Colon cancer patients with a family history of colorectal cancer have lower risk of recurrence and death

Patients with stage III colon cancer who have a family history of colorectal cancer in a first-degree relative have a lower risk of recurrence and death than those without, according to a major study looking at the link between inherited colorectal cancer and survival.

Between one in every six and one in every five people (16%-20%) with colorectal cancer has a first-degree relative – a parent or sibling – with colorectal cancer. Studies have shown that a history of colorectal cancer in a first-degree relative nearly doubles the risk of developing the disease. However, the influence of family history on cancer recurrence and survival has previously been unclear.

The study followed up 1087 patients with stage III colon cancer – spread from the colon to the lymph glands but not elsewhere - who were taking part in a clinical trial of chemotherapy. Rates of recurrence and death were compared over a median follow-up of 5.6 years in the 195 patients (17.9%) with a family history of colorectal cancer in a first-degree relative with the 892 patients without a close relative with the disease.

Results showed that cancer recurrence or death occurred in 29% of the patients with a family history of colorectal cancer, compared to 38% of those without a first-degree relative with the condition. The risk of recurrence was 26% lower in patients with a family history of colorectal cancer (hazard ratio [HR] 0.74; 95% confidence interval [CI] 0.55-0.99), while their risk of death was 25% lower (HR 0.75; 95% CI 0.54-1.05).
The reduction in risk of cancer recurrence or death associated with a family history became stronger as the number of affected first-degree relatives increased. Compared to those without a family history, patients with one affected relative had a 23% greater disease-free survival (HR 0.77; 95% CI 0.57-1.04), increasing to a 51% (HR 0.49; 95% CI 0.23-1.04) in those with two or more affected relatives (p=0.01 for trend with increasing number of relatives). The improved disease-free survival associated with a family history of colorectal cancer was independent of measures of gene damage – microsatellite instability and mismatch repair proteins MLH1 and MSH2 – commonly found in inherited colorectal tumours.

The study authors, led by Jennifer Chan, from the Dana-Farber Cancer Institute, Boston , USA , said: “Among patients with stage III colon cancer receiving adjuvant chemotherapy, a family history of colorectal cancer is associated with a significant reduction in cancer recurrence and death.” They added: “This finding may reflect a distinct underlying molecular and pathogenic mechanism in cancers that develop in the setting of a common family history.” More research is needed to elucidate the potential mechanisms by which a common family history may influence outcomes for patients with colorectal cancer, they concluded.

In an editorial accompanying the study report, Boris Pasche, from Northwestern University Feinberg School of Medicine, Chicago , USA , noted that analyses of molecular predictors of survival after adjuvant chemotherapy for colon cancer have shown that loss of chromosome 18 correlates with a poor prognosis. He suggested that the next obvious step would be to determine whether loss of chromosome 18 is less common in the tumours from patients with a family history of colorectal cancer. “If these intriguing findings are validated in other studies, family history may well become a new prognostic factor in colorectal cancer,” he said.

Should this be the case, genome-wide association studies and tumour gene expression profiling studies will be warranted to identify genetic features associated with a family history of colorectal cancer and favourable outcome following adjuvant chemotherapy, Dr Pasche suggested. “The study by Chan et al suggests that family history of colorectal cancer will lead to the identification of novel genetic features predictive of response to chemotherapy. Familial colorectal cancer may therefore confirm its role as a genetics treasure trove for medical discovery.”