This project aims to determine if certain groups of the population will benefit from chemotherapy after removal of colon cancer with intention to cure.

Aim 1
To perform a cohort study to compare the overall survival rates of patients with Dukes' C colorectal cancer who received curative resection surgery treated with or without adjuvant 5-FU-based chemotherapy.

Hypothesis to be tested: Patients with hypermethylated MGMT gene promoter region benefit from adjuvant 5-FU-based chemotherapy and have a lower risk of recurrence of cancer.

Aims 2
To compare the overall survival rates of patients with Dukes' C colorectal cancer treated with curative surgery alone.

Hypothesis to be tested: Is immunohistochemistry (widely available and reliable) an alternative to MSP method of assessing status of MGMT gene in tumour tissue.

Research Plan
The impact of methylation of MGMT gene in survival rate from sporadic CRC will be investigated in a relatively large, population based cohort of patients from the Royal Adelaide Hospital (RAH) who were treated by surgery alone or by surgery and chemotherapy. Minimum data collection for each patient will be sex, age, site of cancer, stage of tumour, microsatellite instability status, methylation of MGMT, immunohistochemistry of MGMT, use of 5-FU-based chemotherapy and overall survival. Molecular analysis for MSI will be carried out using the BAT26 and BAT40 mononucleotide repeat and using PCR-fluorescent technique.

CRC patients will be divided into subgroups according to methylation of MGMT status. Survival rates for 5-FU-treated and non-treated (surgery alone) patients will be compared within each of these groups. Survival analysis will include crude survival, actual survival using the standard Kaplan-Meier procedure and relative survival with the use of computer program.

Potential significance of the overall project
By comparing population-based data on the survival of CRC patients treated with or without standard 5-FU chemotherapy, this project aims to validate results from recent study 1.

Confirmation of these findings would:

1. Question the use of 5-FU chemotheraphy in all Dukes' C stage cancers prompting consideration of giving adjuvant chemotherapy to patients who would benefit from this treatment.
2. Stimulate research into molecular basis of response to 5-FU-based chemotherapy and role of MGMT status on outcome of treatment in colon cancer.