Genetics in cancer

Megan Scott helps us understand how genetics play a role in developing cancer and the different types of mutations you can get.

Genetic knowledge of human disease holds the promise for personalised and precision medicine. The theory behind this is that knowing the role of genetics in disease development provides insight into the way diseases occur and unique options for targeted treatment. Likewise, knowledge of an individual’s genetic profile identifies risk, access to targeted preventative measures and maximises treatment efficiencies.  

The role of genetics in cancer risk, development and treatment has advanced greatly over the past 30 years and is ultimately moving towards this promise. Genetics, the terminology and its role in cancer development is complex. Understanding these intricacies is of value in navigating this knowledge and what it means to you. The way to do this is go back to basics and build on this foundation.

Genetics 101

Genetics refers to information stored in every cell of our body. It contains the instruction or ‘recipe’ for all the substances that make us (what we look like, how we function and where we are in our life stages).

The structure of genetic information is made up of a unique alphabet (DNA code) that consists of four chemical letters or bases. These bases occur in a unique sequence and are the instruction for substances needed by our bodies. An instruction is a section of the DNA sequence and is referred to as a gene; a gene is a ‘recipe’ for something we need.  

These DNA sequences are neatly packaged into structures called chromosomes. Think of a chromosome as a book, written in a different code and each consists of a 1 000 chapters (genes). The genetics of a human is stored in 46 chromosomes; 23 pairs as we get one from each parent. This tells us that in most instances we have two copies of a gene, one from our mother and one from our father, and for optimal function we need both genes to be functioning.


Genetics also plays a role in inheritance, what is passed from one generation to the next. Humans need to start with 46 chromosomes, meaning that each parent can only pass down half of their chromosomes, one from each pair. This is the simple clue into inheritance. There are different patterns of inheritance depending on how traits express because of a gene.

The conformation of genetic information offers insight into genetics and disease. Changes on the different levels of our genetic structure impacts health. From chromosomes disorders, resulting from a loss or gain of a whole or part of a chromosome, to changes in the DNA code of a gene or multiple genes. Chromosome disorders can lead to cancer but for now we will be focusing on changes at the level of DNA. 

Our initial knowledge of inheritance of traits and ultimately disease is based on the work of Gregor Mendel in 1865. He noted differences in pea plants based on the parent plants. This provided insight into expression of genes and a clue regarding rare single gene disorders.  

Single gene disorders

Single gene disorders result from changes (mutations) in the DNA code of a gene, impacting its function which can lead to disease. Single gene disorders are also called Mendelian conditions, based on inheritance patterns. The inheritance pattern is defined by the presentation of the disease, based on whether one or both of a gene carries a mutation and, in some instances, which chromosome the gene is located. Giving us the patterns of inheritance: recessive, dominant or X-linked.

The Human Genome Project (HGP)  

Our understanding of the role of genetics in disease has developed substantially over the past 20 years since the completion of HGP. The project decoded the human genome, all the DNA bases (>3 billion letters) and its sequence, based on the premise that variance in the DNA sequence is a key to understanding disease.  

Research using this precept mostly included two groups of individuals: those with the condition and the general population. Patterns of change were identified and in doing so single and even multiple genes were identified, their function elucidated and the impact of changes within the code, providing context for a deep understanding of disease development. Profiles of genetic variance were identified that could infer risk.

Genes that cause cancer risk 

There are different variants on the DNA level that are significant to cancer risk assessment, prevention and treatment.

Germline mutations – hereditary breast cancer

Hereditary cancer syndromes are single gene disorders that result in an increased risk for cancer to develop. The knowledge of such a condition is used for people to access support to prevent the impact of cancer in their lives and that of their family.

The first insight into a hereditary cancer syndrome was, in 1990, when Dr Mary-Claire King suggested a hereditary risk factor for breast and ovarian cancer in certain families. A year later the BRCA1 gene was identified and a few years later the BRCA2 gene.

These genes are cancer suppressor genes, in that the product of these genes prevents the development of tumours. We all have two copies of each. 

A mutation in the DNA code of one of these genes impacts its function to protect and leads to an increase in the propensity for cancer to develop.  

As an example, a woman born with a mutation in one BRCA1 gene is said to have hereditary breast and ovarian cancer syndrome. Her risk for breast and ovarian cancer and others is far greater than the general population. Inheritance is dominant, meaning there is a 50% risk to each of her children to inherit regardless of their gender.  

The mutation here is called a germline mutation, meaning it came from conception and was present at birth and is represented throughout all the body’s cells.

Knowledge of these hereditary cancer syndromes has enabled individuals and their families to access intensive screening and management and sometimes prophylactic surgery to reduce the impact of cancer.

Summary of germline mutations: single gene disorder 

DNA mutation impacts the functioning of the gene

Genes: Tumour suppressor genes and related genes

Genetic test: Diagnostic to detect a mutation

Reason for testing: High risk for a hereditary cancer syndrome based on family or personal cancer history

Risk profile: High risk for cancer to occur, 4-6 times greater

Inheritance: Yes, and mostly dominant, 50% risk to next generation

Prevalence: Rare, impacting about 5-10% families

Guidelines: Clinical guidelines for cancer surveillance, management and prevention and treatment guidelines

Examples: Genetic testing of the BRCA1 and BRCA2 genes

Sporadic risk – polygenic risk score

The diagnosis of most cancers is considered to be sporadic and the cause a complex interaction of multiple environmental risk factors and genes.  

The genetic risk portion is referred to as polygenic risk. There are changes or variants in the DNA code of many genes that create a profile which may be interpreted into a general risk. No single gene is causative and the risk for cancer is slightly elevated compared to that of the general population. The changes are not mutations, meaning they don’t impact the overall function of the gene. 

The knowledge of polygenic risk is based on recent research, and how to translate this information into practice and management guidelines to reduce the risk of cancer occurrence is still being reviewed.

Genetic testing is available through research and some laboratories and involves the detection of multiple predefined variants in multiple genes, and then algorithms are applied to confer a risk profile in comparison to the general population risk.

Summary of polygenic risk: sporadic cancer

DNA changes don’t completely alter or impact function of gene

Genes: Multiple genes with multiple variants 

Genetic test: Genomic profiling of multiple variants in multiple genes

Reason for testing: General risk profile

Risk profile: Small changes in overall risk

Inheritance: Not specific but familial

Prevalence: Common

Guidelines: Research into suggested surveillance guidelines

Tumour profiling – somatic mutations

Germline mutations and polygenic profiles refer to genetic changes that are present at birth. In reality as we age and are exposed to various environmental risk factors, we ‘pick up’ mutations along the way. These are termed as somatic (in the body) mutations.

Somatic mutations aren’t represented throughout the body. These result from an error occurring in the DNA code of a cell. 

As a cell that contains this error replicates and these cells proliferate these mutations persist. Depending on where in the genetic code these mutations occur, could result in the development of cancer.  

Genetic testing of tumours refers to testing to detect somatic mutations in the tumour cells. The genetic profile of a tumour provides insight into the manner in which to treat, risk of recurrence and progression. A tumour is not representative of the individual’s genetics and even the presence of a germline mutation.

Summary of somatic mutations: sporadic cancer

Impact gene function in tumour cells

Genes: Tumour suppressor genes and related genes

Genetic test: Identify mutation in genes tested 

Reason for testing: Diagnosis of cancer 

Risk profile: Used for treatment, not for risk assessment

Inheritance: None

Prevalence: Specific to the cancer diagnosis

Guidelines: Cancer treatment, management and risk profiling. Not preventative. 

Example: OncotypeDx

Megan Scott is a genetic counsellor and obtained her PhD in 2021. Having worked in public and private genetic counselling clinics, she has consulted with individuals and families from many walks of life. She believes in a holistic approach to care and is passionate about making genetic information relevant and accessible.


Megan Scott is a genetic counsellor and obtained her PhD in 2021. Having worked in public and private genetic counselling clinics, she has consulted with individuals and families from many walks of life. She believes in a holistic approach to care and is passionate about making genetic information relevant and accessible. 

Header image by Adocbe Stock