Nature-nurture synergy: The inside battle against cancer

It’s not just what happens in the external world that fascinates us, but what happens within our bodies is just as, or more fascinating. How do we copy genes from our parents? What happens if they are not copied well? What role does environment play in exposing us to diseases like cancer? And how does our body battle to suppress tumours, every single day?

Ashok Venkitaraman, Director at the Cancer Science Institute of Singapore and Distinguished Professor of Medicine at the National University of Singapore, walks us through this interplay of genes, DNA, cells, and environment, and the tussle between oncogenic influences (promoting cancer) and tumour suppressive influences.

Delivering the Dr Reddy Memorial Lecture in Hyderabad, Venkitaraman says the risk of developing cancer is determined by a combination of factors, including genes inherited from our parents, the environment, diet, and lifestyle. Unravelling this ‘nature and nurture’ interplay is crucial in understanding cancer risk.

Individuals may inherit from their parents faulty copies of tumour suppressor genes such as BRCA1 or BRCA2, which normally prevent uncontrolled cell division and DNA damage. While inheriting one bad copy may not immediately cause cancer, it creates a predisposition, as the remaining good copy maintains its function.

A genetic predisposition (such as a faulty tumour suppressor gene) combined with environmental factors can contribute to a breakdown.

Dangerous synergy

Research demonstrates a specific mechanism of gene-environment synergy involving aldehydes. Exposure to aldehydes (found in alcohol metabolism, car exhaust, and cosmetics, and produced endogenously) can lead to the degradation of the BRCA2 protein.

Research also connects metabolic disorders like diabetes to increased cancer risk through similar mechanisms. In diabetes, elevated glucose levels lead to increased production of metabolic byproducts like methylglyoxal (an aldehyde).

Alterations in metabolism from diet and diseases generate reactive molecules that damage DNA and impair the function of key cancer-protective proteins. “Cancer starts in lesions that involve just tens or thousands of cells, but it grows from there to lesions that involve billions of cells. We know that at very early stages, cancer is potentially curable, not just treatable but potentially curable,” he points out.

Sadly, cancer is usually treated when it is advanced, he observes, “And even though we have known for over 30 years that early intervention in cancer can greatly improve clinical outcomes, less than 20 per cent of cancer research worldwide focuses on this really, really key issue.”

Cancer primarily affects people as they get older, he says, as “it incubates within us without causing any symptoms for a long, long time, often decades.” But a lot can be done to prevent cancer — “primary prevention… before it gets a foothold and before it progresses.”

He cites examples of how changes in behaviour or lifestyle, including diet, and avoiding exposure to toxins in the environment can help reduce the risk of cancer.

“We are beginning to see the advent of the use of drugs not to treat chronic diseases, but potentially to prevent chronic diseases like cancer,” he points out.

What puts us at risk to any disease, including cancer, he asks, before answering, “It’s our genes, which we inherit from our parents through generations. Coupled with our environment — what we expose ourselves to, what we eat, what we breathe. And together — nature and nurture — determine cancer risk.”

The DNA factor

“The information that makes us what we are is encoded in our DNA. Imagine DNA as a book — a book with many, many billions of letters written in chapters. Not all of these chapters are read in every cell in our body,” he explainsd.

“A cell in the liver may read certain chapters of this book, a cell in the eye may read other chapters — same book, different cells. And that is because the DNA encodes molecules like proteins, which make the cells what they are. And these cells come together to form organs, which make us what we are.”

What’s interesting about this book of life is that it is not static. Every time a cell divides, the book has to be copied, and it has to be copied perfectly, without any errors, or the progeny will be sick.

“But errors do occur, not just because this process is not perfect, but also because we’re exposed all the time to lesions in our DNA,” he says.

“If you stand outside in bright sunlight for an hour and then look at one square millimetre of your skin, the ultraviolet light will induce thousands of alterations in the DNA. Why don’t we all get cancer every day? It’s because there is a fantastic machinery within ourselves that repairs these lesions.”