Contributor Saniyah Qureshi
There are several general risk factors in developing cancer, some of which include tobacco use, alcohol intake, and radiation exposure. However, when compared to Chimpanzees who are genetically closest to homo sapiens, we are exceptionally susceptible to developing advanced carcinomas (cancers that stem from epithelial cells) despite the absence of risk factors.
Researchers from the University of California San Diego discovered that evolutionary genetic mutation may be the link when rooting advanced cancers found in humans. The study examines the relationship between advanced carcinomas and the Siglec-12 protein-encoding gene. Seeing that humans continue to evolve, in the past, the Siglec-12 protein underwent a mutation that removed its ability to decipher attacking microbes and so, the body’s response was to automatically eliminate it. Therefore, the ability to produce Siglec-12 has been lost in a large portion of the human population. MD Ajit Varki claims that after this mutation, “the dysfunctional form of the Siglec-12 protein...has now become a liability for the minority of people who still produce it.”
From comparing samples of adjacent normal and malignant tissues, Siglec-12 expression was highest in those with the malignant cells. Also, of the 30% who can produce Siglec-12, they are twice at risk for developing a type of advanced carcinoma. MD and professor of pathology, Nissi Varki and her team investigated the Siglec-12 protein in the non-cancerous tissue samples by employing antibodies that work against the protein. They reported that only 30% of the samples were positive for Siglec-12 due to genetic information. When the cancerous tissues were tested, the results were to no surprise that the majority of the collected samples contained the Siglec-12 protein.
The study was then replicated and tested with a different population who were undergoing an advanced stage of colorectal cancer. They discovered that more than 80% of the population consisted of the functional form of Siglec-12 and those that did had poorer aftereffects. Nissi Varki was able to observe and conclude from the data that the minority of individuals who are still able to produce the Siglec-12 gene have a higher chance of developing a type of progressive cancer.
Another study was done to generalize the findings, this time on mice. Tumour cells that were designed to develop Siglec-12 were injected into mice and resulted in cancer spreading at a faster rate. Remarkably, when compared to the control group, this reaction resulted in activating biological pathways that are “known to be involved in advanced cancers.”
In light of this information, researchers can further understand the underlying roots of advanced cancers as well as potentially designing future treatments. Interestingly enough, researchers have recently developed a urine test that is able to identify Siglec-12. From this study, MD Ajit Varki has hopes in the future to be able to use “antibodies against Siglec-12 to selectively deliver chemotherapies to tumor cells that carry the dysfunctional protein, without harming non-cancerous cells.” From just understanding the structure and function of Siglec-12, scientists are a step closer to making groundbreaking discoveries that may progress diagnoses as well as treatments for advanced cancers.
Article Reference:
“Evolution May Be to Blame for High Risk of Advanced Cancers in Humans.” ScienceDaily, ScienceDaily, 9 Dec. 2020, www.sciencedaily.com/releases/2020/12/201209094241.htm.
Journal Reference:
Shoib S Siddiqui et al. Human‐specific polymorphic pseudogenization of SIGLEC12 protects against advanced cancer progression. FASEB BioAdvances, 08 December 2020 DOI: 10.1096/fba.2020-00092