Department of Preventive Medicine, Keck School of Medicine, University of Southern California, 1441 Eastlake Ave., Norris Cancer Center, Los Angeles, CA 90089, USA.
Cancer Epidemiol Biomarkers Prev. 2012 Apr;21(4):635-44. doi: 10.1158/1055-9965.EPI-11-1042. Epub 2012 Feb 1.
PPARγ is a transcription factor important for adipogenesis and adipocyte differentiation. Data from animal studies suggest that PPARγ may be involved in breast tumorigenesis, but results from epidemiologic studies on the association between PPARγ variation and breast cancer risk have been mixed. Recent data suggest that soy isoflavones can activate PPARγ. We investigated the interrelations of soy, PPARγ, and mammographic density, a biomarker of breast cancer risk in a cross-sectional study of 2,038 women who were members of the population-based Singapore Chinese Health Study Cohort.
We assessed mammographic density using a computer-assisted method. We used linear regression to examine the association between 26 tagging single-nucleotide polymorphisms (SNP) of PPARγ and their interaction with soy intake and mammographic density. To correct for multiple testing, we calculated P values adjusted for multiple correlated tests (P(ACT)).
Out of the 26 tested SNPs in the PPARγ, seven SNPs were individually shown to be statistically significantly associated with mammographic density (P(ACT) = 0.008-0.049). A stepwise regression procedure identified that only rs880663 was independently associated with mammographic density which decreased by 1.89% per-minor allele (P(ACT) = 0.008). This association was significantly stronger in high-soy consumers as mammographic density decreased by 3.97% per-minor allele of rs880663 in high-soy consumers (P(ACT) = 0.006; P for interaction with lower soy intake = 0.017).
Our data support that PPARγ genetic variation may be important in determining mammographic density, particularly in high-soy consumers.
Our findings may help to identify molecular targets and lifestyle intervention for future prevention research.
过氧化物酶体增殖物激活受体γ（PPARγ）是脂肪生成和脂肪细胞分化过程中重要的转录因子。动物研究数据表明，PPARγ 可能与乳腺癌的发生有关，但流行病学研究关于 PPARγ 变异与乳腺癌风险之间的关联结果却存在差异。最近的数据表明，大豆异黄酮可以激活 PPARγ。我们在一项基于人群的新加坡华人健康研究队列的 2038 名女性的横断面研究中，调查了大豆、PPARγ 与乳腺密度（乳腺癌风险的生物标志物）之间的相互关系。
我们使用计算机辅助方法评估乳腺密度。我们使用线性回归来研究 26 个 PPARγ 标签单核苷酸多态性（SNP）与大豆摄入量及其与乳腺密度的相互作用之间的关系。为了校正多重检验，我们计算了校正多重相关检验（P(ACT)）的 P 值。
在 26 个测试的 PPARγ SNP 中，有 7 个 SNP 单独与乳腺密度具有统计学显著相关性（P(ACT) = 0.008-0.049）。逐步回归程序确定只有 rs880663 与乳腺密度独立相关，每一个 minor 等位基因使乳腺密度降低 1.89%（P(ACT) = 0.008）。在高大豆消费者中，这种相关性更强，因为 rs880663 的 minor 等位基因每增加一个，乳腺密度降低 3.97%（在高大豆消费者中 P(ACT) = 0.006；与低大豆摄入的交互作用 P 值 = 0.017）。
我们的数据支持 PPARγ 遗传变异可能在决定乳腺密度方面很重要，尤其是在高大豆消费者中。
我们的研究结果可能有助于确定分子靶标和生活方式干预措施，以用于未来的预防研究。
