The correlation of leukocyte-specific protein 1 (LSP1) rs3817198(T>C) polymorphism with breast cancer: A meta-analysis

Abstract

Background: Multiple studies have investigated the correlation of single nucleotide polymorphisms (SNPs) in leukocyte-specific protein 1 (LSP1) with susceptibility to breast cancer (BC) and have yielded inconsistent conclusions, particularly rs3817198(T > C). Consequently, we performed a meta-analysis to estimate this relationship more comprehensively.

Methods: Four databases were utilized to locate eligible publications: PubMed, Embase, Web of Science, and China National Knowledge Infrastructure. This meta-analysis included 14 studies, including 22 reports of 33194 cases and 36661 controls. The relationship of rs3817198 polymorphism with breast cancer was estimated using odds ratios (ORs) with 95% confidence intervals (CIs). The LSP1 co-expression network was constructed by STRING, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed using DAVIDE. Download TCGA breast cancer mRNA-seq data and analyze the relationship between LSP1 expression and breast cancer chemotherapy sensitivity.

Results: The results indicated that rs3817198(T > C) was positively correlated to with breast malignancy (dominant model: OR = 1.11, 95%CI = 1.06-1.17; recessive model: OR = 1.10, 95%CI = 1.04-1.15; heterozygous model: OR = 1.09, 95%CI = 1.04-1.15; homozygous model: OR = 1.18, 95%CI = 1.09-1.28; additive model: OR = 1.09, 95%CI = 1.05-1.13), among Caucasians and Asians. However, rs3817198(T > C) may reduce the risk of breast carcinoma in Africans. Rs3817198(T > C) might result in breast carcinoma in individuals with BRCA1 and BRCA2 variants and can contribute to estrogen receptor (ER)-positive breast carcinoma. The expression of LSP1 was inversely correlated with the IC50 of doxorubicin (P = 8.91e-15, Cor = -0.23), 5-fluorouracil (P = 1.18e-22, Cor = -0.29), and cisplatin (P = 1.35e-42, Cor = -0.40).

Conclusion: Our study identified that LSP1 rs3817198 polymorphism might result in breast malignancy, particularly among Caucasians and Asians, but lower breast cancer susceptibility in African populations. The expression of LSP1 was negatively correlated with the IC50 of doxorubicin, 5-fluorouracil, and cisplatin.