WeBSurg, the e-surgical reference of Laparoscopic surgery

WebSurg is a free virtual surgical university, accessible worldwide through the Internet. Our goal is to provide surgeons, scientific societies and the medical industry with the first online continuing medical education in laparoscopic surgery and information on the latest developments in laparoscopic surgery, including NOTES and robotics.

Browse the WORLD
Virtual University
English ▼

EPIDEMIOLOGY OF COLORECTAL CANCER




G Launoy, MD, Registre des tumeurs digestives du Calvados, Caen, Equipe associée INSERM/InVS, France




1. Incidence

2. Temporal trends

3. Risk groups

4. Risk factors

5. References


1. Incidence of colorectal cancer worldwide

Colorectal cancer is the fourth most common cancer worldwide. More than two thirds of new cases occur in developed countries, where colorectal cancer ranks as the second most frequent form of cancer for all genders ( Parkin et al. , 1993 ). The highest incidences are found in the United States, Canada and Oceania. In these regions, registered annual incidence is often higher in the male population, at more than 40 per 100 000 inhabitants, and from 30 to 40 per 100 000 inhabitants in the female population. In the United States and Canada, when the population group is determined, the incidence is usually higher in African-Americans than in Caucasians. The lowest incidence rates (less than 10 per 100 000 inhabitants) are found in Africa, South America and Asia, except in Japan, where there is a very high incidence in men. The incidence rates in European countries are in between those of North America and the other continents, with eastern and southern European countries having the lowest incidences.
Figure
Figure 1.a
Incidence of colorectal cancer in men worldwide ( Parkin et al., 1997 )

Rectal cancer demonstrates significantly lower rates of geographical variation; some northern European countries have the same risk of rectal cancer as the United States and Canada.
Within each country, cancer risk varies according to ethnic and socio-demographic features. The highest incidences are almost always found in Caucasians, either in their native countries or in their host countries. For example, in Zimbabwe, the incidence is 4 times higher in Europeans than in Africans. Studies conducted in Hawaii showed that the risk level of descendants of immigrants becomes, over generations, similar to that of the native inhabitants ( Kolonel et al. , 1986 ).
In Europe, the incidence of colorectal cancer increases at a steep gradient from the south to the north, both in men and women.
Figure
Figure 1.b
Figure
Figure 1.c




1. Incidence

2. Temporal trends

3. Risk groups

4. Risk factors

5. References


2. Temporal trends of colorectal cancer worldwide

Mortality data from studies performed on colorectal cancer trends in various regions of the world must be analyzed cautiously. Indeed, a change in specific mortality in a given region can either reflect a modification in the management of this type of cancer (access to care, diagnosis, and treatment) or be secondary to an actual change in cancer frequency. Incidence data obtained from population studies are therefore important to the interpretation of mortality data.
According to data from the International Agency for Research on Cancer (Lyon), there has been a general trend toward an increase in colorectal cancer frequency over the last decades in Europe as well as in most developed countries ( Coleman et al. , 1993 ). This increase has been the highest in Japan. In the United States, the increase has been slowing down since the 1980s in the overall population but has remained markedly elevated amongst African Americans ( Chow et al ., 1991 ). In Europe, there has been a marked increase in the incidence of colorectal cancer in eastern countries and some southern countries such as Spain. On the other hand, the incidence has been stable in northern European countries ( Jensen et al. , 1990). In France, the increase in the incidence of colorectal cancer has been moderate.

The analysis of data from the earliest register in the world (Connecticut, United States) shows that such incidence trends vary depending on gender and location of the tumor. In males, the increase in the incidence rate has been limited to colon cancer, whereas rectal cancer rates have remained stable. In females, the increase in the incidence rate has only occurred in cases of proximal colonic tumors. In Europe, data are more scattered in time and location, but the same phenomena are observed, with the exception of rectal cancer, whose incidence is decreasing in Switzerland and Northern Ireland ( Kee et al. , 1992; Levi et al. ,1993 ). The concordance of such observations throughout various parts of the world suggests that the data reflect a real change in the frequency of this type of cancer in intermediate and high risk regions of the world rather than trends due to changes in registration techniques:
  • increase in the incidence of cancer of the proximal colon;
  • stability or moderate increase in the incidence of cancer of the distal colon;
  • decrease in the incidence of rectal cancer.
These studies have revealed a redistribution of the incidence of colon cancer according to the area of colon affected. This accounts for the increase in the proportion of proximal cancers (ascending colon and transverse colon) ( Kee et al. , 1992 ).




1. Incidence

2. Temporal trends

3. Risk groups

4. Risk factors

5. References


3. Risk groups related to family history

Family history of cancer is associated with an increased risk of colorectal cancer compared to the general population. In some cases, distinct inherited syndromes have been defined, and the involved genes have been identified. In the other cases, genetic causes have not been clearly determined and there is a probable involvement of several genes, interacting with environmental factors.

3.1. Familial adenomatous polyposis (FAP)

This pathology is currently the best studied genetic predisposition for colon cancer. It is due to mutations of the APC gene on chromosome 5. Its autosomal dominant mode of inheritance has been known for a long time. The disease is characterized by the presence of at least 100 colonic adenomas. More than 90% of patients with FAP develop colon cancer by age 40 if prophylactic colectomy is not performed. The prevalence of this disease is extremely low (about 1 in 10 000 people), accounting for less than 1% of colorectal cancers ( Fearon, 1992 ).
Figure
Figure 3.1
Pedunculated colonic polyp

3.2. Hereditary non-polyposis colorectal cancer (HNPCC) syndrome

Familial forms of colorectal cancer without underlying polyposis have been described for a long time. They are characterized by the onset of cancer at a young age and by a high risk of other associated digestive cancers (stomach, small bowel, and pancreas) or genitourinary cancers (ovarian, endometrial, urinary tract). The genes involved are numerous and they play an active role in DNA repair. In order to study the HNPCC syndrome despite its polymorphism, strict inclusion criteria known as the Amsterdam criteria have been proposed:
  • At least 3 family members have had colorectal cancer, one of whom is a first-degree relative of the others;
  • At least 2 generations are affected;
  • Colorectal cancer was diagnosed for at least 1 family member before the age of 50 years.
Thus defined, these cancers represent 1% to 6% of colorectal cancers as reported in the literature.

3.3. Family history of other forms of colorectal cancer

Familial adenomatous polyposis and hereditary non-polyposis colorectal cancer represent at the very most 5-10% of all colorectal cancers. Nevertheless, a positive family history is found in 10% to 20% of colorectal cancers. The increased risk of cancer associated with the presence of cancer in a first-degree relative varies from 1.8 to 8 (with 1 corresponding to the risk of cancer in the rest of the population) according to studies ( Burt, 1996 ). Among these studies, those performed in presumably unselected population groups which provide the lowest relative risks should most likely be retained. In all studies, the relative risk increases with the number of family members affected by cancer and if their cancer was diagnosed at a young age.

3.4. Family history of colorectal adenoma

Several case studies suggest that the risk of colorectal cancer is higher for individuals who have a family member with adenomatous polyps, just as the risk of adenoma increases in relatives of persons who have had colorectal cancer. One study suggests that the higher risk is limited to adenomas measuring 1 cm and larger ( Bonelli et al ., 1988; Bazolli et al. , 1995 ).




1. Incidence

2. Temporal trends

3. Risk groups

4. Risk factors

5. References


4. Risk factors

Colorectal cancer is one of the forms of cancer whose risk factors have been studied most thoroughly. Contrary to certain other types of cancer, there is no single environmental factor whose elimination will result in a significant decrease in the incidence of colorectal cancer. Just as various genetic alterations have been linked to tumor development in colorectal cancer, various environmental risk factors have been identified that play a part in the development of adenomatous polyps or their transformation into carcinomas.
Figure
Figure 4
Stained section of a tubulovillous colonic adenoma
1. Pedicle
2. Normal mucosa
3. Adenomatous proliferation

4.1. Diet

The protective factor of vegetable consumption is the least controversial hypothesis ( Potter et al. , 1993; Trock et al. , 1990 ). This protective effect is more cited in colon cancer than for rectal cancer and for raw vegetables rather than cooked vegetable consumption. The protection seems to be conferred by the fiber content of the vegetables consumed ( Howe et al. , 1992 ).

A high consumption of meat and fat is the risk factor most often implicated for both colon cancer and adenomas. A high consumption of eggs also appears as a risk factor in most studies ( Potter et al. , 1993 ).

High fat consumption is usually correlated with obesity and lack of physical exercise, especially in North American studies. These 3 risk factors are related and it is often difficult, in the absence of strong pathophysiological evidence, to isolate the most relevant risk factor. An association of colorectal cancer risk with overall calorie intake has been found in most case studies ( Little et al. , 1993; Neugut et al. , 1991 ). The benefit of physical exercise is considered to be the most important protective factor by the most recent studies ( Potter et al. , 1993; Giacosa et al. , 1999; Lee et al ., 1991 ).
For methodological reasons, studies based on the influence of nutrients are more difficult to carry out than studies based on the influence of diet. This is mainly due to the difficulties in accounting for the variability of the nutrient content in food depending on the product’s origin, and how it is preserved and cooked. Consequently, food conversion charts are very different from one country to another. Despite all these difficulties, the protection provided by nutrients such as calcium and vitamin D is still controversial. In a recent European study, calcium supplements were associated with a modest but insignificant decrease in polyp recurrence ( Bonithon-Kopp et al. , 2000 ). In the same study, fiber supplementation was shown to have an adverse affect.

4.2. Alcohol

Though there is little data in support of a direct etiologic role of alcohol consumption on the incidence of colon cancer, a specific association between the risk of rectal cancer and beer consumption is evidenced by most studies ( Kune and Vitetta, 1992; Longnecker et al ., 1990 ). If there is an association between alcohol consumption and the risk of colorectal cancer, the relative risk is very low. In 1990, a meta-analysis found the relative risk associated with a 24 g consumption of alcohol per day at 1.10 for any type of alcohol (95% confidence interval: 1.05 -1.14) and at 1.26 (1.13 -1.41) for beer ( Longnecker et al. , 1990 ).

4.3. Smoking

An American cohort study recently showed that tobacco consumption was significantly associated with an increased risk of adenoma formation in both men and women and with an increased risk of colon cancer in men ( Giovannucci et al ., 1994 a , Giovannucci et al ., 1994 b ). This refutes most earlier case studies which demonstrated no association with tobacco consumption. The major finding of this study was the demonstration that smoking increased risk of cancer after 35 years of tobacco consumption, while it was related to the risk of small adenoma occurrence within the first 20 years, and with the risk of large adenoma occurrence after 20 years. The association was more evident in men than in women and for colon cancer than for rectal cancer.

4.4. Occupational exposure

Few studies have examined occupational exposure hazards as a risk factor for colon and rectal cancer. Particular fields of interest include the automobile industry, and occupations involving wood work, metal work, printing and painting ( Williams et al. , 1977; Brownson et al. , 1989; Gallagher and Threfall, 1983 ). The role of exposure to asbestos has been cited several times, for all digestive cancers, or specifically in colorectal cancer ( Selikoff et al. , 1979; Fredriksson et al. , 1989; De la Provôté et al ., 2000 ).

4.5. Interaction genes-environment

In the years to come, our understanding of the etiology of colorectal cancers will be enriched by several classically designed epidemiologic studies (case-control, cohort studies) which will collect data on both the environment (diet, occupational exposure, smoking, alcohol, etc.) and biomarkers in blood or urine samples. These studies will search for individual sensitive markers, and will be the basis for analysis of the role of genetic polymorphisms in enzymes intervening in the metabolism of numerous potentially carcinogenic xenobiotics. As an example, Le Marchand demonstrated the interaction between eating well-done red meat and certain NAT2 and CYP1A2 polymorphisms ( Marchand, 1999 ) in order to account for the rapid increase in the incidence of colorectal cancer in the Japanese population migrating to Hawaii.




1. Incidence

2. Temporal trends

3. Risk groups

4. Risk factors

5. References


5. References

  1. Bazzoli F, Fossi S, Sottili S, Pozzato P, Zagari RM, Morelli MC et al. The risk of adenomatous polyps in asymptomatic first-degree relatives of persons with colon cancer. Gastroenterology 1995;109:783-8.
  2. Bonelli L, Martines H, Conio M, Bruzzi P, Aste H. Family history of colorectal cancer as a risk factor for benign and malignant tumours of the large bowel. A case-control study. Int J Cancer 1988;41:513-7.
  3. Bonithon-Kopp C, Kronborg O, Giacosa A, Rath U, Faivre J. Calcium and fibre supplementation in prevention of colorectal adenoma recurrence: a randomised intervention trial. European Cancer Prevention Organisation Study Group. Lancet 2000;356:1300-6.
  4. Brownson RC, Zahm SH, Chang JC, Blair A. Occupational risk of colon cancer. An analysis by anatomic subsite. Am J Epidemiol 1989;130:675-87.
  5. Burt RW. Familial risk and colon cancer. Int J Cancer 1996;69:44-6.
  6. Chow WH, Devesa SS, Blot WJ. Colon cancer incidence: recent trends in the United States. Cancer Causes Control 1991;2:419-25.
  7. Coleman MP, Esteve J, Damiecki P, Arslan A, Renard H. Trends in cancer incidence and mortality. IARC Sci Publ 1993;121:1-806.
  8. De La Provôté S, Desoubeaux N, Paris C, Raffaelli C, Galateau-Salle F, Letourneux M et al. Le dépistage du cancer colorectal chez les personnes exposées professionnellement à l'amiante. Gastroenterol Clin Biol 2000;24:637.
  9. Fearon ER. Genetic alterations underlying colorectal tumorigenesis. Cancer Surv 1992;12:119-36.
  10. Fredriksson M, Bengtsson NO, Hardell L, Axelson O. Colon cancer, physical activity, and occupational exposures. A case- control study. Cancer 1989;63:1838-42.
  11. Gallagher RP, Threlfall WJ. Cancer mortality in metal workers. Can Med Assoc J 1983;129:1191-4.
  12. Giacosa A, Franceschi S, La Vecchia C, Favero A, Andreatta R. Energy intake, overweight, physical exercise and colorectal cancer risk. Eur J Cancer Prev 1999;8 Suppl 1:S53-60.
  13. Giovannucci E, Colditz GA, Stampfer MJ, Hunter D, Rosner BA, Willett WC et al. A prospective study of cigarette smoking and risk of colorectal adenoma and colorectal cancer in U.S. women. J Natl Cancer Inst 1994a;86:192-9.
  14. Giovannucci E, Rimm EB, Stampfer MJ, Colditz GA, Ascherio A, Kearney J et al. A prospective study of cigarette smoking and risk of colorectal adenoma and colorectal cancer in U.S. men. J Natl Cancer Inst 1994b;86:183-91.
  15. Howe GR, Benito E, Castelleto R, Cornee J, Esteve J, Gallagher RP et al. Dietary intake of fiber and decreased risk of cancers of the colon and rectum: evidence from the combined analysis of 13 case-control studies. J Natl Cancer Inst 1992;84:1887-96.
  16. Jensen OM, Esteve J, Moller H, Renard H. Cancer in the European Community and its member states. Eur J Cancer 1990;26:1167-256.
  17. Kee F, Wilson RH, Gilliland R, Sloan JM, Rowlands BJ, Moorehead RJ. Changing site distribution of colorectal cancer. Bmj 1992;305:158.
  18. Kolonel LN , Hankin JH , Nomura AM . Multiethnic studies of diet, nutrition, and cancer in Hawaii . In: Hayashi Y, Nagao M, Sugiruma T, Takayama S, Tomatis L, Wattenberg LW, et al, editors. Diet, nutrition and cancer. Tokyo: Japan Sci Soc Press; 1986. p.29-40.
  19. Kune GA, Vitetta L. Alcohol consumption and the etiology of colorectal cancer: a review of the scientific evidence from 1957 to 1991. Nutr Cancer 1992;18:97-111.
  20. Lee IM, Paffenbarger RS, Jr., Hsieh C. Physical activity and risk of developing colorectal cancer among college alumni. J Natl Cancer Inst 1991;83:1324-9.
  21. Levi F, Randimbison L, La Vecchia C. Trends in subsite distribution of colorectal cancers and polyps from the Vaud Cancer Registry. Cancer 1993;72:46-50.
  22. Little J, Logan RF, Hawtin PG, Hardcastle JD, Turner ID. Colorectal adenomas and energy intake, body size and physical activity: a case-control study of subjects participating in the Nottingham faecal occult blood screening programme. Br J Cancer 1993;67:172-6.
  23. Longnecker MP, Orza MJ, Adams ME, Vioque J, Chalmers TC. A meta-analysis of alcoholic beverage consumption in relation to risk of colorectal cancer. Cancer Causes Control 1990;1:59-68.
  24. Marchand LL. Combined influence of genetic and dietary factors on colorectal cancer incidence in Japanese Americans. J Natl Cancer Inst Monogr 1999;26:101-5.
  25. Neugut AI, Lee WC, Garbowski GC, Waye JD, Forde KA, Treat MR et al. Obesity and colorectal adenomatous polyps. J Natl Cancer Inst 1991;83:359-61.
  26. Parkin DM, Pisani P, Ferlay J. Estimates of the worldwide incidence of eighteen major cancers in 1985. Int J Cancer 1993;54:594-606.
  27. Parkin DM, Whelan SL, Ferlay J, Raymond L, Young J. Cancer Incidence in Five Continents. IARC Sci Publ 1997; VII(143).
  28. Potter JD, Slattery ML, Bostick RM, Gapstur SM. Colon cancer: a review of the epidemiology. Epidemiol Rev 1993;15:499-545.
  29. Selikoff IJ, Hammond EC, Seidman H. Mortality experience of insulation workers in the United States and Canada, 1943--1976. Ann N Y Acad Sci 1979;330:91-116.
  30. Trock B, Lanza E, Greenwald P. Dietary fiber, vegetables, and colon cancer: critical review and meta- analyses of the epidemiologic evidence. J Natl Cancer Inst 1990;82:650-61.
  31. Williams RR, Stegens NL, Goldsmith JR. Associations of cancer site and type with occupation and industry from the Third National Cancer Survey Interview. J Natl Cancer Inst 1977;59:1147-85.