Genetic structures predict adverse response to chemotherapy in breast cancer patients

Certain genetic structures among patients with breast cancer are associated with adverse response to chemotherapy, reports a recent study.

Six genetic variants (ie, rs3820706, rs147451859, rs4784750, rs17587029, rs16830728, and rs16972207) significantly predicted response to chemotherapy in breast cancer patients (p<5 x 10^-8), and seven novel haplotypic structures were found to be associated with adverse response to chemotherapy.

Such haplotypes formed two genetic structures that correlated with neutropenia, leukopenia, chemotherapy-induced cytotoxicity (GAG-TTAT) and chemotherapy-induced alopecia (CC-CAACTCCCGTTGCGG). These variants were found on PPCDC, NLRC5, STAM2, and TNFSF13B genes.

The expression of these genes resulted in a significant change in breast cancer tissues compared with normal tissues (p≤0.05), indicating gene-gene correlation (p≤0.05). 

“These genetic variants and their associated novel haplotypic structures can predict adverse response to chemotherapy in BC patients and could potentially form BC-associated genetic panel for adverse response to chemotherapy,” the researchers said.

In this study, the research team obtained significant variants associated with response to chemotherapy from genome-wide association studies and identified candidate variants by haplotype analysis using 1000Genome LD data. They also assessed the expression quantitative trait loci to determine the effects of the variants on gene expression.

Finally, expression levels were compared between TCGA tumour types and adjacent normal tissues to evaluate the expression of the identified genes in the tumour sample.