Attenuated familial adenomatous polyposis manifests as autosomal dominant late-onset colorectal cancer

TY - JOUR

T1 - Attenuated familial adenomatous polyposis manifests as autosomal dominant late-onset colorectal cancer

AU - Ibrahim, Abdulla

AU - Barnes, Daniel R.

AU - Dunlop, Jacqueline

AU - Barrowdale, Daniel

AU - Antoniou, Antonis C.

AU - Berg, Jonathan N.

PY - 2014/11

Y1 - 2014/11

N2 - Colorectal cancer (CRC) risk is well defined for families of patients with classical familial adenomatous polyposis (FAP). However, the risk for those with an attenuated form of FAP is less well characterised. In this study, we estimated CRC risks for carriers of a novel germline mutation in the APC gene that causes attenuated FAP (AFAP). We performed genetic testing on 53 individuals from seven AFAP families harbouring an identical APC:c.288T>A mutation. Using a modified segregation analysis, we estimated relative and absolute CRC risks for mutation carriers. Twenty-three individuals harboured the disease causing mutation. CRC occurred in 28 individuals (mean 61.7 years, range 32-80 years). The estimated CRC relative risks for mutation carriers aged 60-69 and ≥70 years were 19 (95% CI: 1.77-204.08) and 45 (95% CI: 11.32-180.10), respectively, while the absolute CRC lifetime risk for men was 94% (95% CI: 67.5-99.9%), and for women, 84% (95% CI: 50.9-99.0%). This study shows that AFAP can manifest as autosomal dominant late-onset CRC. These findings highlight a subgroup of inherited CRCs that require new criteria for identification and surveillance.

AB - Colorectal cancer (CRC) risk is well defined for families of patients with classical familial adenomatous polyposis (FAP). However, the risk for those with an attenuated form of FAP is less well characterised. In this study, we estimated CRC risks for carriers of a novel germline mutation in the APC gene that causes attenuated FAP (AFAP). We performed genetic testing on 53 individuals from seven AFAP families harbouring an identical APC:c.288T>A mutation. Using a modified segregation analysis, we estimated relative and absolute CRC risks for mutation carriers. Twenty-three individuals harboured the disease causing mutation. CRC occurred in 28 individuals (mean 61.7 years, range 32-80 years). The estimated CRC relative risks for mutation carriers aged 60-69 and ≥70 years were 19 (95% CI: 1.77-204.08) and 45 (95% CI: 11.32-180.10), respectively, while the absolute CRC lifetime risk for men was 94% (95% CI: 67.5-99.9%), and for women, 84% (95% CI: 50.9-99.0%). This study shows that AFAP can manifest as autosomal dominant late-onset CRC. These findings highlight a subgroup of inherited CRCs that require new criteria for identification and surveillance.

KW - APC

KW - attenuated FAP

KW - colorectal cancer risk

KW - FAP

KW - segregation analysis

UR - https://www.scopus.com/pages/publications/84908542801

U2 - 10.1038/ejhg.2014.20

DO - 10.1038/ejhg.2014.20

M3 - Article

C2 - 24549056

AN - SCOPUS:84908542801

SN - 1018-4813

VL - 22

SP - 1330

EP - 1333

JO - European Journal of Human Genetics

JF - European Journal of Human Genetics

IS - 11

ER -