Mammographic features influence breast cancer risk and are used in risk prediction models. Understanding how genetics influence mammographic features is important because the mechanisms through which they are associated with breast cancer are not well known. Here, using mammographic screening history and detailed questionnaire data from 56,820 women from the KARMA prospective cohort study, we investigated the association between a genetic predisposition to breast cancer and mammographic features among women with a family history of breast cancer ( N = 49,674) and a polygenic risk score (PRS, N = 9,365). The heritability of mammographic features such as dense area (MD), microcalcifications, masses, and density change (MDC, cm2/year) was estimated using 1,940 sister pairs. Heritability was estimated at 58% [95% confidence interval (CI), 48%–67%) for MD, 23% (2%–45%) for microcalcifications, and 13% (1%–25%)] for masses. The estimated heritability for MDC was essentially null (2%; 95% CI, −8% to 12%). The association between a genetic predisposition to breast cancer (using PRS) and MD and microcalcifications was positive, while for masses this was borderline significant. In addition, for MDC, having a family history of breast cancer was associated with slightly greater MD reduction. In summary, we have confirmed previous findings of heritability in MD, and also established heritability of the number of microcalcifications and masses at baseline. Because these features are associated with breast cancer risk and can improve detecting women at short-term risk of breast cancer, further investigation of common loci associated with mammographic features is warranted to better understand the etiology of breast cancer. Significance: These findings provide novel data on the heritability of microcalcifications, masses, and density change, which are all associated with breast cancer risk and can indicate women at short-term risk.

中文翻译：

---

乳腺X线摄影密度，密度变化，微钙化和肿块的遗传力

乳腺摄影特征会影响乳腺癌的风险，并用于风险预测模型中。了解遗传学如何影响乳腺X线摄影特征很重要，因为它们与乳腺癌相关的机制尚不清楚。在这里，我们使用了X线筛查史和来自KARMA前瞻性队列研究的56,820名妇女的详细调查表数据，我们调查了具有乳腺癌家族史（N = 49,674）的女性中，乳腺癌的遗传易感性与X线特征之间的关联。多基因风险评分（PRS，N = 9,365）。乳腺X线摄影特征的遗传力，如致密区域（MD），微钙化，肿块和密度变化（MDC，cm2 /年）使用1,940对姊妹对进行了估计。遗传力估计为58％[95％置信区间（CI），MD占48％–67％，微钙化占23％（2％–45％），质量占13％（1％–25％）]。MDC的估计遗传力基本上为零（2％； 95％CI，−8％至12％）。乳腺癌的遗传易感性（使用PRS）与MD和微钙化之间的关联为阳性，而对于大众而言，这具有临界意义。此外，对于MDC，有乳腺癌家族史的患者MD下降幅度更大。总而言之，我们已经确认了MD中遗传性的先前发现，并且还确定了基线时微钙化和肿块的遗传性。由于这些功能与罹患乳腺癌的风险有关，并且可以改善对有乳腺癌短期风险的女性的检测，为了进一步了解乳腺癌的病因，有必要进一步调查与乳腺X线摄影特征有关的常见基因座。启示：这些发现提供了关于微钙化，肿块和密度变化的遗传性的新数据，这些遗传性都与患乳腺癌的风险有关，并且可以表明女性处于短期风险中。