top of page
  • Ng En Ze

Genetic Predisposition: Are Genes Fate?

Updated: Nov 11, 2022

This article was submitted by a reader and edited by The STEM Bulletin.



Among multiple possible factors of human diseases, family history sometimes appears to be one of the strongest risk factors for common complex diseases such as cancer, cardiovascular disease, Type 2 diabetes, autoimmune diseases such as lupus and rheumatoid arthritis and certain psychiatric illnesses such as schizophrenia and bipolar disorder.⁴ Genetic predisposition, also known as genetic susceptibility², is often the reason behind the familial patterns of these diseases.


In general, genetic predisposition implies that there is an increased chance for an individual to develop a particular disease based on their genetic makeup. Most of the time, this genetic makeup results from inheritance of specific variations that differ from the ‘standard’ form of a particular gene that most people have, making the individual more vulnerable to a disease under the right set of contributing factors.⁶ Besides the aforementioned diseases, there are hundreds of other diseases that are known or believed to be influenced by genetic predisposition as well. Beyond diseases, conditions such as addiction and even one’s temperament can also be influenced by genetic predisposition.²


One example of a common disease involving genetic predisposition is breast cancer. There are a wide range of genes with different penetrance levels that are involved in breast cancer such as the BRCA1 gene, BRCA2 gene and BRIP1 gene, among others. The BRCA1 gene located on chromosome 17q21.31¹ is one of the best-known high penetrance genes associated with breast cancer. This gene is considered a tumor suppressor gene (also known as an anti-oncogene) which is responsible for providing instructions for the production of the BRCA1 protein, a tumor suppressor protein.⁷ The BRCA1 protein is responsible for repairing damaged DNA and interacts with other proteins to mend breaks in DNA strands that occur when chromosomes exchange genetic material during cell division or upon exposure to radiation.⁵ This means that any change in BRCA1 gene may lead to increased risk of developing cancers, since a mutated BRCA1 gene can lead to abnormal or inadequate BRCA1 proteins. When this happens, damaged DNA cannot be repaired. When these defects in DNA accumulate, cells may start to grow and divide rapidly and uncontrollably, forming a tumor. This illustrates how people who have a specific pathogenic or mutated variant of BRCA1 gene are genetically predisposed to breast cancer.


Based on an investigation (Angeli et al., 2020), germline pathogenic variants in BRCA1 gene are associated with a 57 to 65% risk of developing breast cancer by the age of 70. Moreover, the BRCA1 pathogenic or likely-pathogenic variants are also associated with an estimated 1.2% increased risk of breast cancer in males by the age of 70. Besides the BRCA1 gene, people who possess pathogenic likely-pathogenic variants of other genes associated with breast cancer such as the BRCA2 gene, TP53 gene and PTEN gene also show increased risk of developing breast cancer during their lifetime.¹ To summarize, people who have the pathogenic variant or mutation in genes associated with the development of breast cancer (in other words, those who are genetically predisposed to breast cancer) will have a significantly higher risk of developing breast cancer. However, genetics are not the sole determinant of the disease as other environmental and lifestyle factors can affect a person’s risk of developing breast cancer.


Unlike genetic diseases, a person who is genetically predisposed to a certain disease will not necessarily develop the disease; it simply means that the person is more likely to develop the disease under certain circumstances. In other words, genetic predisposition is as if a light switch, one can have control over it by preventing other risk factors that will contribute to the development of the disease he or she is predisposed to. Genetic predisposition can be revealed by genetic testing, and early prevention can significantly reduce the risk of developing a particular disease.⁸


There is evidence that people who are predisposed to obesity do not become overweight when they practise a healthy lifestyle. According to the Harvard School of Public Health, there are multiple genes linked with obesity, one of which is the is the fat mass and obesity-associated (FTO) gene on chromosome 16 which is rather common within the population, and people who carry the obesity-promoting variant of the FTO gene have a 23% higher risk of obesity than those who do not. However, not everyone with the obesity-promoting FTO gene becomes overweight. Those who practice healthy lifestyles and are physically active do have reduced risk of being obese. Based on the data collected, physically active adults with the obesity-promoting FTO gene have a 30% lower risk of obesity than physically inactive adults with the gene.³ This suggests that a healthy lifestyle is able to counteract the effects of genetics.


At the end of the day, genes are not fate. A person’s genetic makeup cannot be altered, but common contributing factors to disease such as smoking, alcohol abuse and long-term sleep deprivation can be avoided by practicing a healthy and disciplined lifestyle to reduce disease risk in people, even among those with a genetic predisposition towards particular diseases.


 

Reference:

  1. Angeli, D., Salvi, S. & Tedaldi, G. (2020). Genetic predisposition to breast and ovarian cancer: How many and which genes to test?. International Journal of Molecular Science 2020, 21(3), 1128. https://doi.org/10.3390/ijms21031128

  2. Dellwo, A. (2020, December 12). Genetic predisposition: What it is, what it means to you. Verywell Health. https://www.verywellhealth.com/genetic-predisposition-5087879

  3. Harvard School of Public Health. (n.d.). Genes are not destiny. https://www.hsph.harvard.edu/obesity-prevention-source/obesity-causes/genes-and-obesity/

  4. Hernandez, L. M. & Blazer, D. G. (Eds.). (2006). Genes, behavior and the social environment: Moving beyond the nature/nurture debate. National Academies Press (US). https://www.ncbi.nlm.nih.gov/books/NBK19932/

  5. Medline Plus. (2020, May 1). BRCA1 gene. https://medlineplus.gov/genetics/gene/brca1/

  6. Medline Plus. (2021, May 14). What does it mean to have a genetic predisposition to a disease?. https://medlineplus.gov/genetics/understanding/mutationsanddisorders/predisposition/

  7. Mehrgou, A. & Akouchekian, M. (2016). The importance of BRCA1 and BRCA2 genes mutation in breast cancer development. Medical Journal of the Islamic Republic of Iran. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4972064/

  8. NHS. (2019, September 3). Genetic and genomic testing. https://www.nhs.uk/conditions/genetic-and-genomic-testing/

53 views0 comments

Recent Posts

See All

Comments


bottom of page