Colon Cancer Energetics

Colon & Rectum

Statistics:

In the US, in 2011 141,200 people will be diagnosed with colon cancer. And about 49,380 will die from the disease. These are sobering statistics for the third most common cancer that afflicts people in the United States. Around the globe 610,000 deaths are attributed to colo-rectal cancer annually.

Location of Cancer:

72% are located in the Colon

28% in the Rectum

Biology:

96% of all colon cancers are adenocarcinomas. The growth of the cancer is a non-random linear progression. By that is meant it progresses from one state to another in serial uniformity. The process takes many years and by some calculations it can take between 10-15 years. These cellular dynamics indicate that there are plenty of opportunities to detect and protect people from this disease with early intervention.

Polyp into a Cancer

Interestingly the cellular dynamics that lead to colon cancer seem to have a genetic trigger. This trigger is usually present in the most terminal layer of the colon crypt cells. This genetic trigger mechanism can be a tumor suppressor gene or a proto-oncogene. Mutation of the tumor suppressor gene makes it unable to protect against an uncontrolled proliferation of cells as happens with the APC gene. The APC gene codes for a protein that is involved in restrained cellular growth of the cell. 

The APC gene is present on the long arm of Chromosome 5 at position 21-22 (5q21-22). 40% of people who carry the APC gene mutation and have Familial Adenomatous Polyposis Coli (FAP) have a100% chance of developing colon cancer by age 40.

Large Adenomatous Polyps

Since the process of cancer is linear, it requires other mutations to occur in the genetic structure of the precancerous cells before a full-blown cancer forms and these include DCC gene mutation, p53 mutation and others. If a single gene mutates without corresponding future mutations to move the story forward the net result can be a large adenomatous polyp (Stuck in the first gear – auto analogy) On the other hand if rapid sequential genetic mutations are written out on the DNA script, then a fairly small size cancerous tumor (sometime undetectable) can have disseminated metastases. Genes thus apply the breaks or press the accelerator in sequence and infrequently at the same time.

There is ample data in the medical literature that migrants assume risk of their destination. And studies of the  American Indians (AI) and Alaskan Natives (AN) living in Alaska have shown a 102/100,000 incidence of colon cancer versus 21/100,000 for AI/AN living in the Southwestern US.  So migratory patterns conforming to the destinations play a part in the risk factors. In other words the dietary habits, consumption of foods and exercise have a proximate bearing on the biological incidence.

Racial Disparities Incidence:

Race/ Ethnicity	Men %	Women %
Non-Hispanic White	56.8	41.9
Non-Hispanic Black	68.3	51.6
Asian American/Pacific	42.8	32.5
American Indian/Alaskan	43.2	34.4
Hispanic/Latino	49.2	36.8

Risk Factors: Overall:

1. Age: Individuals older than 50 years are at risk. The lifetime risk is 1 in 20 or 5%. Below the age of 50 the risk is 0.3%.
2. Sex: Men are 35%-40% are at higher risk then women including the fact that men have a higher predilection to rectal cancer then women.
3. Race: Blacks have a 20% higher risk then whites

Risk Factors: Non-Modifiable:

1. Heredity: Family History with first-degree-relative, (parent, child, sibling) has a2-3 times the risk then average. If the relative had colon cancer at a young age that risk increases to 3-6 times. And those patients who had cancer at age 60 yrs or younger have a higher risk of colon cancer in another part of their colon.
2. Lynch Syndrome (Non-Polyposis Colorectal cancer) 2-4% of cases. Lifetime risks of patients with Lynch Syndrome genetic mutation is around 66% in men and 45% in women and the median age is 42 and 47 years respectively.
3. FAP Syndrome due to APC gene has a100% risk by age 45.
4. BRCA1 and BRCA 2 gene mutations also tumor suppressor genes  are associated with a higher risk of colon cancer.
5. Chronic inflammatory diseases of the colon like Crohn’s Disease and Ulcerative Colitis are associated with a higher risk of developing colon cancer.

Risk Factors: Modifiable:

1. Diet: High Red meat content diet is associated with a higher risk. The suspected cause is Heterocyclic Amines (HCAs) that form as a result of high temperature cooking methods. Diets low in fruits and vegetables are also at a higher risk. (Exception=July 4^th)
2. Physical Activity: Sedentary lifestyle is associated with a higher risk, probably due to slower colon-transit-times. (Daily walks)
3. Consumption of Milk and Vitamin D/Calcium reduces the risk of Colon cancer. (A little white moustache)
4. Obesity: A high BMI over 30 especially with abdominal obesity has a higher association with colon cancer risk. (Push away from the table with a little hunger in your stomach)
5. Smoking: Smoking has a higher risk association with rectal cancer in both men and women. (Just say No)
6. Alcohol: Drinking 2-4 drinks a day is associated with a 23% higher risk of developing colon cancer. (Sober up)

Risk Prevention:

1. Aspirin: Daily intake of Aspirin lowers the risk of colon cancer. (An aspirin a day keeps the oncologist away)
2. Anti-inflammatory medications (NSAIDs) also reduce the risk via their inhibition of the COX-2 pathway.
3. Daily Exercise! (Just Do it)

Screening Procedures: (American Cancer Society)

Benefits from Screening:

There is a reduction of incidence of colon cancer by 3% in males and 2.3% females annually. This is significant because it shows the striking impact of screening. All physicians are reminded to encourage their patients aged 50-75 years to undergo screening tests. Given the patients other morbidity issues the appropriate screening test can be entertained and discussed. Soon with the availability of genetic testing in the stool samples the invasive procedures might not be utilized as much for initial screening. Quoting the Imperiale study, “The sensitivity of fecal DNA analysis and FOBT for all cancers and adenomas with high-grade dysplasia was 40.8% versus 14.1%, respectively. Specificity in subjects with negative finding on colonoscopy was 94.4% for fecal DNA and 95.3% for FOBT.”  Even though a joint force recommended the use of DNA testing as a screening tool, the frequency time interval was not established whether it be for every 5-year or 10-year  period. These tests however have to stand the rigors of time and further study based on some questions that have recently been raised.

Unfortunately as the incidence is declining in the age cohort between 50-75 years, it is rising in younger individuals between 20-49 years. This has been ascribed to various reasons including obesity, sedentary lifestyles in the young especially in this digital age and also to the prevalence of HPV.

Stage I

Stage II

Stage III

Stage IV

Stage and Survival:

It must be remembered that since colon cancer formation is a prolonged multistage phenomenon, it is silent through most of its infancy and early growth. Almost two-thirds of the life cycle of the cancer has been lived at the time of diagnosis without screening, therefore early detection is paramount in survival.

Polyp and its removal via Colonoscopy snare

 It is also well known that diagnosing and removing a polyp is tantamount to preventing cancer and thus life-saving by preventing cancer from forming in the first place. It is well established that early stages of any cancer has better prognosis and survival. The 1.1 million survivors with colo-rectal cancer can vouch for the preventative measures.

Colonoscopy

Early screening saves lives, thus preventative colorectal screening is the most compelling argument in medical care! (Cause and Effect)

References:

Role of well-done, grilled red meat, heterocyclic amines (HCAs) in the etiology of human cancer 
Rashmi Sinha, Nathaniel Rothman 
Cancer Letters - 1 September 1999 (Vol. 143, Issue 2, Pages 189-194)


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