For Shaw Prize winner Mary-Claire King, mapping genetic link to breast cancer just one of many challenges overcome
Groundbreaking researcher recalls scepticism in field as well as technological constraints in career marked by mathematical approach and inspired by father’s questions
Scepticism from fellow researchers and other challenges greeted American geneticist Mary-Claire King when she set out to establish a genetic link to breast cancer more than four decades ago.
King, 72, won this year’s Shaw Prize for life science and medicine for mapping the first breast cancer gene, BRCA1.
“The major challenge was that the technology at that time did not exist,” she said of her long road.
When King began her research in 1974, most in the field believed cancer was viral.
“It was caused by viruses. That’s true,” she added. “But not all cancers are caused by viruses, and some cancers as we now know are in part a consequence of inherited mutation.”
King persisted because a significant amount of statistical data generated around the world from the 1920s indicated that daughters of women who died of breast cancer were more likely to develop and die from the disease themselves.
The groundbreaking researcher, who earned her bachelor’s degree in mathematics from Carleton College in Minnesota before receiving her PhD in genetics from the University of California, Berkeley, used mathematics to see if there was a genetic model to test her hypothesis.
King studied more than 1,500 families in which multiple members were affected by breast cancer.
Using a mathematical approach, she predicted that clusters of cases could be best explained by the presence of a disease-linked gene in about 4 per cent of families.
She also predicted that among women carrying gene mutations, the risk of breast cancer was about 80 per cent by age 70 whereas the risk fell to 8 per cent among women without them.
But still there was scepticism about her mathematical model, so King set out to show the existence of a breast cancer gene by locating it using linkage analysis. In 1990, she mapped the gene to human chromosome 17.
Now the American Cancer Society professor in the departments of medicine and genome sciences at the University of Washington, King has a straightforward explanation for focusing on breast cancer: she described the disease as one of the easiest cancers to diagnose and a common cause of death.
In the absence of genomic tools for human genetic analysis, she explained “it was therefore necessary to develop the technology – that is, to sequence the genomic regions – to learn the sequence of BRCA1”.
King cited two major reasons her discovery was important.
“First, women can now learn, while they are still healthy, if they carry a mutation in BRCA1 or one of its sister genes, and if so, can take measures to prevent ovarian and breast cancer,” she said.
“Second, the discoveries of BRCA1 and BRCA2 enabled the development of chemotherapy targeted specifically to tumours.”
Under current international recommendations, women by age 40 or those who have finished having children should have their ovaries and Fallopian tubes removed to reduce the risks of ovarian and breast cancer.
King believed 15 per cent of breast cancer cases involving Chinese women were inherited, comparable to the numbers for their Western counterparts.
“Breast cancer is now increasing very rapidly in China and in Hong Kong,” she said. “This is not for genetic reasons. This is because the principal risk factors for breast cancer are now much more prevalent in China than they were in my generation.”
Improved nutrition means women are entering puberty at younger ages, while better education is tied to many postponing having children.
“The longer that period is between beginning to menstruate and having one’s first child, the higher the subsequent risk of breast cancer,” she said.
King also offered advice for encouraging young girls to study science and mathematics.
“Give young girls confidence in themselves. Schools and teachers are important, but fathers and mothers are extremely important for a girl to have confidence that she can do mathematics while she’s still very small.”
King recalled that when she was a girl, her father would pose maths questions to her about baseball while they watched games on television.
“Every game he would make up problems and he would teach me the answers and say, ‘That was very good. I will give you a harder problem’,” she said. “So I grew up always assuming that this was something that you did with your dad.”