Julius Center for Health Sciences and Primary Care, University Medical Center, Room Str 6.131, PO Box 85500, Utrecht, 3508, GA, The Netherlands.
Breast Cancer Res Treat. 2010 Oct;123(3):843-55. doi: 10.1007/s10549-010-0778-2. Epub 2010 Feb 14.
Mammographic density is strongly related to increased breast cancer risk. Accumulating evidence indicates that a role for the IGF-pathway in mammographic density and breast cancer development. Here, we investigate whether common genetic variation in this pathway influences insulin-like growth factor-I (IGF-I) levels and mammographic density. In 1,916 premenopausal women within the Prospect-EPIC cohort, we examined associations of 14 haplotype tagging SNPs in the ALS, IGFBP1, and IGFBP3 genes with IGF-I circulating levels and mammographic density. In 657 women, who became postmenopausal during follow-up, we investigated how these SNPs were related with the decrease in density over menopause. Linear regression models were used for statistical analysis. None of the ALS or IGFBP3 SNPs were statistically significantly associated with IGF-I levels or mammographic density. The CC genotype for rs1908751 (IGFBP1) was associated with lower levels of IGF-I (110.9 ng/ml) compared to the CT/TT genotypes (115.7 ng/ml) (P = 0.04). Women with the CC genotype also had lower percent density, although not statistically significantly (P = 0.12). Women carrying the AA genotype for rs1995051 (IGFBP1) showed that borderline significantly lower IGF-I levels (P = 0.06) and significantly lower mammographic density (40.3% compared to 43.5% in the GG/GA genotypes; P = 0.05). No relationships were found for any of the SNPs in relation with changes in breast density over menopause. These findings suggest that common genetic variation in the IGFBP1 gene is weakly related to IGF-I levels and mammographic density. Our results do not provide support for such a role of genetic variants in the IGFBP3 and ALS genes.
乳腺密度与乳腺癌风险增加密切相关。越来越多的证据表明，IGF 通路在乳腺密度和乳腺癌发展中起作用。在这里，我们研究了该通路中的常见遗传变异是否会影响胰岛素样生长因子-I（IGF-I）水平和乳腺密度。在前瞻性 EPIC 队列中的 1916 名绝经前妇女中，我们研究了 ALS、IGFBP1 和 IGFBP3 基因中的 14 个单倍型标签 SNP 与 IGF-I 循环水平和乳腺密度的关联。在 657 名随访期间绝经的妇女中，我们研究了这些 SNP 如何与绝经后密度下降相关。线性回归模型用于统计分析。ALS 或 IGFBP3 中的任何 SNP 与 IGF-I 水平或乳腺密度均无统计学显著关联。rs1908751（IGFBP1）的 CC 基因型与 CT/TT 基因型相比，IGF-I 水平较低（110.9ng/ml）（P=0.04）。CC 基因型的女性乳腺密度也较低，尽管无统计学意义（P=0.12）。rs1995051（IGFBP1）的 AA 基因型的女性 IGF-I 水平略低（P=0.06），乳腺密度也明显较低（40.3%比 GG/GA 基因型的 43.5%；P=0.05）。在与绝经后乳腺密度变化相关的任何 SNP 中均未发现关系。这些发现表明，IGFBP1 基因中的常见遗传变异与 IGF-I 水平和乳腺密度弱相关。我们的结果不支持 IGFBP3 和 ALS 基因中的遗传变异在这方面起作用。
