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. 2020 Jan 20;12(1):249.
doi: 10.3390/cancers12010249.

Germline Variants in Driver Genes of Breast Cancer and Their Association with Familial and Early-Onset Breast Cancer Risk in a Chilean Population

Alejandro Fernandez-Moya  1 , Sebastian Morales  1 , Trinidad Arancibia  1 , Patricio Gonzalez-Hormazabal  1 , Julio C Tapia  2 , Raul Godoy-Herrera  1 , Jose Miguel Reyes  3 , Fernando Gomez  4 , Enrique Waugh  4 , Lilian Jara  1
Affiliations

Germline Variants in Driver Genes of Breast Cancer and Their Association with Familial and Early-Onset Breast Cancer Risk in a Chilean Population

Alejandro Fernandez-Moya et al. Cancers (Basel). .

Abstract

The genetic variations responsible for tumorigenesis are called driver mutations. In breast cancer (BC), two studies have demonstrated that germline mutations in driver genes linked to sporadic tumors may also influence BC risk. The present study evaluates the association between SNPs and SNP-SNP interaction in driver genes TTN (rs10497520), TBX3 (rs2242442), KMT2D (rs11168827), and MAP3K1 (rs702688 and rs702689) with BC risk in BRCA1/2-negative Chilean families. The SNPs were genotyped in 489 BC cases and 1078 controls by TaqMan Assay. Our data do not support an association between rs702688: A>G or rs702689: G>A and BC risk. The rs10497520-T allele was associated with a decreased risk in patients with family history of BC or early-onset BC (OR = 0.6, p < 0.0001 and OR = 0.7, p = 0.05, respectively). rs2242442-G was associated with a protective effect and rs11168827-C was associated with increased BC risk in families with a strong history of BC (OR = 0.6, p = 0.02 and OR = 1.4, p = 0.05, respectively). As rs10497520-T and rs2242442-G seemed to protect against BC risk, we then evaluated their combined effect. Familial BC risk decreased in a dose-dependent manner with the protective allele count, reflecting an additive effect (p-trend < 10-4). To our knowledge, this is the first association study of BC driver gene germline variations in a Chilean population.

Keywords: breast cancer risk; driver genes; genetic predisposition to breast cancer; germline variants; single nucleotide polymorphisms.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Protein association network in STRING analysis showing interactions of TBX3, NKX2-5, and TTN. Line colors indicate the mode of action of interaction between proteins.
See this image and copyright information in PMC

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