title: Caution in generalizing known genetic risk markers for breast cancer across all ethnic/racial populations.
abstract: Genome-wide association studies (GWAS) have identified common variants associated with breast cancer risk among women of European and Asian ancestries. To assess the generalizability across ethnic/racial populations of a risk score derived from genotyping 12 highly replicated breast cancer GWAS hits, we performed a case-control study (2224 cases and 2827 controls) nested in the Multiethnic Cohort (MEC) study, which was initiated in 1993-1996 and consists of subjects mainly from European-American, African-American, Native Hawaiian, Japanese and Latino populations. When viewed as a summary risk score, the total number of risk alleles carried by women was significantly associated with breast cancer risk overall (OR per allele, 1.09; 95% CI, 1.06-1.12; P=2.0 × 10(-10)) and in all populations except African-Americans, in which no significant association was observed (OR, 1.03; 95% CI, 0.98-1.08). In aggregate, the number of risk alleles is strongly associated with breast cancer risk in all populations studied except African-Americans. These results emphasize the need for large-scale association studies of multiple racial/ethnic groups for discovery and characterization of risk alleles relevant to all populations in the United States.
authors.affiliation: Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
authors.forename: Fang
authors.initials: F
authors.lastname: Chen
authors.forename: Daniel O
authors.initials: DO
authors.lastname: Stram
authors.forename: Loïc
authors.initials: L
authors.lastname: Le Marchand
authors.forename: Kristine R
authors.initials: KR
authors.lastname: Monroe
authors.forename: Laurence N
authors.initials: LN
authors.lastname: Kolonel
authors.forename: Brian E
authors.initials: BE
authors.lastname: Henderson
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Haiman
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics; D000368:Aged; D000369:Aged, 80 and over; D001213:Asian / Q000235:genetics; D044466:Asian People / Q000235:genetics*; D001943:Breast Neoplasms / Q000208:ethnology* / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D005006:Ethnicity / Q000235:genetics; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D044468:Native Hawaiian or Pacific Islander / Q000235:genetics*; D012306:Risk; D044465:White People / Q000235:genetics*
chemical_list: D005819:Genetic Markers