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Superior survival seen in MUTYH-associated polyposis colorectal cancer
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Five-year survival for patients with MUTYH-associated polyposis colorectal cancer was 15% better than those with non-MUTYH-associated polyposis disease, according to a retrospective, multicenter cohort study.
“In this study, patients with MUTYH-associated polyposis colorectal cancer had statistically significantly better survival than matched control patients,” the researchers concluded. “The reasons for this difference remain unknown, but a compromised base excision repair system could render MUTYH-associated polyposis colorectal cancers more immunogenic than sporadic colorectal cancers, which are characterized predominantly by chromosomal instability. This survival difference may have implications for clinical decision-making in relation to the timing and type of interventions required, such as surgery and chemotherapy.”
The study cohort included 147 patients with MUTYH-associated polyposis disease and 272 matched controls with colorectal cancer. All patients with MUTYH-associated polyposis were biallelic MUTYH mutation carriers and included 113 index patients and 34 of their affected siblings.
All patients in the study were diagnosed from June 1967 to February 2006 in the Netherlands, Germany or the United Kingdom.
Five-year survival was 78% (95% CI, 70-84) for patients with MUTYH-associated polyposis compared with 63% (95% CI, 56-69) for control patients with colorectal cancer from the general population. In comparison, estimated 5-year survival for colorectal cancer is about 54% in Western Europe.
Patients with MUTYH-associated polyposis had more tumors located in the proximal colon, 52% vs. 39%. Patients diagnosed before 1989 were similarly more likely to have more tumors located in the proximal colon, 19% vs. 16%.
After adjusting for age, country, period of diagnosis, stage, sub-site and sex, risk for death for MUTYH-associated polyposis was statistically significantly lower among colorectal cancer patients than among control patients (HR=0.48; 95% CI, 0.32-0.72).
Patients with stage I and II disease had a greater survival benefit (HR=0.45; 95% CI, 0.23-0.91) than patients with stage III and IV disease (HR=0.64; 95% CI, 0.34-1.20), when researchers stratified the data by age.
Patients with MUTYH-associated polyposis colorectal cancer whose tumor was in the colon (HR=0.42; 95% CI, 0.26-0.67) had a similar benefit as patients whose tumor was in the rectum (HR=0.48; 95% CI, 0.22-1.02).
Writing in an accompanying editorial, Henry T. Lynch, MD, and Stephen J. Lanspa, MD, both with the department of preventive medicine and public health at Creighton University in Omaha, Neb., said “recognition of the distinct molecular pathways by which colorectal cancers arise from various genetic mutations, will materially refine our approach to improved surveillance and treatment of patients with hereditary colorectal cancer.
“The ultimate understanding of what drives the development of an individual tumor may enable us to materially improve the care and, in turn, prognosis of cancer patients,” they wrote. “Furthermore, the ultimate understanding of the pathogenetic pathways elicited by these respective mutations may serve as models for studying both survival and increased virulence of hereditary and sporadic colorectal cancers. The genotype and its accompanying cancer phenotype may harbor strong implications for individualizing cancer care.”
For more information:
- Nielsen M. J Natl Cancer Inst.