups. We updated to 2007 colorectal cancer mortality trends in Europe using data from the World Health Organization (WHO). Rates were analyzed for the overall population and separately in young, middle-age and elderly populations. In the European Union (EU), between 1997 and 2007 mortality from colorectal cancer declined by around 2% per year, from 19.7 to 17.4/100,000 men (world standardized rates) and from 12.5 to 10.5/100,000 women. Persisting favorable trends were observed in countries of western and northern Europe, while there were more recent declines in several countries of eastern Europe, including the Czech Republic, Hungary and Slovakia particularly in women (but not Romania and the Russian Federation). In 2007, a substantial excess in colorectal cancer mortality was still observed in Slovakia, Hungary, Croatia, the Czech Republic and Slovenia in men (rates over 25/100,000), and in Hungary, Norway, Denmark and Slovakia in women (rates over 14/100,000). Colorectal mortality trends were more favorable in the young (30–49 years) from most European countries, with a decline of ∼2% per year since the early 1990s in both men and women from the EU. The recent decreases in colorectal mortality rates in several European countries are likely due to improvements in (early) diagnosis and treatment, with a consequent higher survival from the disease. Interventions to further reduce colorectal cancer burden are, however, still warranted, particularly in eastern European countries.

In the European Union (EU), colorectal cancer mortality has been declining since the early 1980s by around 1% per year in women and since the early 1990s by 0.6% per year in men.1 Favorable trends in colorectal cancer mortality have also been observed in North America2, 3 and Japan.4, 5

Trends, however, differed across age groups, falls being generally larger in young and middle-age than in the elderly. Moreover, the declines in colorectal cancer mortality started earlier and were larger in most western and northern Europe, whereas trends were less favorable in Spain,6 other countries of southern Europe and, mostly, in central and eastern European countries. This has led to converging patterns of colorectal cancer mortality across various areas of Europe, though there were still some countries of central Europe, such as Hungary and the Czech Republic, with exceedingly high rates (i.e., around 35/100,000 men, comparable to lung cancer rates in a few major western European countries), and long-term upward trends.

To provide an updated picture of colorectal cancer mortality in Europe, we extended to 2007 analyses of trends in European countries and the EU as a whole, and used joinpoint regression analysis to identify significant changes in trends.7 We also focused on three separate age groups, i.e., young (30–49 years), middle-age (50–69 years) and elderly (≥70 years) population, to shed light on patterns of trends in various generations.

Material and Methods

We abstracted official death certification data for intestinal cancers (chiefly colon and rectum) for 34 European countries from the World Health Organization (WHO) database as available on electronic support for the period 1970–2007.8 For the Czech Republic, the Russian Federation, Slovakia and Slovenia, data were available since the early/mid 1980s; for Macedonia and Portugal data were available up to 2003; for Hungary, Slovakia and Spain up to 2005; for Bulgaria, Croatia, Denmark, Germany, Luxembourg, the Russian Federation and Ukraine up to 2006. The EU was defined as the 27 member states as in 2007, excluding Cyprus, whose data are unavailable, and Belgium, whose data are not available for most recent calendar years. In a few countries, data were missing for one or more calendar years; no extrapolation was made for missing years.

During the calendar period considered, three different revisions of the International Classification of Diseases (ICD) were used. Classification of cancer deaths was recoded, for all calendar periods and countries, according to the Tenth Revision of the ICD.9 To improve validity and comparability of data throughout different countries, we pooled together colon, rectum and “malignant neoplasms of other and ill-defined digestive organs” (ICD 10th: C17–C21, C26).

Estimates of the resident population, based on official censuses, were derived from the same WHO database.8 From the matrices of certified deaths and resident populations, we computed age-standardized rates at all ages and in three separate age groups (30–49, 50–69, ≥70 years), on the basis of the world standard population.10

We used the joinpoint regression analysis to identify the points where the trends in rates significantly changed.7 The estimated annual percent change (APC) was then computed for each of the identified trend by fitting a regression line to the natural logarithm of the rates using calendar year as the regressor variable (i.e., given y = a + bx, where y = ln(rate) and x = calendar year, the APC is estimated as 100*(eb − 1)). We also computed average annual percent changes (AAPC) over the last 5 and 10 years—based on the underlying joinpoint model—as a geometric weighted average of the APCs, with weights equal to the lengths of each segment over the specified fixed intervals.11 The computation of mortality rates and their standard errors was implemented in S-PLUS.12 The joinpoint regression analysis was performed using the “Joinpoint” software from the Surveillance Research Program of the U.S. National Cancer Institute.13

Results

Table 1 gives the overall age-adjusted mortality rates from colorectal cancer per 100,000 men and women in various European countries and in the EU around 1997 (1995–1999), 2002 (2000–2004) and in 2007, and the corresponding percent changes in rates. Around 1997, the highest mortality rates from colorectal cancer in men were in the Czech Republic, Hungary and Slovakia (over 30/100,000), followed by Croatia, Slovenia and Ireland (25 to 30/100,000). The lowest mortality rates were in Greece (10.4/100,000), Macedonia, Romania and Finland (around 12/100,000). In women, in 1997 the highest mortality rates from colorectal cancer were in Hungary, the Czech Republic, Denmark, Slovakia, Norway and Ireland (over 15/100,000), while the lowest ones were in Greece, Switzerland, Romania, Macedonia and Finland (below 10/100,000). Between 1997 and 2007, mortality from colorectal cancer decreased in many countries of western and northern Europe, particularly in women. In the EU overall, mortality from colorectal cancer declined between 1997 and 2007 from 19.7 to 17.4/100,000 men (−6% per quinquennium) and from 12.5 to 10.5/100,000 women (−8% per quinquennium). Mortality from colorectal cancer has been increasing in men—but not in women—from several countries from eastern Europe up to more recent years, but has been levelling off over the last decade in the Czech Republic, and over the last quinquennium in Hungary, Slovakia and in Spain, too. In 2007, there was still a substantial excess in colorectal cancer mortality in Slovakia, Hungary, Croatia, the Czech Republic and Slovenia in men (rates over 25/100,000), and in Hungary, Norway, Denmark and Slovakia in women (rates over 14/100,000). The lowest mortality rates were in Greece, Iceland and Finland for men (below 12/100,000), and in Greece, Finland and Switzerland for women (around 8/100,000). Most other European countries had mortality rates between 15 and 20/100,000 men and between 9 and 14/100,000 women.

Table 1. Overall age-adjusted1 mortality rates from colorectal cancer per 100,000 men and women in various European countries and in the European Union (EU) around 1997 (1995–99), 2002 (2000–04) and in 2007 (unless mentioned in parentheses)
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Table 2 gives corresponding rates and number of deaths from colorectal cancer for the population aged 30 to 49 years. Colorectal cancer rates at age 30–49 years were between 3 and 5/100,000 in most large European countries in both sexes (though higher in men) and tended to decline between 1997 and 2007. As for all ages, rates were higher and trends were less favorable in eastern Europe, including Hungary (over 9/100,000 men, and over 6/100,000 women), Bulgaria, the Czech Republic (with, however, a decline in men to 4.4/100,000 in 2007) and Slovakia. In the EU as a whole, colorectal cancer mortality at age 30 to 49 declined from 4.8 in 1997 to 3.9/100,000 in 2007 for men, and from 4.1 to 3.3/100,000 in women, i.e., about 10% per quinquennium.

Table 2. Age-adjusted1 mortality rates from colorectal cancer per 100,000 men and women aged 30–49 in various European countries and in the European Union (EU) around 1997 (1995–99), 2002 (2000–2004) and in 2007 (unless mentioned in parentheses)
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Corresponding figures for colorectal cancer mortality at age 50 to 69 years are given in Table 3. The overall decline in the EU was from 55.8/100,000 in 1997 to 47.8 in 2007 for men and from 33.2/100,000 to 28.5 for women, i.e. about 7% per quinquennium. Male rates were above 100/100,000, with little tendency to decline, in Hungary and Slovakia, and also above 100/100,000 up to 2002 in the Czech Republic, but declined to 83.4 in 2007. The highest female rates (40 to 50/100,000) were also in Hungary and Slovakia, but trends in middle-age women were more favorable than in men.

Table 3. Age-adjusted1 mortality rates from colorectal cancer per 100,000 men and women aged 50–69 in various European countries and in the European Union (EU) around 1997 (1995–99), 2002 (2000–04) and in 2007 (unless mentioned in parentheses)
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Table 4 considers colorectal cancer mortality at age 70 years and over. The overall decline in the EU was from 239/100,000 men in 1997 to 217 in 2007 (i.e., less than 5% per quinquennium) and from 153/100,000 women to 128 (over 8% per quinquennium). Again, the highest rates (over 300/100,000 men and over 160/100,000 women) were in the Czech Republic and Hungary and Slovakia, with appreciable falls in both sexes in the last calendar quinquennium only. Among western European countries, comparatively low colorectal cancer rates in the older population were observed in Denmark and the Netherlands.

Table 4. Age-adjusted1 mortality rates from intestinal cancer per 100,000 men and women aged ≥70 in various European countries and in the European Union (EU) around 1997 (1995–99), 2002 (2000–04) and in 2007 (unless mentioned in parentheses)
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Table 5 and Figure 1 show the joinpoint analysis for colorectal cancer mortality in men and women from major European countries over the period 1970–2007, at all ages and truncated 30–49, 50–69 and ≥70 years. Mortality from colorectal cancer has been declining, since the early 1990s in France (by 1.7–1.8% in the last 10 years), Germany (by 1.9–2.1%), Italy (by 1.3–1.7%), the UK (by 1.4–1.6%) as well as in the Czech Republic (by 2.7–3.3%) in both sexes. In Hungary, Poland, Slovakia and Spain, mortality has been increasing up to the late 1990s/early 2000s, to decrease only over more recent calendar years (with more favorable patterns in women), while in the Russian Federation and Slovenia mortality has only been levelling off in the last years. In the EU, rates started to level off in men between 1992 and 2003, with stronger declines thereafter (AAPC = −2% over the last 5 years); in women, mortality has been already levelling off between 1980 and 1992, and declining after 1992, with a AAPC over the last 5 years of −1.6%. Colorectal cancer mortality rates showed earlier and more favorable patterns in the population aged 30–49 years for all major European countries, with the exception of Hungary; trends were similar to those for the overall population for middle-age men and women (age 50–69 years), and somewhat less favorable in the population over 70 years, particularly in men from Poland and from the Russian Federation.

Figure 1.

Joinpoint analysis for colorectal cancer mortality in men and women from selected European countries, 1970–2007, at all ages, 30–49 years, 50–60 years and 70 years or more. equation image, Men; equation image, Women.

Table 5. Joinpoint analysis for colorectal cancer in men and in women, at all ages and truncated at age 30–49, 50–69 and ≥70, in major European countries and in the European Union (EU), 1970–2007
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Discussion

The present updated analysis of colorectal cancer mortality in European countries showed persistent favorable trends over the last decade in most countries of western and northern Europe, not only in women—for whom there were generally earlier and stronger declines—but in men also. Trends were particularly favorable in the young population (aged 30–49 years), thus suggesting that further improvements in colorectal cancer mortality trends in the near future are likely.14 However, trends have been less favorable up to the early 2000s in some southern European countries (Spain), and mostly in eastern countries (Hungary, Slovakia but not the Czech Republic), with a tendency to level off or decrease only in most recent years, particularly in women and in the young population. Most of these countries are, however, still characterized by extremely high mortality rates. Colorectal cancer mortality remains increasing in Romania and the Russian Federation, which had low/medium colorectal mortality rates in the past.

The favorable trends for colorectal cancer mortality observed in most countries from western Europe, but also, more recently, in some eastern European countries, are partly or largely attributable to improvements in the detection (early diagnosis) and treatment (with a consequent higher survival from the disease). Recent favorable changes in dietary and lifestyle habits (i.e., a more varied diet in central and eastern Europe) may have also played a role, by reducing the incidence in colorectal cancer in those areas.15–17

The wider availability of faecal occult blood testing, colonoscopy or sigmoidoscopy—either within “opportunistic” screening or in more recently implemented organized population screening programs—have increased the possibility to detect and remove adenomatous polyps, as well as to identify early stage tumors, which have a better prognosis.18–20 The impact of screening on incidence (and consequently on mortality) is, however, difficult to interpret. Long-term screening programs have played a relevant role in reducing colorectal cancer incidence and mortality over the last two decades in the USA, where screening was introduced between the 1970s and the 1980s3, 19; short-term screenings—as those in many European countries, where only more recent programs have been implemented—may, however, have had a smaller impact on mortality.19, 21 Incidence from colorectal cancer has been modestly increasing over the last decades in men from various European countries, including Austria, Slovenia, Spain and the Czech Republic, while it has been levelling off or declining in men from other countries and in women from most European countries, with the exception of Spain.22

A general improvement in surgical techniques for localized tumors, as well as a wider adoption of new treatment protocols and adjuvant therapies, including progressive increase in adjuvant chemotherapy for advanced nonlocalized tumors, and preoperative radiotherapy for rectal cancers, may have favorably influenced colorectal mortality.20, 23–26

As a consequence of early diagnosis and better treatment, progresses in survival from colorectal cancer mortality have been observed in European countries over the last decades, with an overall increase in 5-year relative survival in Europe from 45% in 1988–90 to 55% in 1997–99 in both sexes.27, 28 There are, however, still large between-countries differences, with general smaller progress and lower survival in countries from eastern Europe as compared to those of western and northern Europe. More limited resources in eastern European countries, as compared to longstanding economically developed countries of western and northern Europe, may explain the less favorable survival and mortality patterns in colorectal cancer in those countries.17, 19 Similarly, recent improvements in diagnosis and treatment may be responsible for the favorable changes in colorectal mortality in Spain over the last calendar years.29, 30

Recent favorable changes in diet—which account for a substantial proportion of colorectal cancers31, 32—with adoption of a more varied diet, richer in fruit and vegetables in more affluent populations, as recommended as a measure of cancer prevention in the last decades,33 may have also contributed to the declines in colorectal cancer mortality in various European countries (including central and eastern ones), by reducing the incidence of this neoplasm, particularly in women and in the young.15, 16, 22

Alcohol drinking and tobacco smoking have also been associated to colorectal cancer risk,34 and the reduction in the consumption of alcohol in several (southern) European countries,35 and in the prevalence of tobacco smoking, particularly in European men over the last decades may have favorably influenced the recent trends in colorectal cancer mortality.36

The earlier and more marked declines in colorectal cancer mortality in European women as compared to men, apart from earlier and more widespread favorable dietary and lifestyle habits,37 may also be due to the use of hormone replacement therapy (HRT) in menopause, as well as of other hormones, such as oral contraceptives (OC), particularly in countries of western and northern Europe, where HRT and OC have longer and more widely been used.38, 39 The more favorable mortality patterns in the young population could be attributed to earlier detection—with increased familial surveillance in young and middle-age adults—and advances in treatments, with better results among younger patients.40

Problems of reliability and validity of death certifications for colorectal cancer, which may vary across countries, calendar periods and age groups, should be considered in the interpretation of the observed trends. However, colorectal cancer is a major neoplasm, and diagnosis and certification of all intestinal sites, including colon and rectum, have long been sufficiently reliable41 and have not substantially changed in most European countries over the last decades. Moreover, no major changes in mortality rates were observed across subsequent Revisions of the ICD. The distinction between colon and rectal cancer poses some problems (since a large proportion of cancers arise in the recto-sigmoid junction) this cannot, however, have affected our estimates based on all intestinal cancers combined. Thus, it is unlikely that problems in diagnosis and certification practices may have meaningfully affected the observed colorectal cancer mortality trends in European countries.

In conclusion, decreases in colorectal mortality rates—most likely due to early diagnosis and/or improved treatment, as well as to improvements in dietary and lifestyle habits—have been observed in most western and northern European countries over the last decade, and more recently in countries of eastern Europe, too. However, high colorectal mortality rates are still registered in eastern European countries, and rates are still increasing in some of these countries, such as Romania42 and the Russian Federation. Thus, interventions to further reduce colorectal cancer burden—through wider adoption of screening programs, modern treatments and surgical procedures and improvements in diet and lifestyle habits—are required.43

Acknowledgements

This work was conducted with the contribution of the Italian and Swiss Leagues Against Cancer, the Swiss Foundation for Research Against Cancer and the Italian Association for Cancer Research. Paola Bertuccio was supported by a fellowship from the Italian Foundation for Cancer Research (FIRC). The authors thank Mrs I. Garimoldi for editorial assistance.

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