title: Increased Risk for Other Cancers in Addition to Breast Cancer for CHEK2*1100delC Heterozygotes Estimated From the Copenhagen General Population Study.
abstract: OBJECTIVE
  CHEK2 is a cell cycle checkpoint regulator, and the CHEK2*1100delC germline mutation leads to loss of function and increased breast cancer risk. It seems plausible that this mutation could also predispose to other cancers. Therefore, we tested the hypothesis that CHEK2*1100delC heterozygosity is associated with increased risk for other cancers in addition to breast cancer in the general population.
  
  
  METHODS
  We examined 86,975 individuals from the Copenhagen General Population Study, recruited from 2003 through 2010. The participants completed a questionnaire on health and lifestyle, were examined physically, had blood drawn for DNA extraction, were tested for presence of CHEK2*1100delC using Taqman assays and sequencing, and were linked over 1943 through 2011 to the Danish Cancer Registry. Incidences and risks of individual cancer types, including breast cancer, were calculated using Kaplan-Meier estimates, Fine and Gray competing-risks regressions, and stratified analyses with interaction tests.
  
  
  RESULTS
  Among 86,975 individuals, 670 (0.8%) were CHEK2*1100delC heterozygous, 2,442 developed breast cancer, and 6,635 developed other cancers. The age- and sex-adjusted hazard ratio for CHEK2*1100delC heterozygotes compared with noncarriers was 2.08 (95% CI, 1.51 to 2.85) for breast cancer and 1.45 (95% CI, 1.15 to 1.82) for other cancers. When stratifying for sex, the age-adjusted hazard ratios for other cancers were 1.54 (95% CI, 1.08 to 2.18) for women and 1.37 (95% CI, 1.01 to 1.85) for men (sex difference: P = .63). For CHEK2*1100delC heterozygotes compared with noncarriers, the age- and sex-adjusted hazard ratios were 5.76 (95% CI, 2.12 to 15.6) for stomach cancer, 3.61 (95% CI, 1.33 to 9.79) for kidney cancer, 3.45 (95% CI, 1.09 to 10.9) for sarcoma, and 1.60 (95% CI, 1.00 to 2.56) for prostate cancer.
  
  
  CONCLUSIONS
  CHEK2*1100delC heterozygosity is associated with 15% to 82% increased risk for at least some cancers in addition to breast cancer. This information may be useful in clinical counseling of patients with this loss-of-function mutation.
authors.affiliation: All authors: Herlev and Gentofte Hospital, Copenhagen University Hospital, and University of Copenhagen, Denmark.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Näslund-Koch
authors.affiliation: All authors: Herlev and Gentofte Hospital, Copenhagen University Hospital, and University of Copenhagen, Denmark.
authors.forename: Børge G
authors.initials: BG
authors.lastname: Nordestgaard
authors.affiliation: All authors: Herlev and Gentofte Hospital, Copenhagen University Hospital, and University of Copenhagen, Denmark. stig.egil.bojesen@regionh.dk.
authors.forename: Stig E
authors.initials: SE
authors.lastname: Bojesen
mesh_terms: D000368:Aged; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D064447:Checkpoint Kinase 2 / Q000235:genetics*; D003718:Denmark / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009378:Neoplasms, Multiple Primary / Q000453:epidemiology* / Q000235:genetics*; D016017:Odds Ratio; D012042:Registries; D012107:Research Design; D018570:Risk Assessment; D012307:Risk Factors; D011795:Surveys and Questionnaires
chemical_list: D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human