title: Familial Risk and Heritability of Colorectal Cancer in the Nordic Twin Study of Cancer.
abstract: OBJECTIVE
  We analyzed data from twins to determine how much the familial risk of colorectal cancer can be attributed to genetic factors vs environment. We also examined whether heritability is distinct for colon vs rectal cancer, given evidence of distinct etiologies.
  
  
  METHODS
  Our data set included 39,990 monozygotic and 61,443 same-sex dizygotic twins from the Nordic Twin Study of Cancer. We compared each cancer's risk in twins of affected co-twins relative to the cohort risk (familial risk ratio [FRR]). We then estimated the proportion of variation in risk that could be attributed to genetic factors (heritability).
  
  
  RESULTS
  From earliest registration in 1943 through 2010, there were 1861 individuals diagnosed with colon cancer and 1268 diagnosed with rectal cancer. Monozygotic twins of affected co-twins had an FRR for colorectal cancer of 3.1 (95% confidence interval [CI], 2.4-3.8) relative to the cohort risk. Dizygotic twins of affected co-twins had an FRR for colorectal cancer of 2.2 (95% CI, 1.7-2.7). We estimated that 40% (95% CI, 33%-48%) of the variation in colorectal cancer risk could be attributed to genetic factors; unique environment only accounted for the remaining liability. For colon cancer, the FRR was 3.3 (95% CI, 2.1-4.5) for monozygotic twins and 2.6 (95% CI, 1.7-3.5) for dizygotic twins. For rectal cancer, comparable estimates were 3.3 (95% CI, 1.5-5.1) for monozygotic twins and 2.6 (95% CI, 1.2-4.0) for dizygotic twins. Heritability estimates for colon and rectal cancer were 16% (95% CI, 0-46%) and 15% (95% CI, 0-50%), common environment estimates were 15% (95% CI, 0-38%) and 11% (95% CI, 0-38%), and unique environment estimates were 68% (95% CI, 57%-79%) and 75% (95% CI, 61%-88%), respectively.
  
  
  CONCLUSIONS
  Interindividual genetic differences could account for 40% of the variation in susceptibility to colorectal cancer; risk for colon and rectal cancers might have less of a genetic component than risk for colorectal cancer. Siblings, and particularly monozygotic co-twins, of individuals with colon or rectal cancer should consider personalized screening.
authors.affiliation: Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts; Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California. Electronic address: Rebecca.Graff@ucsf.edu.
authors.forename: Rebecca E
authors.initials: RE
authors.lastname: Graff
authors.affiliation: Epidemiology, Biostatistics and Biodemography, Department of Public Health, University of Southern Denmark, Denmark; The Danish Twin Registry, University of Southern Denmark, Denmark.
authors.forename: Sören
authors.initials: S
authors.lastname: Möller
authors.affiliation: Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California.
authors.forename: Michael N
authors.initials: MN
authors.lastname: Passarelli
authors.affiliation: Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California; Institute for Human Genetics, University of California San Francisco, San Francisco, California; Department of Urology, University of California San Francisco, San Francisco, California; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California.
authors.forename: John S
authors.initials: JS
authors.lastname: Witte
authors.affiliation: Epidemiology, Biostatistics and Biodemography, Department of Public Health, University of Southern Denmark, Denmark; The Danish Twin Registry, University of Southern Denmark, Denmark.
authors.forename: Axel
authors.initials: A
authors.lastname: Skytthe
authors.affiliation: Epidemiology, Biostatistics and Biodemography, Department of Public Health, University of Southern Denmark, Denmark; The Danish Twin Registry, University of Southern Denmark, Denmark.
authors.forename: Kaare
authors.initials: K
authors.lastname: Christensen
authors.affiliation: Epidemiology, Biostatistics and Biodemography, Department of Public Health, University of Southern Denmark, Denmark; The Danish Twin Registry, University of Southern Denmark, Denmark.
authors.forename: Qihua
authors.initials: Q
authors.lastname: Tan
authors.affiliation: Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Hans-Olov
authors.initials: HO
authors.lastname: Adami
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Kamila
authors.initials: K
authors.lastname: Czene
authors.affiliation: Department of Genetics and Bioinformatics, Norwegian Institute of Public Health, Oslo, Norway.
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Harris
authors.affiliation: Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer Research, Helsinki, Finland; School of Health Sciences, University of Tampere, Tampere, Finland.
authors.forename: Eero
authors.initials: E
authors.lastname: Pukkala
authors.affiliation: Department of Public Health, University of Helsinki, Helsinki, Finland; National Institute for Health and Welfare, Department of Health, Helsinki, Finland; Institute for Molecular Medicine Finland, Helsinki, Finland.
authors.forename: Jaakko
authors.initials: J
authors.lastname: Kaprio
authors.affiliation: Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts; Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Edward L
authors.initials: EL
authors.lastname: Giovannucci
authors.affiliation: Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts; Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; Centre for Public Health Sciences, University of Iceland, Reykjavik, Iceland.
authors.forename: Lorelei A
authors.initials: LA
authors.lastname: Mucci
authors.affiliation: Epidemiology, Biostatistics and Biodemography, Department of Public Health, University of Southern Denmark, Denmark; The Danish Twin Registry, University of Southern Denmark, Denmark.
authors.forename: Jacob B
authors.initials: JB
authors.lastname: Hjelmborg
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D003110:Colonic Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D005060:Europe / Q000453:epidemiology; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007206:Individuality; D007223:Infant; D008297:Male; D008875:Middle Aged; D012004:Rectal Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D018570:Risk Assessment; D014429:Twins, Dizygotic; D014430:Twins, Monozygotic; D055815:Young Adult
keywords: Biometric Modeling; Concordance Relative Risk; Genetic Susceptibility; Zygosity