title: A strong case for personalized, targeted cancer prevention.
abstract: The study reported by Lee and colleagues in this issue of the journal (beginning on page 185) incorporated global genetic variation within a new assessment of the outcome of a previously reported phase-III trial of low-dose 13-cis-retinoic acid (13-cRA) for preventing second primary tumors (SPT) or the recurrence of head-and-neck cancer. This analysis identified genotypes of common single-nucleotide polymorphisms (SNP) and cumulative effect and potential gene-gene interactions that were highly associated with increased placebo-arm risk (prognostic) and/or with reduced treatment-arm risk and longer event-free survival (predictive). For example, the wild-type rs3118570 SNP of the retinoid X receptor alpha gene (carried by 71% of the 13-cRA trial population) marked a 3.33-fold increased SPT/recurrence risk in the placebo arm and a 38% reduced risk in the treatment arm. Adding two other informative genotypes strengthened the treatment-arm risk reduction to 76%, although the genotype trio reflected only 13% of the trial population. This report extends the concept of personalized therapy to cancer prevention.
authors.affiliation: Cancer Center, Sanford-Burnham Medical Research Institute, La Jolla, CA 92037, USA. mdawson@sanfordburnham.org
authors.forename: Marcia I
authors.initials: MI
authors.lastname: Dawson
mesh_terms: D006258:Head and Neck Neoplasms / Q000235:genetics / Q000517:prevention & control*; D006801:Humans; D015474:Isotretinoin / Q000627:therapeutic use*; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000517:prevention & control*; D016609:Neoplasms, Second Primary / Q000235:genetics / Q000517:prevention & control*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D057285:Precision Medicine; D047490:Retinoid X Receptor alpha / Q000235:genetics; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D047490:Retinoid X Receptor alpha; D015474:Isotretinoin