TY - JOUR

T1 - Risk of multiple colorectal cancer development depends on age and subgroup in individuals with hereditary predisposition

AU - Lindberg, Lars J.

AU - Wegen-Haitsma, Wia

AU - Ladelund, Steen

AU - Smith-Hansen, Lars

AU - Therkildsen, Christina

AU - Bernstein, Inge

AU - Nilbert, Mef

PY - 2019

Y1 - 2019

N2 - Development of multiple colorectal cancers (CRCs), synchronously or metachronously, is associated with hereditary predisposition for cancer and accurate risk estimates of multiple tumour development are relevant to recommend rational surveillance programs. A cross-sectional study design was used to estimate the risks of synchronous CRC (SCRC) and metachronous CRC (MCRC) based on data from the National Danish Hereditary Nonpolyposis Register. In total, 7100 individuals from families within the subgroups Lynch syndrome, familial CRC (FCC) and moderate risk were used with estimates relative to a non-hereditary population control cohort. SCRC was diagnosed in 7.4% of the Lynch syndrome cases, in 4.2% of FCC cases and 2.5% of the moderate risk cases, which translated to relative risks of 1.9–5.6. The risk of MCRC was distinctively linked to Lynch syndrome with a life-time risk up to 70% and an incidence rate ratio of 5.0. The risk of SCRC was significantly increased in all subgroups of FCC and hereditary CRC, whereas the risk of MCRC was specifically linked to Lynch syndrome. These observations suggest that individuals with FCC or hereditary CRC should be carefully screened for second primary CRC at the time of diagnosis, whereas intensified surveillance for second primary CRC is motivated in Lynch syndrome with lower-intensity programs in families with yet unidentified genetic causes.

AB - Development of multiple colorectal cancers (CRCs), synchronously or metachronously, is associated with hereditary predisposition for cancer and accurate risk estimates of multiple tumour development are relevant to recommend rational surveillance programs. A cross-sectional study design was used to estimate the risks of synchronous CRC (SCRC) and metachronous CRC (MCRC) based on data from the National Danish Hereditary Nonpolyposis Register. In total, 7100 individuals from families within the subgroups Lynch syndrome, familial CRC (FCC) and moderate risk were used with estimates relative to a non-hereditary population control cohort. SCRC was diagnosed in 7.4% of the Lynch syndrome cases, in 4.2% of FCC cases and 2.5% of the moderate risk cases, which translated to relative risks of 1.9–5.6. The risk of MCRC was distinctively linked to Lynch syndrome with a life-time risk up to 70% and an incidence rate ratio of 5.0. The risk of SCRC was significantly increased in all subgroups of FCC and hereditary CRC, whereas the risk of MCRC was specifically linked to Lynch syndrome. These observations suggest that individuals with FCC or hereditary CRC should be carefully screened for second primary CRC at the time of diagnosis, whereas intensified surveillance for second primary CRC is motivated in Lynch syndrome with lower-intensity programs in families with yet unidentified genetic causes.

KW - Colonoscopy

KW - Cross-sectional study

KW - HNPCC

KW - Lynch syndrome

KW - Metachronous neoplasms

KW - Multiple primary neoplasms

KW - Synchronous neoplasms

U2 - 10.1007/s10689-018-0109-z

DO - 10.1007/s10689-018-0109-z

M3 - Journal article

C2 - 30302651

AN - SCOPUS:85054831338

VL - 18

SP - 183

EP - 191

JO - Familial Cancer

JF - Familial Cancer

SN - 1389-9600

IS - 2

ER -