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瑞典全基因组单倍型关联分析揭示具有不同风险修饰效应的乳腺癌基因座。

Swedish Genome-Wide Haplotype Association Analysis Suggests Breast Cancer Loci with Varying Risk-Modifying Effects.

作者信息

Vermani Litika, Barnekow Elin, Liu Wen, Wendt Camilla, Hall Per, Margolin Sara, Lindblom Annika

机构信息

Department of Molecular Medicine and Surgery, Karolinska Institutet, 17176 Stockholm, Sweden.

Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, 11883 Stockholm, Sweden.

出版信息

Genes (Basel). 2024 Dec 17;15(12):1616. doi: 10.3390/genes15121616.

Abstract

To find support for risk-modifying genes in breast cancer, a haplotype GWAS in sporadic breast cancer cases was undertaken. The results were compared with the results from previous analyses in familial cases and all cases from the same Swedish cohort. In total, 2550 women with sporadic invasive breast cancer and 5021 healthy controls were included in a sliding-window haplotype GWAS using PLINK 1.07. The analysis of sporadic cases confirmed the loci on chromosomes 10q26.13, 11q13.3, and 16q12.1 and suggested one novel locus on chromosome 12p11.21 (OR = 1.42 = 4.55 × 10). A comparison between these loci and the same loci in the analyses of familial cases and all breast cancer cases was undertaken. Haplotype GWAS in sporadic cases of Swedish breast cancer cases supported known risk loci and suggested another risk locus. The loci identified in the analysis of sporadic and all breast cancer cases were suggested to act as modifiers of the risk of breast cancer. Haplotype analysis identified other loci with higher odds ratios than single-variant analysis. Further studies are needed to find out how to best include the findings in breast cancer prevention.

摘要

为了寻找乳腺癌中风险修饰基因的证据,我们对散发性乳腺癌病例进行了单倍型全基因组关联研究(GWAS)。将结果与之前对家族性病例以及来自同一瑞典队列的所有病例的分析结果进行了比较。总共2550名散发性浸润性乳腺癌女性和5021名健康对照被纳入使用PLINK 1.07进行的滑动窗口单倍型GWAS研究。对散发性病例的分析证实了10q26.13、11q13.3和16q12.1染色体上的位点,并提示了12p11.21染色体上的一个新位点(OR = 1.42,P = 4.55×10)。对这些位点与家族性病例和所有乳腺癌病例分析中的相同位点进行了比较。瑞典乳腺癌散发性病例的单倍型GWAS研究支持了已知的风险位点,并提示了另一个风险位点。在散发性和所有乳腺癌病例分析中确定的位点被认为是乳腺癌风险的修饰因子。单倍型分析确定了其他比值比高于单变量分析的位点。需要进一步研究以找出如何最好地将这些发现纳入乳腺癌预防中。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/751c/11675172/67bf288e0832/genes-15-01616-g001.jpg

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