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

Genet Med. 2024 Sep;26(9):101171. doi: 10.1016/j.gim.2024.101171. Epub 2024 May 31.

Abstract

Purpose: Female CHEK2 c.1100delC heterozygotes are eligible for additional breast surveillance because of 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 onward. Attained-age analyses were performed for sites in which significant increased risks were found. Considering the 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 onward.

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.

Keywords: Breast cancer; CHEK2 c.1100delC; Colorectal cancer; Hematological cancer; Pedigrees.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Breast Neoplasms* / epidemiology
  • Breast Neoplasms* / genetics
  • Checkpoint Kinase 2* / genetics
  • Colorectal Neoplasms* / epidemiology
  • Colorectal Neoplasms* / genetics
  • Female
  • Genetic Predisposition to Disease
  • Hematologic Neoplasms / epidemiology
  • Hematologic Neoplasms / genetics
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Netherlands / epidemiology
  • Pedigree
  • Protein Serine-Threonine Kinases / genetics
  • Risk Factors
  • Young Adult

Substances

  • Checkpoint Kinase 2
  • CHEK2 protein, human
  • Protein Serine-Threonine Kinases