Genetic Variants and Cancer Susceptibility

Inherited and acquired genetic variants underlie differences in individual susceptibility to cancer by altering the function or regulation of genes involved in cell proliferation, DNA repair and apoptosis. Single nucleotide polymorphisms (SNPs), structural rearrangements and mutations in regulatory regions can affect the expression of oncogenes and tumour suppressor genes. Advances in genome-wide association studies, next-generation sequencing and bioinformatic analysis have enabled the identification of polygenic risk profiles and the discovery of functional variants that modulate cancer risk across diverse populations. Many susceptibility loci exert their effects through changes in gene regulation mediated by microRNAs or epigenetic modifiers, highlighting the interplay between inherited variation and post-transcriptional control. The global significance of this work lies in its potential to inform personalised screening strategies, refine risk prediction models and guide the development of targeted prevention measures.

Research from Nature Portfolio

Foundational studies have elucidated how polymorphisms in microRNA regulatory regions contribute to tumour initiation and progression. A functional variant in the flanking region of the miR-143/145 cluster was shown to increase colorectal cancer risk by reducing microRNA expression and thereby deregulating cell-cycle control. Research into the miR-16–KRAS axis demonstrated that loss of miR-16 repression leads to elevated KRAS protein levels, promoting proliferation and invasion of colorectal tumour cells; restoration of this axis in xenograft models inhibited tumour growth. In oesophageal squamous cell carcinoma, a variant within the miR-502 binding site of the histone methyltransferase SET8 modulates SET8 expression, with the protective allele reducing tumour cell invasion and enhancing apoptosis. These studies collectively highlight microRNA-mediated regulatory mechanisms as key determinants of cancer susceptibility.

Genetic Variants and Cancer Susceptibility publication trend

The graph below shows the total number of articles in genetic variants and cancer susceptibility across all publications each year (not limited to Nature Index journals).

Technical terms

Single Nucleotide Polymorphism (SNP): A variation at a single base pair in the DNA sequence that may alter gene function or regulation.

microRNA (miRNA): A small non-coding RNA molecule that regulates gene expression post-transcriptionally, often by binding to the 3′ untranslated region of target mRNAs.

3′ Untranslated Region (3′ UTR): The non-coding segment of an mRNA downstream of the coding sequence, containing regulatory elements that influence mRNA stability and translation.

Oncogene: A gene that, when mutated or overexpressed, can drive the transformation of a normal cell into a tumour cell.

References

1. Additional prognostic value of polymorphisms within the 3′-untranslated region of programmed cell death pathway genes in early-stage breast cancer. Frontiers in Immunology (2024).
2. Association of the rs8720 and rs12587 KRAS Gene Variants with Colorectal Cancer in a Mexican Population and Their Analysis In Silico. Cells (2023).
3. MicroRNA-Mediated Regulation of Histone-Modifying Enzymes in Cancer: Mechanisms and Therapeutic Implications. Biomolecules (2023).
4. A functional variant rs353292 in the flanking region of miR-143/145 contributes to the risk of colorectal cancer. Scientific Reports (2016).
5. miR-502 medaited histone methyltransferase SET8 expression is associated with outcome of esophageal squamous cell carcinoma. Scientific Reports (2016).
6. Deregulation of the miR-16-KRAS axis promotes colorectal cancer. Scientific Reports (2016).