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.
Highlights
In females, breast cancer (BC) has the highest incidence of any cancer worldwide
The present study evaluates the association between specific single-nucleotide polymorphisms (SNPs) and SNP-SNP interactions in the driver genes the functional impact of rs10497520-T (TTN), TBX3, KMT2D, and MAP3K1 with familial and early-onset non-familial BC
In the single-locus analyses, no significant differences were detected for rs702688:A>G or rs702689:G>A genotype or allele distributions, either in the whole dataset or subgroups A or B (p > 0.05)
Summary
Breast cancer (BC) has the highest incidence of any cancer worldwide. At least1.15 million patients are diagnosed annually, comprising about 23% of all cancer cases in women [1,2].Roughly 1 in 8 women alive today will contract BC in their lifetimes [3]. Breast cancer (BC) has the highest incidence of any cancer worldwide. 1.15 million patients are diagnosed annually, comprising about 23% of all cancer cases in women [1,2]. 1 in 8 women alive today will contract BC in their lifetimes [3]. Chile is no exception to these global statistics, as BC has the highest mortality rate among cancers in Chilean women. 1511 deaths in 2015 in this country, with a mortality rate of 16.6 per 100,000 [4,5]. BC incidence is on the rise nationally [5,6]
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