1. 1 Epidemiology and prevention of colorectal cancer ICD9: 153, 154

2. 2 1. Significance  The second leading cause of cancer death in men & women (The # 1 is..). It accounts for 10% of all cancer deaths in the USA.  More lives are lost each year to colorectal cancer than to breast cancer and AIDS combined.  it accounts for nearly half of the diagnosed new cases of cancer.  The incidence and mortality of colorectal cancer (CRC) show increasing tendency worldwide.  Compared to 2000 data, the new cases in 2007 approximate 1,200,000 and the death cases 630,000, a total increase of 27% and 28% and an annual increase of 3.9% and 4.0%, respectively.  The overall 5-year survival rate for CRC is 61%; 91% for CRC in local stage.

3. 3 2.Pathophysiology  Not well understood  Some research suggests delay transit of fecal material.  Related to:  Low fiber diet intake  Lack of physical activity  Predominant cell type is adenocarcinoma (96% of all cases).

4. 4 3.Descriptive epidemiology a.High-Risk Groups  Gender: 44% Higher for men  Race: 15% higher for Blacks than for Whites.  Age: Incidence rises sharply after the age of 50 years; >80% of diagnosed cases of colorectal cancer occur in patients older than 55 years.  The mean age at diagnosis is 62 years.  SES: People in higher socioeconomic groups.  Certain genetic and medical conditions Predispose to CRC include: First kin relatives Familial polyposis Inflamatory bowel disease (e.g. Ulcerative colotis, Crohn’s ).

5. 5 b.Geographic distribution  Worldwide,  CRC is highest in developed countries in North America, Northern and Western Europe, and New Zealand.  Extremely low in Japan; Japanese immigrants to the USA have similar rates as the Americans.  In USA, CRC is highest in Northeast and North-Central states, lowest in Western and Southwestern states.

6. 6 c.Time trends  T he incidence of CRC varies regionally and changes over the time. a.In previously identified high-incidence areas, there are three tendencies: The incidence keeps rising such as in UK, The incidence is stable such as in New Zealand, and The incidence tends to decrease such as in US and Western Europe. b.In previously identified low-incidence areas, the incidence of CRC is increasing, such as in Japan, Hong Kong, Singapore, Hungary, Poland, and Puerto-Rico, especially in Japan, where the incidence increases the fastest.

7. 7  Since 1991, the average increase in mortality of CRC is 4.7% every year.  The increasing number of female patients and the shift of the tumor location to the right side are also the trends noticed for CRC in recent years.

8. 8 4.Risk Factors a.Magnitude of risk factors Modifiable risk factors for colorectal cancer, US MagnitudeRisk FactorPop.Att.Risk (%) Strong RR>4None- Moderate RR 2-4None- Weak RR <2High fat-diet15-25 Low-vegetable diet25-35 Physical inactivity32 PossibleAlcohol Occupation (asbestos, wood dust, metals) Aspirin use (protective) Obesity Vitamin D deficiency smoking

9. 9  Relative Risk= Risk of disease/death in the exposed population Risk of disease/death in the unexposed population  Population Attributable Risk is: Proportion of a disease in a population that is associated (attributed to) a certain risk factor. b. Population – Attributable Risk Up to one-half of CRC may be related to diet. Within this proportion, it is estimated that 15%-25% of CRC may be related to fat intake and that 25%-35% may be related to low intake of fruits and vegetables An estimated 32% of CRC may be related to physical inactivity.

10. 10 5.Prevention and Control Measures a.Prevention The overwhelming evidence indicates that primary prevention of colon cancer is feasible. At least 70% of colon cancers may be preventable by moderate changes in diet and lifestyle. i. Diet and Nutrition  There is convincing evidence from epidemiological and experimental studies that dietary intake is an important etiological factor in colorectal neoplasia.  The precise mechanisms have not been clarified, yet several lifestyle factors have a major impact on colorectal cancer development. - Fats and meats US Nurses Health Study:  In 1990 Willett et al published the results from follow up of 88,751 women aged 34-59 years who were without cancer or inflammatory bowel disease at recruitment.

11. 11 Consumption of animal fat was found to be associated with increased risk of colon cancer, after adjustment for total energy intake. RR in the highest compared with the lowest quintile = 1.89 (95% confidence interval 1.13 to 3.15) (P=0.01). No association was found with vegetable fat. RR in women who ate beef, pork, or lamb as a main dish every day was 2.49 (1.24 to 5.03) compared with women reporting consumption less than once a month. The study data supported: - the hypothesis that a high intake of animal fat increases the risk of colon cancer, and - the existing recommendations to substitute fish and chicken for meats high in fat.

12. 12 - Fiber  Fiber has many components commonly grouped into: insoluble, non-degradable constituents (mainly found in cereal fiber) and soluble, degradable constituents, such as pectin and plant gums (mainly found in fruits and vegetables).  Epidemiological studies have reported differences in the effect of these components.  Many studies, however, found no protective effect of fiber in cereals but have consistently found a protective effect of fiber in vegetables and perhaps fruits.  This might reflect an association with other components of fruits and vegetables, with fiber intake acting merely as an indicator of consumption.  Recent epidemiologic studies tended not to support a strong influence of fiber; instead, some micronutrients or phytochemicals in fiber-rich foods may be important. Folate (and methionine) is one such nutrient that has received attention lately and is being studied in randomized intervention trials.

13. 13 International and migrant population data indicate that a substantial reduction in the incidence of CRC could be achieved in 10 years through dietary changes alone:  By increasing per capita consumption of fiber from fruits and vegetables to 20-30 grams/day.  By decreasing per capita consumption of fat to below 30% of total calories. ii.Vitamin D A scientific review of literature found that vitamin D was beneficial in preventing colorectal cancer. There is an inverse relationship with blood levels of 80 nmol/L or higher. These levels are associated with a 72% risk reduction compared with lower than 50 nmol/L levels. iii.Chemopreventive agents (aspirin and postmenopausal estrogens): There is much evidence suggesting an inverse relationship between aspirin or non-steroidal anti-inflammatory drug (NSAID) consumption and CRC incidence and mortality.

14. 14  However, NSAID consumption is not problem-free; 1997 data show 107,000 hospitalisations and 16,500 deaths due to NSAID consumption in the U.S. alone.  Therefore, drugs that have more acceptable side-effect profiles are required.  Cyclo-oxygenase (COX)-2-specific inhibitors, which have an improved safety profile, seem to be well-suited drug candidates for CRC prevention.  Pharmacology and genetics are collaborating to develop new chemoprevention agents designed to affect molecular targets linked to specific premalignant or predisposing conditions.

15. 15 iv.Physical inactivity, and to a lesser extent excess body weight, are consistent risk factors for colon cancer. v.Exposure to tobacco products early in life is associated with a higher risk of developing colorectal neoplasia.

16. 16 Screening for CRC The evidence is convincing that there are substantial benefits to screening in asymptomatic adults. U.S. Preventive Services Task Force (USPSTF) recommends screening for colorectal cancer in all asymptomatic adults from 50 to 75 years of age. Balancing the small benefit and potential increased harms, the USPSTF does not recommend routine screening in asymptomatic adults from 75 to 85 years of age and recommends against screening in asymptomatic adults older than 85 years of age who have previously been adequately screened.

17. 17 screening for colorectal cancer with:  High-sensitivity fecal occult blood testing (fecal DNA and fecal immunochemical testing)  sigmoidoscopy, or  colonoscopy Modeling evidence suggests that population screening programs between the ages of 50 and 75 years using any of the following 3 regimens will be approximately equally effective in life-years gained, assuming 100% adherence to the same regimen for that period.

18. 18 1)annual high-sensitivity fecal occult blood testing, This strategy, (sensitivity for cancer ≥70%) that has a false-positive rate less than 10% (that is, specificity >90%), is estimated to require the fewest colonoscopies while achieving a gain in life-years similar to that seen with screening colonoscopy every 10 years 2)sigmoidoscopy every 5 years combined with high-sensitivity fecal occult blood testing every 3 years, and 3)screening colonoscopy at intervals of 10 years.