title: Mutagen sensitivity has high heritability: evidence from a twin study.
abstract: Despite numerous studies showing that mutagen sensitivity is a cancer predisposition factor, the heritability of mutagen sensitivity has not been clearly established. In this report, we used a classic twin study design to examine the role of genetic and environmental factors on the mutagen sensitivity phenotype. Mutagen sensitivity was measured in peripheral blood lymphocytes from 460 individuals [148 pairs of monozygotic (MZ) twins, 57 pairs of dizygotic (DZ) twins, and 50 siblings]. The intraclass correlation coefficients were all significantly higher in MZ twins than in dizygotes (DZ pairs and MZ-sibling pairs combined) for sensitivity to four different mutagen challenges. Applying biometric genetic modeling, we calculated a genetic heritability of 40.7%, 48.0%, 62.5%, and 58.8% for bleomycin, benzo[a]pyrene diol epoxide, gamma-radiation, and 4-nitroquinoline-1-oxide sensitivity, respectively. This study provides the strongest and most direct evidence that mutagen sensitivity is highly heritable, thereby validating the use of mutagen sensitivity as a cancer susceptibility factor.
authors.affiliation: Department of Epidemiology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA. xwu@mdanderson.org
authors.forename: Xifeng
authors.initials: X
authors.lastname: Wu
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Spitz
authors.forename: Christopher I
authors.initials: CI
authors.lastname: Amos
authors.forename: Jie
authors.initials: J
authors.lastname: Lin
authors.forename: Lina
authors.initials: L
authors.lastname: Shao
authors.forename: Jian
authors.initials: J
authors.lastname: Gu
authors.forename: Mariza
authors.initials: M
authors.lastname: de Andrade
authors.forename: Neal L
authors.initials: NL
authors.lastname: Benowitz
authors.forename: Peter G
authors.initials: PG
authors.lastname: Shields
authors.forename: Gary E
authors.initials: GE
authors.lastname: Swan
mesh_terms: D020022:Genetic Predisposition to Disease; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects*; D009152:Mutagenicity Tests; D009153:Mutagens / Q000494:pharmacology*; D009369:Neoplasms / Q000139:chemically induced / Q000235:genetics*; D014427:Twins / Q000097:blood / Q000187:drug effects* / Q000235:genetics
chemical_list: D009153:Mutagens