Developmental Biology - Immune System|
Breast Cancer Gene Affects Immune Response
Altering SH2B3 gene links to decrease in immune cell response to malignancies...
The idea that the immune system "monitors and prevents" development of cancer, known as "cancer immune vigilance", was first suggested at the beginning of the last century. Since then, epidemiological studies show suppression of our immune system increases our risk for cancer. However, the molecular basis for this still isn't well understood.
Now, a study led by the ProCURE program of the Catalan Institute of Oncology (ICO), and the OncoBell program of the Bellvitge Biomedical Research Institute (IDIBELL), has identified gene variations predisposing an individual to cancer by altering that person's immune response.
Scientists analyzed 17 types of cancer to find thirteen with as many as 57 genetic variants predisposed to cancer and affecting the body's defense system.
The article is published in the Cell Press journal iScience.
"The results suggest the risk of developing cancer can be explained, in part, by alterations in the number of immune cells.
If we identify the effect these gene variants have on the immune system, we can design new prevention strategies for patients with a high risk of developing that cancer — by modulating specific functions of immune system cells."
Miquel Pujana PhD, Project Leader for ProCURE Program, Catalan Institute of Oncology and Oncobell Program, Bellvitge Biomedical Research Institute.
One of the specific connections identified by this study is the relationship between the SH2B3 gene, a lymphocyte protein, with a high risk for breast cancer. Particularly in women with mutations in both BRCA1 and BRCA2 genes. Histochemical studies corroborate that alteration of the SH2B3 gene is related to lower infiltration by immune cells in tumor tissue.
In the presence of an SH2B3 gene variant, there are also fewer lymphocytes in peripheral blood, which is related to a diagnosis of cancer at younger ages.
"These indications lead us to think that correcting function of the SH2B3 gene is decisive in protecting women carrying BRCA1/2 mutations. Pharmacological induction of the SH2B3 gene might reduce risk for cancer."
Miquel Angel Pujana PhD.
The Immune System In the Development of Cancer
The immune system recognizes foreign microorganisms as "not self" and responds by destroying these disease causing agents, protecting the body against malignancies. Damaged DNA from cancer cells eventually induces production of abnormal proteins known as tumor antigens — which also mark abnormal tumor proteins as "not self."
The immune system can find and kill cancer cells, but clearly, cancer cells have mechanisms that allow them to escape immune responses that usually prevent development of malignant tumors. When the immune system loses its surveillance function, tumor cells form.
Proper immune system function hinders cancer development, but little is known about whether genetic variants linked to cancer risk alter immune cells. Here, we report 57 cancer risk loci associated with differences in immune and/or stromal cell contents in the corresponding tissue. Predicted target genes show expression and regulatory associations with immune features. Polygenic risk scores also reveal associations with immune and/or stromal cell contents, and breast cancer scores show consistent results in normal and tumor tissue. SH2B3 links peripheral alterations of several immune cell types to the risk of this malignancy. Pleiotropic SH2B3 variants are associated with breast cancer risk in BRCA1/2-mutation carriers. A retrospective case-cohort study indicates a positive association between blood counts of basophils, leukocytes, and monocytes, and age at breast cancer diagnosis. These findings broaden
our knowledge of the role of the immune system in cancer and highlight promising prevention strategies for individuals at high risk.
Luis Palomero, Ivan Galván-Femenía, Rafael de Cid, Roderic Espín, Daniel R.
Barnes, CIMBA, Eline Blommaert, Miguel Gil-Gil, Catalina Falo, Agostina Stradella,
Dan Ouchi, Albert Roso-Llorach, Concepció Violan, María Peña-Chilet, Joaquín
Dopazo, Ana Isabel Extremera, Mar García-Valero, Carmen Herranz, Francesca
Mateo, Elisabetta Mereu, Jonathan Beesley, Georgia Chenevix-Trench, Cecilia Roux,
Tak Mak, Joan Brunet, Razq Hakem, Chiara Gorrini, Antonis C. Antoniou, Conxi
Lázaro and Miquel Angel Pujana.
This study has been possible thanks to the support of various patient associations in Catalonia from IDIBELL and ICO, especially the Viladecans Against Cancer associations, Association of Women Affected by Breast Cancer (DACMA, Sant Joan Despí), Association of Cancer Affected GINKGO (Barcelona), and the Sosciathlon solidarity day.
University of Cambridge, UK.
"Princess Margaret" Cancer Research Center, Canada.
QIMR Berghofer Institute for Biomedical Research, Brisbane, Australia.
University Institute for research in Primary Health Care Jordi Gol y Gurina (IDIAPJGol)
GCAT Project, Genomes for Life, Germans Trias y Pujol Research Institute (IGTP).
National Center for Genomic Analysis (CNAG-CRG).
Clinical Bioinformatics Area, Fundación Salud y Progreso, Junta de Andalucía.
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The risk of developing cancer can be explained, in part, by a reduction
in the number of immune cells. CREDIT The Authors.