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Cancer risks for other sites in addition to breast in CHEK2 c.1100delC families.

PURPOSE: Female CHEK2 c.1100delC heterozygotes are eligible for additional breast surveillance due to an increased breast cancer risk. Increased risks for other cancers have been reported. We studied whether CHEK2 c.1100delC is associated with an increased risk for other cancers within these families.

METHODS: Including 10,780 individuals from 609 families, we calculated standardized incidence rates (SIRs) and absolute excess risk (AER, per 10.000 person years) by comparing first-reported cancer derived from the pedigrees with general Dutch population rates from 1970 onwards. Attained-age analyses were performed for sites in which significant increased risks were found. Considering study design, we primarily focused on cancer risk in women.

RESULTS: We found significant increased risks of colorectal cancer (CRC; SIR=1.43, 95%CI=1.14-1.76; AER=1.43) and hematological cancers (SIR=1.32; 95%CI=1.02-1.67; AER=0.87). CRC was significantly more frequent from age 45 onwards.

CONCLUSION: A significantly increased risk of CRC, and hematological cancers in women was found, starting at a younger age than expected. Currently, colorectal surveillance starts at age 45 in high-risk individuals. Our results suggest that some CHEK2 c.1100delC families might benefit from this surveillance as well, however, further research is needed to determine who may profit from this additional colorectal surveillance.

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