A pair of proteins may help explain why people with surgically removed colorectal cancer and who are overweight, physically inactive, and follow a Western-pattern diet may have an increased risk of dying of the disease or other causes, Dana-Farber Cancer Institute scientists report in a new study.

The researchers found that in people who have undergone surgery for colorectal cancer, the levels of two insulin-related proteins in their blood before diagnosis predicted their chances of dying from the cancer or other conditions. Patients with high prediagnosis levels of insulin-like growth factor binding protein-1 (IGFBP-1) were more than half as likely to succumb to the disease; while those with high levels of C-peptide were nearly twice as likely to die. The results are being published online by the Journal of Clinical Oncology on Dec. 8, 2008

The study was the first to consider whether proteins whose blood levels are influenced by lifestyle factors can be a gauge of a patient's chances of surviving stage I-III colorectal cancer. It was designed to explore why people with certain characteristics -- namely, obesity, physical inactivity, and an unhealthy diet -- have an increased risk of colon cancer, cancer recurrence, and death. Such lifestyle factors can lead to high levels of circulating insulin, a hormone that may bind directly to colon cancer cells and spur their growth. High insulin levels also lead to lead to numerous alterations in other blood proteins, which may influence cancer cell growth.

"We don't know yet whether the two proteins identified in this study are part of the actual mechanism that promotes colon cancer recurrence or whether they are simply 'markers' for risk of colon cancer recurrence and death," says the study’s lead author, Brian Wolpin, MD, MPH, of Dana-Farber and Brigham and Women's Hospital (BWH). "But the results underscore the growing evidence that lifestyle choices can have an impact on the risk of recurrence in patients with surgically removed colorectal cancer."

Using data from the Nurses' Health Study and the Health Professionals Follow-up Study -- two long-term studies tracking participants' health -- investigators examined prediagnosis levels of four insulin-related proteins in 373 people who later developed stage I-III colorectal cancer. All four proteins are known to increase or decrease in response to lifestyle factors such as overweight, physical inactivity, and poor nutrition.

Levels of two of the proteins were unrelated to colon cancer recurrence or death. The connection between IGFBP-1, C-peptide, and mortality, however, was strong. Patients with the highest levels of IGFBP-1 had a 56 percent lower risk of death during the study period, and a 57 percent lower risk of dying from colorectal cancer. Researchers speculate that the protein may exert a protective effect by blocking other growth factors that contribute to colon cancer cell proliferation.

High levels of C-peptide, by contrast, doubled the risk of overall death in people with cancer but were not significantly associated with death from colorectal cancer itself. This may be because of an even stronger link between high insulin levels of other potentially fatal diseases such as heart disease and stroke, or because C-peptide is not as accurate a measure of insulin-related hormonal changes as other proteins, the study authors speculate.

Funding for the study was provided by grants from the National Cancer Institute.

The senior author of the paper is Charles Fuchs, MD, MPH, of Dana-Farber and BWH. Co-authors were Jeffrey Meyerhardt, MD, MPH, Kimmie Ng, MD, MPH, Jennifer Chan, MD, MPH, of Dana-Farber and BWH; Andrew Chan, MD, MPH, of Massachusetts General Hospital and BWH; Kana Wu, MD, PhD, of Harvard School of Public Health; Michael Pollak, MD, of the Jewish General Hospital and McGill University in Montreal; and Edward Giovannucci, MD, ScD, of BWH and the Harvard School of Public Health.

About the Dana-Farber Cancer Institute

Dana-Farber Cancer Institute (www.danafarber.org) is a principal teaching affiliate of the Harvard Medical School and is among the leading cancer research and care centers in the United States. It is a founding member of the Dana-Farber/Harvard Cancer Center (DF/HCC), designated a comprehensive cancer center by the National Cancer Institute.

About Colorectal Cancer

Colorectal cancer is also called Colon cancer, and Rectal cancer. Colon cancer is cancer of the large intestine (colon), the lower part of your digestive system. Rectal cancer is cancer of the last 6 inches of the colon. Together, they're often referred to as colorectal cancers.

In the United States, colorectal cancer is the fourth most common cancer in men and women. Caught early, it is often curable.  Not counting skin cancers, colorectal cancer is the third most common cancer found in men and women in this country. The American Cancer Society estimates that there will be about 112,000 new cases of colon cancer and 41,000 new cases of rectal cancer in 2008 in the United States. Combined, they will cause about 49,960 deaths.

• Age: The chances of having colorectal cancer go up after age 50. More than 9 out of 10 people found to have colorectal cancer are older than 50.Having had polyps or colorectal cancer before: Some types of polyps increase the risk of colorectal cancer, especially if they are large or if there are many of them. If you have had colorectal cancer (even if it has been completely removed), you are more likely to have new cancers start in other areas of your colon and rectum. The chances of this happening are greater if you had your first colorectal cancer when you were younger than age 60.
• Having a history of bowel disease: Two bowel diseases, called ulcerative colitis and Crohn's disease, increase the risk of colon cancer. In these diseases, the colon is inflamed over a long period of time. If you have either of these diseases your doctor may want you to have colon screening testing more often. (These diseases are different than irritable bowel syndrome (IBS), which does not carry an increased risk for colorectal cancer.).
• Family history of colorectal cancer: If you have close relatives who have had this cancer, your risk might be increased. This is especially true if the family member got the cancer before age 60. People with a family history of colorectal cancer should talk to their doctors about when and how often to have screening tests.
• Certain family syndromes: A syndrome is a group of symptoms. For example, in some families members tend to get a type of syndrome called FAP that involves having hundreds of polyps in their colon or rectum. Cancer often develops in 1 or more of these polyps.If your doctor tells you that you have a condition that makes you or your family members more likely to get colorectal cancer, you will probably need to begin colon cancer testing at a younger age and you might want to talk about genetic counseling.
• Race or ethnic background: Some racial and ethnic groups such as African Americans and Jews of Eastern European descent (Ashkenazi Jews) have a higher colorectal cancer risk. All of the reasons for this are not yet understood.

• Certain types of diets: A diet that is high in red meats (beef, lamb, or liver) and processed meats such as hot dogs, bologna, and lunch meat can increase your colorectal cancer risk. Cooking meats at very high heat (frying, broiling, or grilling) can create chemicals that might increase cancer risk. Diets high in vegetables and fruits have been linked with a lower risk of colorectal cancer.
• Lack of exercise: Getting more exercise may help reduce your risk.
• Overweight: Being very overweight increases a person's risk of dying from colorectal cancer.
• Smoking: Most people know that smoking causes lung cancer, but long-time smokers are more likely than non-smokers to die of colorectal cancer. Smoking increases the risk of many other cancers, too.
• Alcohol: Heavy use of alcohol has been linked to colorectal cancer.
• Diabetes: People with type 2 diabetes have an increased chance of getting colorectal cancer. They also tend to have a higher death rate from this cancer.

• Other cancers and their treatment: A recent report on testicular cancer survivors found that these men had a higher rate of colorectal cancer. Men who receive radiation therapy for prostate cancer have been reported to have a higher risk of rectal cancer, too.
• Night-shift work: One study suggests that working a night shift at least 3 nights a month for at least 15 years might increase the risk of colorectal cancer in women. More research is needed to check out this finding.

• a change in bowel habits such as diarrhea, constipation, or narrowing of the stool that lasts for more than a few days
• a feeling that you need to have a bowel movement that doesn't go away after doing so
• rectal bleeding, dark stools, or blood in the stool (often, though, the stool will look normal)
• cramping or stomach pain
• weakness and tiredness.

Most people with early colon cancer don't have symptoms, therefore getting tested is very important and can possibly save your life.

About Cancer

Cancer (medical term: malignant neoplasm) is the general name for a group of more than 100 diseases in which a group of cells display uncontrolled growth (division beyond the normal limits), invasion (intrusion on and destruction of adjacent tissues), and sometimes metastasis (spread to other locations in the body via lymph or blood). These three malignant properties of cancers differentiate them from benign tumors, which are self-limited, do not invade or metastasize. Most cancers form a tumor but some, like leukemia, do not. The branch of medicine concerned with the study, diagnosis, treatment, and prevention of cancer is oncology.

Cancer cells can spread to other parts of the body through the blood and lymph systems. Most cancers are named for the organ or type of cell in which they start - for example, cancer that begins in the colon is called colon cancer; cancer that begins in basal cells of the skin is called basal cell carcinoma.

Cancer types can be grouped into broader categories. The main categories of cancer include:

• Carcinoma - a cancer which is derived from the lining cells, or epithelium, of an organ. There are 4 major types of epithelium in the body (Glandular, squamous, transitional, and pseudostratified). Some types are only found in a few select organs such as the lung (pseudostratified) or urinary bladder (transitional).  Carcinomas can arise from any of these epithelial types. For example, breast carcinoma is most commonly derived from the lining cells of the milk producing glands. A carcinoma with a glandular growth pattern is an adenocarcinoma.  Common adenocarcinomas include prostate, colon, and breast.  A carcinoma with a growth pattern resembling the squamous lining cells is termed a squamous cell carcinoma.  Common squamous cell carcinomas are found in the esophagus and skin.  However, any of these organs may have either type of carcinoma arising from it, although these latter diagnoses are exceedingly rare.
• Central nervous system cancers - cancers that begin in the tissues of the brain and spinal cord.
• Leukemia - cancer that starts in blood-forming tissue such as the bone marrow and causes large numbers of abnormal blood cells to be produced and enter the blood.
• Lymphoma - a cancer derived from the white blood cells that are present in the lymphoid tissues of the body.  These sites most commonly include the lymph nodes and spleen. However, lymphomas may arise from any organ and body site.
• Sarcoma - cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue.

Today, millions of people are living with cancer or have had cancer. The risk of developing most types of cancer can be reduced by changes in a person's lifestyle, for example, by quitting smoking, limiting time in the sun, being physically active, and eating a better diet. Half of all men and one-third of all women in the US will develop cancer during their lifetimes.

• Growing Older
• Family history of cancer
• Poor diet, lack of physical activity, or being overweight
• Alcohol