Expanded Extracolonic Tumor Spectrum in MUTYH-Associated Polyposis

Background & Aims

MUTYH-associated polyposis (MAP) is characterized by a lifetime risk of colorectal cancer of up to 100%. However, no systematic evaluation of extracolonic manifestations has been reported.

Methods

A large cohort of MAP patients was recruited from a European multicenter study. Data were collected on 276 cases from 181 unrelated families. Information on extracolonic tumor spectrum and incidence were evaluated to determine cumulative lifetime risk, which was compared with that of the general population to obtain standardized incidence ratios (SIRs).

Results

Duodenal polyposis occurred in 17% of cases; the relative risk (SIR) of duodenal cancer was 129 (95% confidence interval [CI]: 16–466), whereas the lifetime risk was 4%. The incidence of extraintestinal malignancies among cases was almost twice that of the general population (SIR: 1.9; 95% CI: 1.4–2.5), with a lifetime risk of 38%. We observed a significant increase in the incidence of ovarian, bladder, and skin cancers (SIR: 5.7, 7.2, and 2.8, respectively) and a trend of increased risk of breast cancer among cases. The median ages of onset of these 4 malignancies ranged from 51 to 61 years. In contrast to familial adenomatous polyposis, no desmoid tumors were observed, but sebaceous gland tumors, characteristic of the Muir-Torre variant of Lynch syndrome, occurred in 5 patients.

Conclusions

The relative risks for several extraintestinal malignancies increased in patients with MAP, but based on the spectrum of cancers (which overlaps with that of Lynch syndrome) and the relatively advanced age at onset, intensive surveillance measures other than frequent endoscopy are unlikely to be helpful to patients with MAP.

Abbreviations used in this paper: CHRPE, congenital hypertrophy of the retinal pigment epithelium, CI, confidence interval, CRC, colorectal cancer, FAP, familial adenomatous polyposis, MAP, MUTYH-associated polyposis, SGA, sebaceous gland adenomas, SIR, standardized incidence ratios.