Towards gene-and gender-based risk estimates in Lynch syndrome; Age-specific incidences for 13 extra-colorectal cancer types

TY - JOUR

T1 - Towards gene-and gender-based risk estimates in Lynch syndrome; Age-specific incidences for 13 extra-colorectal cancer types

AU - Therkildsen, Christina

AU - Ladelund, Steen

AU - Smith-Hansen, Lars

AU - Lindberg, Lars Joachim

AU - Nilbert, Mef

PY - 2017/11/21

Y1 - 2017/11/21

N2 - Background:In Lynch syndrome, inherited mismatch repair (MMR) defects predispose to colorectal cancer and to a wide spectrum of extra-colorectal tumours. Utilising a cohort study design, we aimed to determine the risk of extra-colorectal cancer and to identify yet unrecognised tumour types.Methods:Data from 1624 Lynch syndrome mutation carriers in the Danish hereditary non-polyposis colorectal cancer register were used to estimate the sex-and age-specific incidence rate ratios (IRRs) for 30 extra-colorectal malignancies with comparison to the general population.Results:Significantly increased IRRs were identified for 13 cancer types with differences related to gender, age and disease-predisposing gene. The different cancer types showed variable peak age incidence rates (IRs) with the highest IRs for ovarian cancer at age 30-49 years, for endometrial cancer, breast cancer, renal cell cancer and brain tumours at age 50-69 years, and for urothelial cancer, small bowel cancer, gastric cancer, pancreatic cancer and skin tumours after age 70.Conclusions:The broad spectrum of tumour types that develop at an increased incidence defines Lynch syndrome as a multi-tumour syndrome. The variable incidences in relation to age, gender and gene suggest a need for individualised surveillance.

AB - Background:In Lynch syndrome, inherited mismatch repair (MMR) defects predispose to colorectal cancer and to a wide spectrum of extra-colorectal tumours. Utilising a cohort study design, we aimed to determine the risk of extra-colorectal cancer and to identify yet unrecognised tumour types.Methods:Data from 1624 Lynch syndrome mutation carriers in the Danish hereditary non-polyposis colorectal cancer register were used to estimate the sex-and age-specific incidence rate ratios (IRRs) for 30 extra-colorectal malignancies with comparison to the general population.Results:Significantly increased IRRs were identified for 13 cancer types with differences related to gender, age and disease-predisposing gene. The different cancer types showed variable peak age incidence rates (IRs) with the highest IRs for ovarian cancer at age 30-49 years, for endometrial cancer, breast cancer, renal cell cancer and brain tumours at age 50-69 years, and for urothelial cancer, small bowel cancer, gastric cancer, pancreatic cancer and skin tumours after age 70.Conclusions:The broad spectrum of tumour types that develop at an increased incidence defines Lynch syndrome as a multi-tumour syndrome. The variable incidences in relation to age, gender and gene suggest a need for individualised surveillance.

KW - breast cancer

KW - colorectal cancer

KW - hereditary non-polyposis colorectal cancer

KW - mismatch repair genes

KW - pancreatic cancer

KW - prostate cancer

U2 - 10.1038/bjc.2017.348

DO - 10.1038/bjc.2017.348

M3 - Journal article

C2 - 29065108

AN - SCOPUS:85034841799

SN - 0007-0920

VL - 117

SP - 1702

EP - 1710

JO - British Journal of Cancer

JF - British Journal of Cancer

ER -