# Novel associations between MTDH gene polymorphisms and invasive ductal breast cancer: a case–control study

## TL;DR

This study finds that certain genetic variations in the MTDH gene are linked to a higher risk of invasive ductal breast cancer.

## Contribution

The study identifies novel associations between specific MTDH gene polymorphisms and increased risk of invasive ductal breast cancer.

## Key findings

- Three MTDH SNPs (rs1311, rs16896059, rs2449512) are significantly associated with increased risk of invasive ductal breast cancer.
- Certain genotypes of these SNPs are linked to higher IDC risk in specific patient subgroups based on age, menopausal status, and tumor characteristics.
- Haplotypes TAA, TAG, and TGG are significantly associated with increased IDC risk compared to the reference haplotype TGA.

## Abstract

To reveal the contributing effects of MTDH gene SNPs in the risk of invasive ductal breast cancer (IDC).

A case–control study was conducted, recruiting a total of 300 cases of IDC and 565 cancer-free controls from East China. Genotyping of three single-nucleotide polymorphisms (SNPs) in the MTDH gene was performed. Genomic DNA was extracted from peripheral blood samples of patients. The three SNPs (rs1311 T > C, rs16896059 G > A, rs2449512 A > G) in the MTDH gene were selected for detection using a TaqMan real-time polymerase chain reaction assay. The association between MTDH and the risk of IDC was analyzed employing an epidemiology case–control study and a multinomial logistic regression model.

Among the three evaluated SNPs, rs1311 T > C, rs16896059 G > A, and rs2449512 A > G demonstrated a significant association with an increased risk of IDC. Furthermore, stratified analysis revealed that individuals carrying the rs1311 CC genotype, rs16896059 GA/AA genotypes, and rs2449512 GG genotype were more susceptible to developing IDC in subgroups of patients younger than 53 years, without family history of IDC, pre-menopause status, clinical stage 2, high grade, with no distant metastasis or invasion, Her2-positive type, ER positive, PR positive, and Ki67 cells less than 10%. However, carriers of the rs16896059 GA/AA genotypes and rs2449512 GG genotype had an elevate the risk of IDC in patients with tumor size larger than 2 cm, post-menopause status, clinical stage 3, with invasion, lymph node infiltration, ER negative, PR negative, Her2 negative, and Ki67 cells exceeding 10%. Compared to the reference haplotype TGA, haplotypes TAA, TAG, and TGG were significantly associated with an increased IDC risk.

In this study, we demonstrated a significant association between MTDH gene polymorphisms and an increased risk of IDC. Moreover, our findings suggested that MTDH gene polymorphisms could serve as a potential biomarker for IDC subtyping and therapeutic selection.