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.
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.
Authors: Fredrick R Schumacher; Iona Cheng; Matthew L Freedman; Lorelei Mucci; Naomi E Allen; Michael N Pollak; Richard B Hayes; Daniel O Stram; Federico Canzian; Brian E Henderson; David J Hunter; Jarmo Virtamo; Jonas Manjer; J Michael Gaziano; Laurence N Kolonel; Anne Tjønneland; Demetrius Albanes; Eugenia E Calle; Edward Giovannucci; E David Crawford; Christopher A Haiman; Peter Kraft; Walter C Willett; Michael J Thun; Loïc Le Marchand; Rudolf Kaaks; Heather Spencer Feigelson; H Bas Bueno-de-Mesquita; Domenico Palli; Elio Riboli; Eiliv Lund; Pilar Amiano; Gerald Andriole; Alison M Dunning; Dimitrios Trichopoulos; Meir J Stampfer; Timothy J Key; Jing Ma Journal: Hum Mol Genet Date: 2010-05-19 Impact factor: 6.150
Authors: Fangyi Gu; Fredrick R Schumacher; Federico Canzian; Naomi E Allen; Demetrius Albanes; Christine D Berg; Sonja I Berndt; Heiner Boeing; H Bas Bueno-de-Mesquita; Julie E Buring; Nathalie Chabbert-Buffet; Stephen J Chanock; Françoise Clavel-Chapelon; Vanessa Dumeaux; J Michael Gaziano; Edward L Giovannucci; Christopher A Haiman; Susan E Hankinson; Richard B Hayes; Brian E Henderson; David J Hunter; Robert N Hoover; Mattias Johansson; Timothy J Key; Kay-Tee Khaw; Laurence N Kolonel; Pagona Lagiou; I-Min Lee; Loic LeMarchand; Eiliv Lund; Jing Ma; N Charlotte Onland-Moret; Kim Overvad; Laudina Rodriguez; Carlotta Sacerdote; Maria-José Sánchez; Meir J Stampfer; Pär Stattin; Daniel O Stram; Gilles Thomas; Michael J Thun; Anne Tjønneland; Dimitrios Trichopoulos; Rosario Tumino; Jarmo Virtamo; Stephanie J Weinstein; Walter C Willett; Meredith Yeager; Shumin M Zhang; Rudolf Kaaks; Elio Riboli; Regina G Ziegler; Peter Kraft Journal: Cancer Epidemiol Biomarkers Prev Date: 2010-09-01 Impact factor: 4.254
Authors: Cathrine Hoyo; Janet Grubber; Wendy Demark-Wahnefried; Jeffrey R Marks; Stephen J Freedland; Amy S Jeffreys; Steven C Grambow; Robert M Wenham; Philip J Walther; Joellen M Schildkraut Journal: J Natl Med Assoc Date: 2007-07 Impact factor: 1.798
Authors: Aimee A D'Aloisio; Jane C Schroeder; Kari E North; Charles Poole; Suzanne L West; Gregory S Travlos; Donna D Baird Journal: Cancer Epidemiol Biomarkers Prev Date: 2009-02-24 Impact factor: 4.254
Authors: Celia M T Greenwood; Andrew D Paterson; Linda Linton; Irene L Andrulis; Carmel Apicella; Apostolos Dimitromanolakis; Valentina Kriukov; Lisa J Martin; Ayesha Salleh; Elena Samiltchuk; Rashmi V Parekh; Melissa C Southey; Esther M John; John L Hopper; Norman F Boyd; Johanna M Rommens Journal: Breast Cancer Res Date: 2011-12-21 Impact factor: 6.466
Authors: Rulla M Tamimi; David Cox; Peter Kraft; Graham A Colditz; Susan E Hankinson; David J Hunter Journal: Breast Cancer Res Date: 2008-08-05 Impact factor: 6.466