PMID- 15066922
OWN - NLM
STAT- MEDLINE
DCOM- 20050214
LR  - 20191210
IS  - 1055-9965 (Print)
IS  - 1055-9965 (Linking)
VI  - 13
IP  - 4
DP  - 2004 Apr
TI  - A polymorphic locus in the promoter region of the IGFBP3 gene is related to 
      mammographic breast density.
PG  - 573-82
AB  - BACKGROUND: Mammographic breast density is a significant risk factor for breast 
      cancer. Women with dense tissue accounting for more than 60-75% of the area of 
      the breast have a 4- to 6-fold increase in their risk of breast cancer, compared 
      to women with little or no breast density. A high circulating level of 
      insulin-like growth factor-I (IGF-I) and low IGF binding protein 3 (IGFBP-3) 
      level have been associated with increased breast density in premenopausal women. 
      Genetic polymorphisms in the IGF1 and IGFBP3 genes may influence breast and serum 
      levels of these growth factors. The aims of this study were to determine whether 
      polymorphic variations in the IGF1 and IGFBP3 genes are associated with breast 
      density, and serum IGF-I and IGFBP-3 levels, and whether serum IGF-I and IGFBP-3 
      levels are associated with mammographic density. METHODS: A total of 441 white 
      women, recruited from Women's College Hospital (Toronto, Ontario), enrolled in 
      this study. Each woman completed a questionnaire, detailing information on age, 
      menstrual history, hormone use, diet, and medical and mammography history. Blood 
      samples were taken for DNA extraction to genotype the subjects for polymorphic 
      variants in the two candidate genes, and for measurement of circulating levels of 
      IGF-I and IGFBP-3. Mammographic films were retrieved from Women's College 
      Hospital and digitized using a laser film scanner. The digitized images were 
      assessed for breast density using a computer-assisted method. RESULTS: There was 
      a positive association between serum IGFBP-3 levels and the number of A alleles 
      at a previously described polymorphic locus in the promoter region of the IGFBP3 
      gene among premenopausal women (P = 0.01). There was also a positive trend in the 
      mean percentage of breast density by the number of A alleles of the IGFBP3 gene 
      among premenopausal women (P = 0.0005). Women with two A alleles had a 5-fold 
      increase in the odds of having a percentage of breast density greater or equal to 
      28%, compared with women with no A allele (P = 0.002). However, there was no 
      association between serum IGF-I and IGFBP-3 levels and breast density among 
      premenopausal women (P > 0.05). CONCLUSIONS: This is the first study to report a 
      strong relationship between a polymorphic gene locus (IGFBP3) and mammographic 
      breast density. However, we could not confirm an association between serum IGF-I 
      levels and breast density among premenopausal women, as demonstrated in previous 
      studies.
FAU - Lai, Joe H
AU  - Lai JH
AD  - Centre for Research in Women's Health, University of Toronto, 8790 Bay Street, 
      Toronto, Ontario, M5G 1N8 Canada.
FAU - Vesprini, Danny
AU  - Vesprini D
FAU - Zhang, William
AU  - Zhang W
FAU - Yaffe, Martin J
AU  - Yaffe MJ
FAU - Pollak, Michael
AU  - Pollak M
FAU - Narod, Steven A
AU  - Narod SA
LA  - eng
PT  - Evaluation Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer Epidemiol Biomarkers Prev
JT  - Cancer epidemiology, biomarkers & prevention : a publication of the American 
      Association for Cancer Research, cosponsored by the American Society of 
      Preventive Oncology
JID - 9200608
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Insulin-Like Growth Factor Binding Protein 3)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Biomarkers, Tumor/*blood
MH  - Breast Neoplasms/*blood/*diagnostic imaging
MH  - Female
MH  - Humans
MH  - Insulin-Like Growth Factor Binding Protein 3/*blood
MH  - Insulin-Like Growth Factor I/*metabolism
MH  - Mammography
MH  - Middle Aged
MH  - Ontario/epidemiology
MH  - Polymorphism, Genetic
MH  - Predictive Value of Tests
EDAT- 2004/04/07 05:00
MHDA- 2005/02/16 09:00
CRDT- 2004/04/07 05:00
PHST- 2004/04/07 05:00 [pubmed]
PHST- 2005/02/16 09:00 [medline]
PHST- 2004/04/07 05:00 [entrez]
PST - ppublish
SO  - Cancer Epidemiol Biomarkers Prev. 2004 Apr;13(4):573-82.