Genetic determinants of circulating insulin-like growth factor (IGF)-I, IGF binding protein (BP)-1, and IGFBP-3 levels in a multiethnic population.
BACKGROUND
Both circulating levels and genetic variation of IGFs have been associated with cancer risk, yet the relationship between the two is not well understood.


OBJECTIVE
To investigate whether common genetic variation in IGF1, IGF binding protein 1 (IGFBP1), and IGFBP3 influences circulating levels of IGF-I, IGFBP-1, and IGFBP-3, we conducted a cross-sectional study of African-American, Native Hawaiian, Japanese-American, Latino, and white men and women in the Multiethnic Cohort.


METHODS
Plasma levels of IGF-I, IGFBP-1, and IGBFP-3 were measured by ELISA in a random sample of 837 Multiethnic Cohort participants. Previously identified tag single nucleotide polymorphisms (SNPs) for IGF1 (29 tag SNPs) and IGFBP1/IGFBP3 (23 tag SNPs) were genotyped among the 837 participants. Analysis of covariance was conducted to test for differences in mean IGF-I, IGFBP-1, and IGFBP-3 levels across respective IGF1, IGFBP1, and IGFBP3 genotypes, adjusting for previously identified dietary and lifestyle correlates.


RESULTS
Five highly correlated IGFBP3 SNPs (rs3110697, rs2854747, rs2854746, rs2854744, and rs2132570) demonstrated strongly significant associations with IGFBP-3 levels when conservatively adjusted for multiple hypothesis testing (Bonferroni adjusted P trends = 7.75 x 10(-8) to 1.44 x 10(-5)). Patterns of associations were consistent across the five racial/ethnic groups.


CONCLUSIONS
In summary, our study suggests that common genetic variation in IGFBP3 influences circulating levels of IGFBP-3 among African-Americans, Native Hawaiians, Japanese-Americans, Latinos, and whites.
Cheng
Iona
I
Department of Epidemiology and Biostatistics, University of California, San Francisco, California 94143-0794, USA. chengi@humgen.ucsf.edu
DeLellis Henderson
Katherine
K
Haiman
Christopher A
CA
Kolonel
Laurence N
LN
Henderson
Brian E
BE
Freedman
Matthew L
ML
Le Marchand
Loïc
L
D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood* / Q000235:genetics*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood* / Q000235:genetics*; D007334:Insulin-Like Growth Factor I / Q000032:analysis* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
D018970:Insulin-Like Growth Factor Binding Protein 1; D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I