Department of Preventive Medicine, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, California, United States of America.
PLoS One. 2013 Jun 7;8(6):e65313. doi: 10.1371/journal.pone.0065313. Print 2013.
Mammographic density (MD) has been found to be an independent risk factor for breast cancer. Although data from twin studies suggest that MD has a strong genetic component, the exact genes involved remain to be identified. Alterations in stromal composition and the number of epithelial cells are the most predominant histopathological determinants of mammographic density. Interactions between the breast stroma and epithelium are critically important in the maturation and development of the mammary gland and the cross-talk between these cells are mediated by paracrine growth factors and cytokines. The potential impact of genetic variation in growth factors and cytokines on MD is largely unknown.
We investigated the association between 89 single nucleotide polymorphisms (SNPs) in 7 cytokine/growth-factor genes (FGFR2, IGFBP1, IGFBP3, TGFB1, TNF, VEGF, IL6) and percent MD in 301 premenopausal women (aged 50 to 55 years) participating in the Norwegian Breast Cancer Screening Program. We evaluated the suggestive associations in 216 premenopausal Singapore Chinese Women of the same age.
We found statistically significant associations between 9 tagging SNPs in the IL6 gene and MD in Norwegian women; the effect ranged from 3-5% in MD per variant allele (p-values = 0.02 to 0.0002). One SNP in the IL6 (rs10242595) significantly influenced MD in Singapore Chinese women.
Genetic variations in IL6 may be associated with MD and therefore may be an indicator of breast cancer risk in premenopausal women.
乳腺密度（MD）已被发现是乳腺癌的一个独立危险因素。尽管来自双胞胎研究的数据表明 MD 具有很强的遗传成分，但涉及的确切基因仍有待确定。基质成分和上皮细胞数量的改变是乳腺密度的最主要组织病理学决定因素。乳腺基质和上皮细胞之间的相互作用对于乳腺的成熟和发育至关重要，这些细胞之间的串扰是通过旁分泌生长因子和细胞因子介导的。遗传变异对生长因子和细胞因子对 MD 的潜在影响在很大程度上是未知的。
我们研究了 7 个细胞因子/生长因子基因（FGFR2、IGFBP1、IGFBP3、TGFB1、TNF、VEGF、IL6）中的 89 个单核苷酸多态性（SNP）与 301 名参加挪威乳腺癌筛查计划的 50 至 55 岁的绝经前妇女的 MD 之间的关联。我们评估了相同年龄的 216 名新加坡华裔绝经前妇女中这些关联的提示性作用。
我们发现，挪威女性的 IL6 基因中的 9 个标记 SNP 与 MD 之间存在统计学上显著的关联；每个变体等位基因的 MD 变化范围为 3-5%（p 值为 0.02 至 0.0002）。IL6 中的一个 SNP（rs10242595）显著影响了新加坡华裔妇女的 MD。
IL6 中的遗传变异可能与 MD 相关，因此可能是绝经前妇女乳腺癌风险的一个指标。
