Colorectal

Cancer in the colon/rectum constitutes 15% of all cancer cases in Norway. Next after breast cancer in women and prostate cancer in men, cancer of the colon/rectum is the most common cancer form for each sex. Rectal cancer constitutes 5% for each sex, while colon cancer constitutes 9% in men and 12% in women.

Overview

Colorectal cancer was the second most common cancer in Norwegian men and women in 2005. Colorectal cancer is one of the most frequent causes of cancer death in the Norwegian population after lung cancer and prostate cancer.

The Cancer Registry of Norway shows a five year relative survival probability of 56.3% in colon cancer for men and 58.5% for women, diagnosed 1996-2000. In cancers of the rectum, rectosigmoideum and anus the survival probability for the same cohort shows 58.2% and 60.3 % for men and women respectively. The age-standardized incidence of colorectal cancer varies around the world, with up to 20-fold differences in the western world and developing countries.

Background

Colorectal Cancer Basic Overview

In Norway, the occurence of cancer in the colon and rectum is higher than in any other european country and the USA. The cancer occurs seldomly before the age of 30, and is most common in the ages between 60 and 70. The occurrence of both colon and rectum cancer has increased 130 % in the past 40 years for both sexes. The occurrence varies strongly between industrialized and developing countries. Changes over time and geographic variations indicate that environment poses a risk factor.

The expected survival rates have steadily improved in the past 30 years. There is an 80 % chance of survival after five years for patients who are operated for localized disease. Around 60 % survival after five years for patients with spreading to the lymph nodes. Around 5 % survival after five years for patients with distant spreading.

Cancer in the colon and rectum is usually considered one cancer type. There are however genetic evidence which show that right and left side colon cancers and rectum cancers can have different pathogeneses, and appear to have different responses to treatment.

About 98 % of all malignant tumors in the colon/rectum are adenocarcinomas. The rest are spinocellular carcinomas, carcinoids, lymphomas, and sarcomas. The tumors are most often localized to the ascending colon, sigmoid colon and rectum, rarely in the middle part of the colon.

There is not enough evidence to prove the benefit of screening for colorectal cancer, to implement this practice in Norway. A Norwegian study is underway.

Treatment today is primarily determined by the tumor stage at diagnosis (cTNM). Surgery is the most effective treatment and is performed on all patients if there are no contraindications present. Surgery is performed to gain control of the primary tumor and sometimes as a palliative measure. The clinical behaviour of the tumor can however vary a lot, even within the same TNM group. This makes it difficult to predict the patient’s response to treatment and clinical course. Today there is a need for more better methods of classifying colorectal tumors, as well as a strong need for good prognostic markers to better predict the course of the disease.

Scientific Approach

The present routine staging and preferred treatment is based on TNM staging or Dukes classification, but is still not satisfying in predicting individual clinical outcome in patients. We search for complimentary prognostic markers to easier subclassify established prognostic groups and to predict a more certain individual clinical outcome.

Ongoing Studies

We are currently working on three main projects on colorectal cancer, all in cooperation with other Norwegian hospitals. On all projects we are investigating large scale genomic instability as a possible prognostic marker, using Nucleotyping. We are also making TMA and experimental databases for studying immunohistochemistry on colorectal specimens.

Molecular Classification of Colorectal Cancer

The largest project is in collaboration with Aker University Hospital (AUS), Division of Gastrointestinal Surgery. A total of 1000 patients operated on for sporadic colon and rectum cancer since 1993 have been followed up at Aker.

Nucleotyping in Sporadic Colon Cancer

We also have two collaborations with Akershus University Hospital (AHUS). Sporadic colon cancer on 200 patients is a collaboration with Division of Surgery, and Inflammatory Bowel Disease.

Nucleotyping in IBD Related Cancer

Related Colorectal cancer on 60 patients is a collaboration with Division of Medicine.

Research Materials

Our studies of cancer in the colon/rectum now consist of about 1350 patients and all of these are treated at other hospitals (AUS and AHUS). Our studies are only a portion of larger studies, but here only our own activity is described. The study is based on the following three series:

• M51 – Molecular classification of colorectal cancer. The material consists of all patients operated on for cancer of the colon or rectum at Aker University Hospital (AUS) since 1993, and now consists of operative specimens from about 1000 patients. In addition to the tumor material, we have clinical and histopathological data as well as consistent postoperative follow-up. Wide molecular classification is performed as well as tumor tests at the Centre for Cancer Biomedicine. Our contribution is DNA ploidy and Nucleotyping, as well as production of TMA blocks.?
• M34 – Sporadic colon cancer.The material consists of tumors from tests from 219 patients with cancer of the colon, which have been operated on with a curative goal at Akershus University Hospital (AHUS) in the time from 1988-2000. Clinical and histopathological data is present, and patients are followed up for an average of 5,6 years.
• M33 – IBD related colon cancer. The study is a collaboration with AHUS. The material is from a group of patients with the diagnosis Inflammatory Bowel Disease (IBD) which later developed into colon cancer. The patients were followed up with biopsies for several years until diagnosis of cancer. At the end of 2007, we had recieved 201 blocks from 63 patients, divided by 61 cancers and 140 biopsies from outside the tumor. The goal of the study is to see if Nucleotyping and/or DNA ploidy can identify patients who develop colon cancer before the disease has clinically manifested. In the first round, we have acctepted material from cancer tests to examine whether DNA ploidy has a prognostic value after an operation. After analysis of phase 1, it will be determined whether phase 2 (pre-cancer IBD tests) will be started.

Publications

Lothe RA, Fossli T, Danielsen HE, Stenwig AE, Nesland JM, Gallie B, Børresen
Molecular genetic studies of tumor suppressor gene regions on chromosomes 13 and 17 in colorectal tumors
AL. J Natl Cancer Inst. 1992 Jul 15;84(14):1100-8.

Media

Colorectal Cancer Basic Overview
Detail of colorectal cancer. Curtsy of The National Cancer Institute
Colorectal Zones
Colorectal Incision points
Colorectal nerves
Colorectal regions

Contact Information

If you have questions regarding the project, please contact us for more information.

Responsible clinicians
Arild Nesbakken
Johan Bondi
Stephen Brackmann

Head of Section for Interphase Genetics
Maria E.Pretorius

Collaborators
Ragnhild Lothe (RR)
Arild Nesbakken (AUS)
Johan Bondi (AHUS)
Ida Bukholm (AHUS)
Stephan Brackmann (AHUS)
Marianne Merok (AHUS)
Bjørn Risberg (RR)
Centre for Cancer Biomedicine