Abstract and Introduction
Abstract
Background MUTYH-associated polyposis is a recessively inherited disorder characterized by a lifetime risk of colorectal cancer that is up to 100%. Because specific histological and molecular genetic features of MUTYH-associated polyposis colorectal cancers might influence tumor behavior and patient survival, we compared survival between patients with MUTYH-associated polyposis colorectal cancer and matched control patients with colorectal cancer from the general population.
Methods In this retrospective multicenter cohort study from Europe, 147 patients with MUTYH-associated polyposis colorectal cancer were compared with 272 population-based control patients with colorectal cancer who were matched for country, age at diagnosis, year of diagnosis, stage, and subsite of colorectal cancer. Kaplan–Meier survival and Cox regression analyses were used to compare survival between patients with MUTYH-associated polyposis colorectal cancer and control patients with colorectal cancer. All statistical tests were two-sided.
Results Five-year survival for patients with MUTYH-associated polyposis colorectal cancer was 78% (95% confidence interval [CI] = 70% to 84%) and for control patients was 63% (95% CI = 56% to 69%) (log-rank test, P = .002). After adjustment for differences in age, stage, sex, subsite, country, and year of diagnosis, survival remained better for MUTYH-associated polyposis colorectal cancer patients than for control patients (hazard ratio of death = 0.48, 95% CI = 0.32 to 0.72).
Conclusions In a European study cohort, we found statistically significantly better survival for patients with MUTYH-associated polyposis colorectal cancer than for matched control patients with colorectal cancer.
Introduction
Worldwide, colorectal cancer accounted for about one million newly diagnosed cancers in 2002, representing approximately 10% of all new cancers. Estimated 5-year survival for colorectal cancer is approximately 54% in Western Europe. Tumors in patients with inherited cancer syndromes may arise through distinct molecular genetic pathways and show histological features that are different from those in most sporadic tumors. These differences might, at least in part, influence tumor behavior and patient survival. For instance, mismatch repair–deficient tumors (associated with Lynch syndrome or sporadic microsatellite instability) have been reported to have a decreased likelihood of metastasizing, and patients with such tumors have better survival than patients with sporadic colorectal cancer, although some reports have not confirmed this finding.
In 2002, the first autosomal recessive inherited form of colorectal cancer, MUTYH-associated polyposis (Mendelian Inheritance in Man #608456), was described.MUTYH-associated polyposis is believed to be responsible for 0.3%–1% of all colorectal cancers.
The MUTYH protein is a base excision repair glycosylase that is involved in the repair of DNA damage resulting from the oxidation of guanine nucleotides. The oxidation product of guanine, 8-oxo-7,8-dihydro-2′-deoxyguanosine can mispair with adenine, leading to a transversion in which a G:C base pair is replaced with a T:A base pair. The MUTYH protein prevents these transversions by scanning the newly synthesized DNA strand for any mispaired adenines, with guanines or 8-oxo-7,8-dihydro-2′-deoxyguanosines, and excising them.
The risk of colorectal cancer in individuals with biallelic MUTYH mutations is high. The penetrance of colorectal cancer in patients with MUTYH-associated polyposis at age 60 years was estimated to be 100% in one study and 43% in another.
We hypothesized that survival of patients with MUTYH-associated polyposis and colorectal cancer might differ from that of colorectal cancer patients from the general population because of the distinct mutational mechanism underlying MUTYH-associated polyposis. The purpose of this study was to compare survival between patients with MUTYH-associated polyposis colorectal cancer and matched control patients with colorectal cancer from the general population.