Novel Association of IGF2BP2 Gene Variants With Altered Risk of Breast Cancer and as Potential Molecular Biomarker of Triple Negative Breast Cancer

• Published in: Clinical breast cancer Vol. 23; no. 3; pp. 272 - 280
• Main Authors: Almawi, Wassim Y., Zidi, Sabrina, Sghaier, Ikram, El-Ghali, Rabeb M., Daldoul, Amira, Midlenko, Anna
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-04-2023
• Subjects: Biomarkers; Breast Neoplasms - genetics; Case-Control Studies; Contraceptives, Oral; Diabetes Mellitus, Type 2; Female; Genetic Predisposition to Disease; Genomics; Genotypes; Haplotypes; Hormone cancers; Humans; Insulin-like growth factor 2 mRNA binding protein 2; RNA-Binding Proteins - genetics; Triple Negative Breast Neoplasms - genetics; Haplotypes; BC; LN; PR; OR; Genomics; CI; IGF2; ER; HER/2-neu; Hormone cancers; Insulin-like growth factor 2 mRNA binding protein 2; IGF2BP2; TNBC; Genotypes
• ISSN: 1526-8209; 1938-0666
• DOI: 10.1016/j.clbc.2022.12.017

•Minor allele of rs440960, but not rs1470579, was significantly associated with breast cancer (BC).•Significantly higher rs4402960 T/T genotype frequency was noted in BC cases.•Lower rs1470579 minor allele and genotype frequencies seen in triple negative BC (TNBC) cases.•Both susceptible and protective 2-locus haplotypes associated with TNBC.
We investigated the association of IGF2BP2 polymorphisms with breast cancer (BC) and triple negative BC (TNBC). This study included 130 TNBC, 358 non-TNBC BC patients and 476 cancer-free controls. While rs440960 IGF2BP2 polymorphism was positively associated with BC, both rs4402960 and rs1470579 variants were negatively associated with TNBC. We propose novel diagnostic/prognostic role for IGF2BP2 polymorphisms in BC and TNBC.
Several studies documented that insulin-like growth factor-2 mRNA-binding protein 2 (IGF2BP2) contributes to carcinogenesis, and 1 report documented the association of IGF2BP2 rs4402960 with increased risk of breast cancer (BC). This study investigated the association of rs4402960 and rs1470579 IGF2BP2 variants with BC and triple negative BC (TNBC).
This case-control study included 488 BC patients comprising 130 TNBC and 358 non-TNBC patients, and 476 cancer-free controls. Genomic DNA was obtained from peripheral venous blood, and genotyping was done by allelic exclusion method on real-time PCR.
The rs440960, but not rs1470579, minor allele was significantly associated with BC, and significantly higher rs4402960 T/T genotype frequency was noted in BC patients than controls; the distribution of rs1470579 genotypes were comparable between BC patients and controls. In contrast, significantly lower rs1470579 minor allele frequency, and reduced rs1470579 A/C and C/C, and rs4402960 T/T genotype frequencies were seen in TNBC cases. Among TNBC cases, rs4402960 and rs1470579 correlated with menses pattern, histological type, breastfeeding, oral contraceptive use and hormonotherapy. Among non-TNBC patients, and rs1470579 correlated significantly with breast feeding, oral contraceptive use, hormonotherapy, and nodal status; rs4402960 also correlated with menses pattern. Two-locus (rs440960-rs1470579) haplotype analysis confirmed the positive association of TC, and negative association of GC and TA haplotypes with BC, while TC and GC haplotypes were negatively associated with TNBC.
Whereas rs440960 was positively associated with BC, both rs4402960 and rs1470579 were negatively associated with TNBC, suggesting potential diagnostic/prognostic role in BC and its complications.