Can cancer GWAS variants modulate immune cells in the tumor microenvironment?
| Autor: | Brittany Baur, Yi Zhang, Shilu Zhang, Jialu Yan, Sushmita Roy, Mohith Manjunath, Jun S. Song |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0303 health sciences
Cell type Tumor microenvironment Tumor-infiltrating lymphocytes Cancer Genome-wide association study Biology medicine.disease 3. Good health 03 medical and health sciences 0302 clinical medicine Immune system 030220 oncology & carcinogenesis Cancer cell medicine Cancer research Epigenetics 030304 developmental biology |
| DOI: | 10.1101/493171 |
| Popis: | Genome-wide association studies (GWAS) have hitherto identified several genetic variants associated with cancer susceptibility, but the molecular functions of these risk modulators remain largely uncharacterized. Recent studies have begun to uncover the regulatory potential of non-coding GWAS SNPs by using epigenetic information in corresponding cancer cell types and matched normal tissues. However, this approach does not explore the potential effect of risk germline variants on other important cell types that constitute the microenvironment of tumor or its precursor. This paper presents evidence that the breast cancer-associated variant rs3903072 may regulate the expression of CTSW in tumor infiltrating lymphocytes. CTSW is a candidate tumor-suppressor gene, with expression highly specific to immune cells and also positively correlated with breast cancer patient survival. Integrative analyses suggest a putative causative variant in a GWAS-linked enhancer in lymphocytes that loops to the 3’ end of CTSW through three-dimensional chromatin interaction. Our work thus poses the possibility that a cancer-associated genetic variant might regulate a gene not only in the cell of cancer origin, but also in immune cells in the microenvironment, thereby modulating the immune surveillance by T lymphocytes and natural killer cells and affecting the clearing of early cancer initiating cells. |
| Databáze: | OpenAIRE |
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