Citation: Mathias, C.; Marin, A.M.; Kohler,A.F.; Sanchuki, H.B.S.; Sukow, N.; Beltrame, M.H.; Baal, S.C.S.; Sebastião, A.P.M.; de Souza Fonseca Ribeiro, E.M.; Gradia, D.F.; et al. LncRNA-SNPs in a Brazilian Breast Cancer Cohort: A Case-Control Study. Genes 2023, 14, 971. https:// doi.org/10.3390/genes14050971 Academic Editor: Valeria D’Argenio Received: 2 March 2023 Revised: 18 April 2023 Accepted: 22 April 2023 Published: 25 April 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). genes G C A T T A C G G C A T Article LncRNA-SNPs in a Brazilian Breast Cancer Cohort: A Case-Control Study Carolina Mathias 1,† , Anelis Maria Marin 2,† , Ana Flávia Kohler 1 , Heloisa Bruna Soligo Sanchuki 2 , Natalie Sukow 1 , Marcia Holsbach Beltrame 1 , Suelen Cristina Soares Baal 1 , Ana Paula Martins Sebastião 3 , Enilze Maria de Souza Fonseca Ribeiro 1 , Daniela Fiori Gradia 1 , Mateus Nóbrega Aoki 2, * ,‡ and Jaqueline Carvalho de Oliveira 1, * ,‡ 1 Department of Genetics, Federal University of Parana, Graduate Program in Genetics, Curitiba 81310-020, Brazil 2 Laboratory of Applied Science and Technology in Health, Carlos Chagas Institute, Oswaldo Cruz Foundation (Fiocruz), Curitiba 81310-020, Brazil 3 Department of Pathology, Hospital de Clínicas, Federal University of Paraná, Curitiba 81531-980, Brazil * Correspondence: mateus.aoki@fiocruz.br (M.N.A.); jaqueline.carvalho@ufpr.br (J.C.d.O.) † The authors contributed equally to this work. ‡ The authors jointly directed this work. Abstract: Long noncoding RNAs (lncRNAs) are a class of non-coding RNAs that contain more than 200 nucleotides and exhibit a versatile regulatory capacity. Genomic alterations in lncRNAs have already been investigated in several complex diseases, including breast cancer (BC). BC is a highly heterogeneous disease and is the most prevalent cancer type among women worldwide. Single nucleotide polymorphisms (SNPs) in lncRNA regions appear to have an important role in BC susceptibility; however, little is known about lncRNA-SNPs in the Brazilian population. This study used Brazilian tumor samples to identify lncRNA-SNPs with a biological role in BC development. We applied a bioinformatic approach intersecting lncRNAs that are differentially expressed in BC tumor samples using The Cancer Genome Atlas (TCGA) cohort data and looked for lncRNAs with SNPs associated with BC in the Genome Wide Association Studies (GWAS) catalog. We highlight four lncRNA-SNPs—rs3803662, rs4415084, rs4784227, and rs7716600—which were genotyped in Brazilian BC samples in a case-control study. The SNPs rs4415084 and rs7716600 were associated with BC development at higher risk. These SNPs were also associated with progesterone status and lymph node status, respectively. The rs3803662/rs4784227 haplotype GT was associated with BC risk. These genomic alterations were also evaluated in light of the lncRNA’s secondary structure and gain/loss of miRNA binding sites to better understand its biological functions. We emphasize that our bioinformatics approach could find lncRNA-SNPs with a potential biological role in BC development and that lncRNA-SNPs should be more deeply investigated in a highly heterogeneous disease population. Keywords: rs3803662; rs4415084; rs4784227; rs7716600; breast cancer susceptibility 1. Introduction Breast cancer (BC) is the most common cancer among women worldwide, representing almost 26% of the total number of new cases of cancer diagnosed in 2020 [1]. Several risk factors have been associated with disease development, including environmental factors such as a sedentary lifestyle and alcohol consumption and intrinsic factors related to genetics [2]. Genetic susceptibility to BC can be related to germline mutations with high penetrance, such as those of the BRCA1 and BRCA2 genes, and due to the presence of single nucleotide polymorphisms (SNPs) in coding and non-coding regions [3]. Genes 2023, 14, 971. https://doi.org/10.3390/genes14050971 https://www.mdpi.com/journal/genes