Stone Jennifer, Gurrin Lyle C, Byrnes Graham B, Schroen Christopher J, Treloar Susan A, Padilla Emma J D, Dite Gillian S, Southey Melissa C, Hayes Vanessa M, Hopper John L
Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, University of Melbourne, 2/723 Swanston Street, Carlton, Victoria 3053, Australia.
Cancer Epidemiol Biomarkers Prev. 2007 Jul;16(7):1479-84. doi: 10.1158/1055-9965.EPI-07-0107.
Mammographic density, the light/white radiographic appearance on a mammogram that represents connective and epithelial tissue, is a strong risk factor for breast cancer which seems to be highly heritable. Little is known about its genetic determinants.
We studied 457 women from 207 sisterhoods (104 monozygotic twins, 182 dizygotic twins, and 171 singletons). Percentage mammographic density (PMD) as well as dense area and nondense area were calculated using a computer-assisted method. We measured six single nucleotide polymorphisms from six candidate genes (COMT, HSD3B1, IGFBP3, HER2, XPD, and XRCC3). Associations between genotypes and mammographic measures were tested (a) cross-sectionally using a multivariate normal model fitted using FISHER that allowed separate correlations for monozygotic, dizygotic, and nontwin pairs and (b) within sister pairs using paired t tests.
Cross-sectionally, each additional copy of the HSD3B1 Asn(367)Thr variant allele was associated with lower PMD (-3.47% per allele; SE = 1.65; P = 0.035). Within-pair regression estimates confirmed this association. There was no evidence for an association between the mammographic density measures and any of the other variants studied.
We have replicated an association between a variant in the HSD3B1 gene and PMD, which suggests that HSD3B1 may be genetic determinant of mammographic density.
乳腺X线密度是乳腺X线片上代表结缔组织和上皮组织的浅色/白色影像表现，是乳腺癌的一个强风险因素，且似乎具有高度遗传性。关于其遗传决定因素知之甚少。
我们研究了来自207个姐妹群体的457名女性（104对同卵双胞胎、182对异卵双胞胎和171名单胎女性）。使用计算机辅助方法计算乳腺X线密度百分比（PMD）以及致密区和非致密区。我们测量了6个候选基因（COMT、HSD3B1、IGFBP3、HER2、XPD和XRCC3）的6个单核苷酸多态性。测试了基因型与乳腺X线测量值之间的关联：（a）横断面分析采用FISHER拟合的多元正态模型，该模型允许对同卵双胞胎、异卵双胞胎和非双胞胎对进行单独的相关性分析；（b）在姐妹对中采用配对t检验。
横断面分析中，HSD3B1基因Asn(367)Thr变异等位基因每增加一个拷贝，与较低的PMD相关（每个等位基因降低-3.47%；标准误=1.65；P = 0.035）。配对回归估计证实了这种关联。没有证据表明乳腺X线密度测量值与所研究的任何其他变异之间存在关联。
我们重复验证了HSD3B1基因中的一个变异与PMD之间的关联，这表明HSD3B1可能是乳腺X线密度的遗传决定因素。
