Association of a LSP1 gene rs3817198T>C polymorphism with breast cancer risk: evidence from 33,920 cases and 35,671 controls

Abstract

Published data on the association between lymphocyte-specific protein 1 (LSP1) rs3817198T>C polymorphism and breast cancer risk are inconclusive. Hence, we conducted a meta-analysis of the LSP1 gene and risk of breast cancer to obtain the most reliable estimate of the association. PubMed, Embase and Web of Science databases were searched. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were extracted and pooled to assess the strength of the association between the LSP1 rs3817198T>C polymorphism and risk of breast cancer. A total of seven eligible studies including 33,920 cases and 35,671 controls based on the search criteria were involved in this meta-analysis. The distributions of genotypes in the controls were all in agreement with Hardy-Weinberg equilibrium. We observed that the LSP1 rs3817198T>C polymorphism was significantly correlated with breast cancer risk when all studies were pooled into the meta-analysis (the allele contrast model: OR = 1.06, 95% CI = 1.04-1.08; the homozygote codominant: OR = 1.14, 95% CI = 1.01-1.28). In the stratified analysis by ethnicity, significant association was observed in Caucasians for CC versus TT homozygote codominant model (OR = 1.25; 95% CI = 1.03-1.52) and for the recessive model (OR = 1.22; 95% CI = 1.02-1.47). There was significant association observed in Africans for CC versus TT homozygote codominant model (OR = 0.45; 95% CI = 0.22-0.92) and for the recessive model (OR = 0.43; 95% CI=0.22-0.88). Also, significant association was observed in mixed ethnicities for CC versus TT homozygote codominant model (OR = 1.12; 95% CI = 1.05-1.19). When stratified by study design, statistically significantly elevated risk was found in nested case-control studies (CC vs. TT: OR = 1.12, 95% CI = 1.05-1.19). But no significant association was observed for all comparison models between LSP1 rs3817198T>C polymorphism and breast cancer risk in hospital-based and people-based studies. When stratified by BRCA1 mutation carriers status, statistically significantly elevated risk was found in this meta-analysis (the allele contrast model: OR = 1.07, 95% CI = 1.01-1.14; the dominant model: OR = 1.09, 95% CI = 1.00-1.18). And significant association was found in the BRCA2 mutation carriers in the allele contrast (OR = 1.11, 95% CI = 1.03-1.20), the homozygote codominant (OR = 1.23, 95% CI = 1.04-1.47), the heterozygote codominant (OR = 1.12, 95% CI = 1.00-1.25) and the dominant models (OR = 1.14, 95% CI = 1.03-1.27). There was significant association between LSP1 rs3817198T>C polymorphism and breast cancer risk in BRCA1 and BRCA2 positive cohort in all comparison models (the allele contrast model: OR = 1.08, 95% CI = 1.03-1.13; CC vs. TT: OR = 1.16, 95% CI = 1.05-1.29; TC vs. TT: OR = 1.09, 95% CI = 1.01-1.16; the dominant model: OR = 1.10, 95% CI = 1.03-1.17; the recessive model: OR = 1.12, 95% CI = 1.01-1.23). In conclusion, this meta-analysis suggests that the LSP1 rs3817198T>C polymorphism is a low-penetrant risk factor for developing breast cancer but may not be in Africans.

LSP1 Gene rs3817198 Polymorphism and Breast Cancer Risk: A Systematic Review and Meta-analysis Study

“…The association between breast cancer and LSP1 gene rs3817198 polymorphism was only significant in homozygote genetic model, which was consistent with results of two previous meta-analyses [26][27]. This result demonstrates that minor allele carries the risk of breast cancer.…”

“…In subgroup analysis, we found the significant association for European & American & African population not Asian in both genetic models. The most recent meta-analysis [27] showed the same results but the earlier [26] documented the association only in homozygote genetic model. Although we categorized the population according to the continent and the two previous meta-analyses based on ethnicity, it makes sense that they considered European and Americans as Caucasian.…”

TheLSP1rs3817198 T > C polymorphism contributes to increased breast cancer risk: a meta-analysis of twelve studies

“…Previously, only one meta-analysis (in 2011) investigated the association between the LSP1 rs3817198 T > C polymorphism and breast cancer risk [ 17 ]. The previous meta-analysis included only 7 studies with 33,920 cases and 35,671 controls and found a significant association between the LSP1 rs3817198 T > C polymorphism and breast cancer under homozygous model and comparison of allele frequencies model.…”

“…However, other studies have failed to replicate such an association [ 14 – 16 ]. Chen et al [ 17 ] conducted a meta-analysis in 2010, and concluded that the LSP1 rs3817198 T > C polymorphism was significantly correlated with breast cancer risk. However, only seven studies were available at that time.…”

Associations between breast density and a panel of single nucleotide polymorphisms linked to breast cancer risk: a cohort study with digital mammography

“…Although association studies such as ours cannot directly inform on or assess underlying biological processes, they do have value in identifying potential pathways of interest that could be interrogated in subsequent studies through hypothesis generation. For example, LSP1 is thought to play a role in mediating neutrophil activation and chemotaxis, and is expressed in both lymphocytes and endothelium [ 78 ], suggesting density may perhaps be, in part, a radiophenotype of genetic risk factors for breast cancer involving tissue vascularization. NEK protein kinases such as NEK10 are thought to play a role in cell cycle regulation [ 79 ] and may be related to breast density via factors related to cellular proliferation.…”