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First pregnancy events and future breast density: modification by age at first pregnancy and specific VEGF and IGF1R gene variants.

Prebil LA, Ereman RR, Powell MJ, Jamshidian F, Kerlikowske K, Shepherd JA, Hurlbert MS, Benz CC - Cancer Causes Control (2014)

Bottom Line: A multivariable regression model including 2,440 parous women showed that PIH during first pregnancy was associated with a statistically significant decrease in %FGV (b = -0.31, 95 % CI -0.52, -0.11), while each month of breast-feeding after first birth was associated with a statistically significant increase in %FGV (b = 0.01, 95% CI 0.003, 0.02).PIH and breast-feeding associations with %FGV were modified by age at first birth.In a subsample of 1,240 women, there was evidence of modification in the association between PIH and %FGV by specific vascular endothelial growth factor (VEGF) (rs3025039) and insulin growth factor receptor-1 (IGFR1) (rs2016347) gene variants.

View Article: PubMed Central - PubMed

Affiliation: Marin County Department of Health and Human Services, 899 Northgate Drive, Suite 415, San Rafael, CA, 94903, USA, lprebil@cal.berkeley.edu.

ABSTRACT

Purpose: Pregnancy characteristics have been associated with breast cancer risk, but information is limited on their relationship with breast density. Our objective was to examine the relationship between first pregnancy characteristics and later life breast density, and whether the association is modified by genotype.

Methods: The Marin Women's Study was initiated to examine breast cancer in a high-incidence mammography population (Marin County, CA). Reproductive characteristics and pregnancy information including pregnancy-induced hypertension (PIH) were self-reported at the time of mammography. Forty-seven candidate single nucleotide polymorphisms were obtained from saliva samples; seven were assessed in relation to PIH and percent fibroglandular volume (%FGV). Breast density assessed as %FGV was measured on full-field digital mammograms by the San Francisco Mammography Registry.

Results: A multivariable regression model including 2,440 parous women showed that PIH during first pregnancy was associated with a statistically significant decrease in %FGV (b = -0.31, 95 % CI -0.52, -0.11), while each month of breast-feeding after first birth was associated with a statistically significant increase in %FGV (b = 0.01, 95% CI 0.003, 0.02). PIH and breast-feeding associations with %FGV were modified by age at first birth. In a subsample of 1,240 women, there was evidence of modification in the association between PIH and %FGV by specific vascular endothelial growth factor (VEGF) (rs3025039) and insulin growth factor receptor-1 (IGFR1) (rs2016347) gene variants.

Conclusion: These findings suggest that first pregnancy characteristics may exert an influence on extent of breast density later in life and that this influence may vary depending on inherited IGFR1 and VEGF genotypes.

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Related in: MedlinePlus

Interaction of PIH and IGFR1
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Related In: Results  -  Collection


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Fig2: Interaction of PIH and IGFR1

Mentions: Multivariable analyses indicated no significant interactions between PIH and five of the seven SNPs tested (Table 4); however, two of the seven SNPs were associated with PIH. A borderline significant interaction was found between the CT genotype of the VEGF SNP and PIH on %FGV (p = 0.063) (compared to the CC genotype). The TT genotype, which has the lowest frequency, did not occur in any of the women with PIH in the first pregnancy and thus does not appear in the results. Statistically significant interactions were found between PIH and the GT genotype of the IGFR1 SNP (p = 0.01) (compared to the GG genotype); those with PIH and the GT genotype had significantly lower %FGV than those with GG genotype of the IGFR1 SNP (joint interaction term p value = 0.03). A borderline significant interaction was found between the TT genotype of the IGFR1 SNP and %FGV (compared to the GG genotype) (p = 0.07). This group was only half the size of the GT group, which may explain why, despite the apparent larger effect seen in the graphic, this did not reach statistical significance. The main effects terms for the GT and TT genotypes of the IGFR1 SNP were both 0.18 in this multivariable model that included the interaction terms. Both of these sets of interactions are presented visually in Figs. 1 and 2, below.Table 4


First pregnancy events and future breast density: modification by age at first pregnancy and specific VEGF and IGF1R gene variants.

Prebil LA, Ereman RR, Powell MJ, Jamshidian F, Kerlikowske K, Shepherd JA, Hurlbert MS, Benz CC - Cancer Causes Control (2014)

Interaction of PIH and IGFR1
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4048469&req=5

Fig2: Interaction of PIH and IGFR1
Mentions: Multivariable analyses indicated no significant interactions between PIH and five of the seven SNPs tested (Table 4); however, two of the seven SNPs were associated with PIH. A borderline significant interaction was found between the CT genotype of the VEGF SNP and PIH on %FGV (p = 0.063) (compared to the CC genotype). The TT genotype, which has the lowest frequency, did not occur in any of the women with PIH in the first pregnancy and thus does not appear in the results. Statistically significant interactions were found between PIH and the GT genotype of the IGFR1 SNP (p = 0.01) (compared to the GG genotype); those with PIH and the GT genotype had significantly lower %FGV than those with GG genotype of the IGFR1 SNP (joint interaction term p value = 0.03). A borderline significant interaction was found between the TT genotype of the IGFR1 SNP and %FGV (compared to the GG genotype) (p = 0.07). This group was only half the size of the GT group, which may explain why, despite the apparent larger effect seen in the graphic, this did not reach statistical significance. The main effects terms for the GT and TT genotypes of the IGFR1 SNP were both 0.18 in this multivariable model that included the interaction terms. Both of these sets of interactions are presented visually in Figs. 1 and 2, below.Table 4

Bottom Line: A multivariable regression model including 2,440 parous women showed that PIH during first pregnancy was associated with a statistically significant decrease in %FGV (b = -0.31, 95 % CI -0.52, -0.11), while each month of breast-feeding after first birth was associated with a statistically significant increase in %FGV (b = 0.01, 95% CI 0.003, 0.02).PIH and breast-feeding associations with %FGV were modified by age at first birth.In a subsample of 1,240 women, there was evidence of modification in the association between PIH and %FGV by specific vascular endothelial growth factor (VEGF) (rs3025039) and insulin growth factor receptor-1 (IGFR1) (rs2016347) gene variants.

View Article: PubMed Central - PubMed

Affiliation: Marin County Department of Health and Human Services, 899 Northgate Drive, Suite 415, San Rafael, CA, 94903, USA, lprebil@cal.berkeley.edu.

ABSTRACT

Purpose: Pregnancy characteristics have been associated with breast cancer risk, but information is limited on their relationship with breast density. Our objective was to examine the relationship between first pregnancy characteristics and later life breast density, and whether the association is modified by genotype.

Methods: The Marin Women's Study was initiated to examine breast cancer in a high-incidence mammography population (Marin County, CA). Reproductive characteristics and pregnancy information including pregnancy-induced hypertension (PIH) were self-reported at the time of mammography. Forty-seven candidate single nucleotide polymorphisms were obtained from saliva samples; seven were assessed in relation to PIH and percent fibroglandular volume (%FGV). Breast density assessed as %FGV was measured on full-field digital mammograms by the San Francisco Mammography Registry.

Results: A multivariable regression model including 2,440 parous women showed that PIH during first pregnancy was associated with a statistically significant decrease in %FGV (b = -0.31, 95 % CI -0.52, -0.11), while each month of breast-feeding after first birth was associated with a statistically significant increase in %FGV (b = 0.01, 95% CI 0.003, 0.02). PIH and breast-feeding associations with %FGV were modified by age at first birth. In a subsample of 1,240 women, there was evidence of modification in the association between PIH and %FGV by specific vascular endothelial growth factor (VEGF) (rs3025039) and insulin growth factor receptor-1 (IGFR1) (rs2016347) gene variants.

Conclusion: These findings suggest that first pregnancy characteristics may exert an influence on extent of breast density later in life and that this influence may vary depending on inherited IGFR1 and VEGF genotypes.

Show MeSH
Related in: MedlinePlus