Sartor Hanna, Brandt Jasmine, Grassmann Felix, Eriksson Mikael, Czene Kamila, Melander Olle, Zackrisson Sophia
Diagnostic Radiology, Department of Translational Medicine, Skåne University Hospital, Lund University, Lund, Sweden.
Department of Surgery, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden.
Acta Radiol. 2020 Oct;61(10):1326-1334. doi: 10.1177/0284185119900436. Epub 2020 Feb 9.
Genetic factors are important in determining breast density, and heritable factors account for 60% of the variation. Certain single nucleotide polymorphisms (SNPs) are associated with density and risk of breast cancer but the association with prognosis is not clear.
To investigate associations between selected SNPs and breast cancer survival in the Malmö Diet and Cancer Study (MDCS).
A total of 724 unrelated women with breast cancer and registered radiological and pathological data were identified in MDCS 1991-2007, with genotyping available for 672 women. Associations among 15 SNPs, density, and breast cancer-specific survival were analyzed using logistic/Cox regression, adjusted for factors affecting density and survival. Variants significantly associated with either density or survival were validated in a large independent breast cancer cohort (LIBRO-1).
Minor homozygotes of SNPs rs9383589, and rs6557161, were associated with high breast density (adjusted odds ratio [AOR] 8.97, 95% confidence interval [CI] 1.35-59.57; AOR 2.08, 95% CI 1.19-3.65, respectively) and poorer breast cancer survival (adjusted hazard ratio [HR] 6.46, 95% CI 1.95-21.39; HR 2.30, 95% CI 1.33-3.96, respectively) compared to major homozygotes. For SNP rs3757318, , minor homozygotes (HR 7.46, 95% CI 2.28-24.45) were associated with poorer survival. We confirmed that rs6557161, was significantly associated with both density and survival in the LIBRO-1 study.
These findings support a shared genetic basis for density and breast cancer survival. The SNP significantly associated with both density and survival in both cohorts may be of interest in future research investigating polygenic risk scores for breast cancer risk and screening stratification purposes.
遗传因素在决定乳腺密度方面很重要，遗传因素占变异的60%。某些单核苷酸多态性（SNP）与乳腺密度及乳腺癌风险相关，但与预后的关联尚不清楚。
在马尔默饮食与癌症研究（MDCS）中调查所选SNP与乳腺癌生存之间的关联。
在1991 - 2007年的MDCS中识别出724名患有乳腺癌且有放射学和病理学数据记录的无亲缘关系女性，其中672名女性可进行基因分型。使用逻辑/ Cox回归分析15个SNP、乳腺密度和乳腺癌特异性生存之间的关联，并对影响密度和生存的因素进行校正。在一个大型独立乳腺癌队列（LIBRO - 1）中验证与密度或生存显著相关的变异。
SNP rs9383589和rs6557161的次要纯合子与高乳腺密度相关（校正比值比[AOR]分别为8.97，95%置信区间[CI] 1.35 - 59.57；AOR 2.08，95% CI 1.19 - 3.65），与较差的乳腺癌生存相关（校正风险比[HR]分别为6.46，95% CI 1.95 - 21.39；HR 2.30，95% CI 1.33 - 3.96），与主要纯合子相比。对于SNP rs3757318，次要纯合子（HR = 7.46，95% CI 2.28 - 24.45）与较差的生存相关。我们在LIBRO - 1研究中证实rs6557161与密度和生存均显著相关。
这些发现支持乳腺密度和乳腺癌生存存在共同的遗传基础。在两个队列中均与密度和生存显著相关的SNP可能在未来研究乳腺癌风险的多基因风险评分和筛查分层方面具有研究价值。
