Keywords

2.1 Introduction

Colorectal cancer is still a major challenge in oncology. Population-based studies, which accurately record all cases diagnosed in a well-defined population and thus provide unbiased measurements, are the best way to assess changes in colorectal cancer frequency or survival. Worldwide incidence data are available from cancer registries, in particular through the successive volumes of Cancer Incidence in Five Continents covering registration up to 2012 [1,2,3]. For meaningful survival comparisons between countries or time periods, net survival is used. Net survival from cancer is the survival that would be observed if cancer were the only cause of death. This major epidemiological indicator allows thus comparisons without interference from other causes of death. Reliable survival rates are regularly published through international (CONCORD) [4,5,6] and European (EUROCARE) [7, 8] programs and using the French population-based cancer registries network (FRANCIM) [9,10,11] data. The aim of the present study was to provide updated temporal trends in colorectal cancer incidence and prognosis over the past decades.

2.2 Incidence

Last available worldwide data showed that colorectal cancer was the third most common cancer in men (746,000 cases, 10.0% of the total) and the second in women (614,000 cases, 9.2% of the total) in 2012 [12]. Differences in the incidence of colorectal cancers over the world are striking, with a tenfold variation between highest and lowest area, and geographical patterns are very similar in men and women (Fig. 2.1). Historically, the highest incidence rates have been reported in more developed countries. North America; Australia; New Zealand; Western Europe, including France; and Japan were considered high-risk incidence countries. Colorectal cancer was scarce in South America, China, or Africa. Other countries, mainly Northern, Southern, and Eastern Europe, were considered as middle-risk area. Starting from the mid-1990s, incidence rates declined for both sexes (Fig. 2.2) in the high-risk countries whereas slightly increased in most middle-risk ones (Denmark, Italy, Spain, or the Netherlands) and remained relatively stable in Switzerland and the UK. In contrast, increasing trends have been seen in developing countries. In the last worldwide published monography covering the 2008–2012 time period, European countries exhibited similar incidence rates as the USA and North America, whereas Eastern Europe and Japan had the highest rates. In France, incidence slightly decreased from the early 2000s with a mean annual decreased of −0.3% in men and in women between 2005 and 2012. The cumulative risk decreased from 2.0% for men born around 1920 to 0.9% for those born around 1950, a more than twofold increase. The corresponding values in women were 0.1% and 0.2%. Estimated world standardized incidence rates in 2015 are 37.0 per 100,000 inhabitants in men 23.6 per 100,000 in women. Through the GLOBOCAN database, the effects of demographic changes on the expected number of new cancer cases in different regions can be estimated (Fig. 2.3). Overall, nearly 1,700,000 new cases are predicted worldwide in 2020.

Fig. 2.1
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Worldwide colorectal cancer incidence—GLOBOCAN 2012, International Agency for Research on Cancer IARC

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Fig. 2.2
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Time trends in incidence of colorectal cancer (International Agency for Research on Cancer (IARC). Cancer Incidence in Five Continents monographies)

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Fig. 2.3
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Expected changes in incidence of colorectal cancer between 2012 and 2020, due to demographic changes in Europe and in the World. GLOBOCAN 2012, International Agency for Research on Cancer IARC. Numbers are computed using age-specific rates and corresponding populations for ten age-groups

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In contrast to this overall decreasing trend, the incidence of colorectal cancer has appeared to be increasing in male and female young adults under age 50 years in the USA, Canada, Australia, and New Zealand [13,14,15,16]. This trend is not described in European data. Reasons for explaining this trend are unclear or speculative. The measure of the role of established risk factors such as smoking, sedentary lifestyle, and diet in this population required dedicated epidemiologic research.

2.3 Survival

Results from the 65 countries involved in the CONCORD program comparing data from population-based registries show wide variations in survival from colorectal cancer (Fig. 2.4). For patients diagnosed with colon or rectal cancer during 2010–2014, 5-year net survival was higher than 60% in Australia, Canada, the USA, Japan, and New Zealand. In Europe, survival was as high in Northern (Denmark, Finland, Iceland, Ireland, Norway, Sweden, the UK), Southern (Italy, Portugal, Slovenia, Spain), and Western countries (Belgium, France, Germany, the Netherlands, Switzerland). For colon cancer, survival ranged from 50% to 60% in Central and South America, in China, and in Eastern Europe such as Estonia, Lithuania, the Czech Republic, Poland, and Slovakia. Survival was less than 50% in Colombia and India. For rectal cancer, survival ranged from 50% to 60% in Central and South America, in China, in Estonia, and in the Czech Republic and was less than 50% in Slovakia, Poland, Croatia, and India.

Fig. 2.4
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Five-year net survival of colorectal cancer. Cancer survival 2000–2014, CONCORD-3 program

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Through the CONCORD program, a high-resolution study was set up among colorectal cancer cases diagnosed during 1996–1998, in order to explain the difference in 5-year net survival observed between the USA and Europe [4]. Age-standardized survival was quite similar in the USA and Northern and Western Europe (around 54–58%) while lowest in Southern Europe (49%) and in Eastern Europe (42%). The transatlantic difference in survival was attributed to an earlier stage at diagnosis, a higher frequency of surgery, and use of adjuvant treatments in the USA.

Taking into account bowel location, European mean age-standardized 5-year relative survival was 57% after colon cancer and 56% after rectal cancer [8]. There were negligible differences between the sexes for colon cancer, but survival was higher for women than for men for rectal cancer. In all European regions, survival was best for patients aged 15–44 years, roughly constant for those aged 45–64 years, and decreased thereafter for colon cancer, whereas there were smooth age differences up to 74 years with a substantial drop thereafter in rectal cancer.

According to time period, survival varied little between 1995 and 1999 and 2000–2014 [6]. For colon cancer, it mostly flatted, with an increase less than 10% in Canada, Australia, Japan, Estonia, Finland, Lithuania, Sweden, Italy, France, and the Netherlands. It was more than 10% in China, Denmark, Norway, the UK, Portugal, Slovenia, Spain, the Czech Republic, Poland, and Switzerland. For rectal cancer, time trend did not vary in Japan, France, Italy, and New Zealand, whereas it was more marked, with a 10–20% increase in Australia, Canada, Denmark, Estonia, the UK, Portugal, Spain, the Czech Republic, Poland, the Netherlands, and Switzerland. Increase in 5-year relative survival was about 20% or more in China and Slovenia.

2.4 Risk Factors for Colorectal Cancer

Three risk’s levels are identified for colorectal cancer according to personal or familial past history:

  • Individuals with middle risk: men and women aged 50 and more. More than 90% of colorectal cancer cases are diagnosed after this age [17]. The median age at diagnosis for colon cancer, 69 in men and 73 in women, is older than that of rectal cancer, which is 63 in men and 65 in women [18].

  • Individuals with high risk:

    1. 1.

      First-degree relatives of patients with common colorectal cancer or with a large adenoma (>1 cm) have an increased risk of colorectal cancer when occurred before 60 years, or two first-degree relatives of patients with common colorectal cancer or with a large adenoma (>1 cm) have an increased risk of colorectal cancer irrespective of age.

    2. 2.

      Personal past history of colorectal cancer or large adenoma.

    3. 3.

      Personal history of chronic gastrointestinal inflammatory bowel disease (ulcerative colitis and Crohn’s disease).

  • Individuals with very high risk: familial adenomatosis polyposis and hereditary nonpolyposis colorectal cancer (Lynch syndrome).

2.4.1 Environmental Risk Factors

Based on solid evidence from the published literature, these factors include excessive alcohol intake, smoking, and excess body weight. A sedentary behavior has been also associated with an increased risk of colorectal cancer [19, 20]. Conversely, high levels of physical activity are associated with a lower risk of colon cancer with a reported risk reduction of approximately 25% [21]. Such a relationship has not been established for rectal cancer [21]. Other modifiable risk factors that have been convincingly associated with higher colorectal cancer risk are the consumption of red and processed meat [22]. The findings for some risk factors suggest sex differences and/or sub-site variations. Additionally, some studies show a dose-response association. Table 2.1 summarizes the results of each environmental risk factor mentioned above from recent and large meta-analyses.

Table 2.1 Environmental and lifestyle risk factors for colorectal cancer
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2.4.2 Personal or Familial History of Adenoma or Colorectal Cancer

Results from population-based studies and meta-analyses showed that the risk of developing colorectal cancer is about two times higher in persons with at least one affected first-degree relative than in those without family history. The risk of colorectal cancer is more than threefold higher among persons with a first-degree relative diagnosed under age 50 (pooled relative risk (RR) from meta-analysis = 3.55; 95% confidence interval = 1.84–6.83) and between two- and threefold higher if a first-degree relative is diagnosed under the age of 60 (RR range = 1.81–3.30). The risk of colorectal cancer associated with having a first-degree relative with an adenoma is less than 2 (RR range = 1.3–51.99). The risk of colorectal cancer is higher if the adenoma was ‘large’ (>10 mm; RR = 1.68; 1.29–2.18) or ‘advanced’ (with villous histology; RR = 3.90; 0.89–17.01) and if the first-degree relative is diagnosed with an adenoma under age 60 (RR range: 1.41–1.54) [27].

2.4.3 Inflammatory Bowel Diseases: Ulcerative Colitis and Crohn’s Disease

Several meta-analyses of population-based studies quantified the over-risk of colorectal cancer associated with ulcerative colitis and Crohn’s disease (RR from 1.7 to 21.6). The variation of over-risk is attributable to the age of onset of the disease, extent of the disease (pancolitis is associated with a 10–15-fold excess risk), intensity of inflammation, concomitant primary sclerosing management, and familial history of colorectal cancer. The incidence of colorectal cancer, in this population with inflammatory bowel diseases, is from 0.5 to 12.4/100,000 persons-years between 0 and 10 years of follow-up, from 1.4 to 11.5 between 10 and 20 years, and between 2.4 and 44.9 after 20 years [28].

2.4.4 Genetic Mutation

High-risk mutations in known colorectal cancer susceptibility genes are involved in 5–10% of colorectal cancer cases [29]. Two dominantly inheritant syndromes are described: the familial adenomatosis polyposis (APC adenomatous polyposis coli gene; <1% of colorectal cancer cases) and the hereditary nonpolyposis colorectal cancer (Lynch syndrome with several mutations in mismatch repair genes; roughly 5% of colorectal cancer cases). In both of these syndromes, the mean age of onset of colorectal cancer is much smaller (less than 50 years old) than in sporadic colorectal cancers, and extracolonic malignancies are also observed. The prevalence of Lynch syndrome varies according to studies. Recently, using data from the international Colon Cancer Family Registry, the prevalence of Lynch syndrome was estimated at 1 in 279 of the population [30]. The overall hazard ratio for colorectal cancer in carriers of Lynch syndrome decreased with each additional decade of life, from 135 (95%CI, 112–165) for men and 99 (95%CI, 79–125) for women when in their 30s to 4.0 (95%CI, 2.8–5.7), respectively, when in their 70s [31].

2.5 Emergency Presentation with Colorectal Cancer: Frequency and Risk Factors

Studies examining risk factors and circumstances surrounding emergency colorectal cancer diagnosis are limited. Incidence of obstructing and perforated colorectal cancers is variously estimated in the literature, from 8% to 40% due to varying definition, from sub-occlusion to the necessity of emergency surgery. Using a strict definition of obstruction through population-based studies, approximately, 10% will occur in an emergency context because of obstruction, and less than 5% because of perforation [32,33,34].

Two large database studies [34, 35] have found that patients with advanced age (adjusted odds ratios, aORper 10 years increment = 1.19; 95% confidence interval, 1.16–1.22 [34], and aOR80 years vs. 70 years = 1.49; 1.47–1.52 [35]), women (aOR = 1.08; 1.01–1.14 and 1.12; 1.08–1.16, respectively), and patients with lower income (aORlowest vs. highest = 1.28; 1.18–1.39) [34] or higher socioeconomic deprivation (aORmost vs. least deprived = 1.54; 1.45–1.64) [35] and comorbidities are significantly associated with emergency presentation. In the Canadian population-based study, which included 41,356 patients (7739 emergency presentations), Rabeneck et al. [34] reported that lack of a regular source of a family physician (aOR = 1.43; 1.30–1.54) and not having a previous bowel evaluation (aOR = 1.45; 1.33–1.59) were additionally associated with colorectal cancer emergencies and consistent with other studies [36,37,38]. In their large study of over 90,000 patients, Wallace and colleagues found that ethnicity had an impact on the risk of an emergency admission for colorectal cancer, with higher risk for nonwhite patients (aOR = 1.13; 1.02–1.24) [35]. The most recent systematic review by Mitchell et al. [39] identified 19 studies that considered factors associated with diagnosis of colorectal cancer in the context of an emergency presentation and found older age to be a strong significant factor in the majority of the studies analyzed, with aOR varying from 1.19 to 5.85. Results for the other risk factors were less conclusive. Evidence regarding symptoms before emergency cancer diagnosis is still limited. Abdominal pain, constipation, weight loss, and diarrhea are the preceding symptoms more generally associated with an increased risk of emergency presentation [39,40,41,42].

2.6 Conclusion

Colorectal cancer is the third most common cancer in men and the second in women worldwide (2012). Starting from the mid-1990s, incidence rates decline for both sexes in the high-risk countries (mostly developed countries) whereas increase in most middle-risk ones (mostly developing countries). Five-year net colorectal cancer survival varies from 35% to 75%. Survival varies little between 1995 and 1999 and 2000–2014. The main risk factors for colorectal cancer are environmental factors (obesity, tobacco use, alcohol intake, sedentary behavior, and consumption of red and processed meat), inflammatory bowel disease (ulcerative colitis and Crohn’s disease), family or personal history of colorectal cancer or large adenoma, and inherited genetic factors (familial adenomatosis polyposis and hereditary nonpolyposis colorectal cancer). Colorectal cancer diagnosis occurs in an emergency context in about 10% because of obstruction and less than 5% because of perforation particularly in older patients, women, and patients with socioeconomic deprivation and comorbidities.