Democratising Cancer Prevention with Germline Testing

Threads of Sorrow, Seeds of Hope A hundred years ago, a seamstress, needle pricked with worry, stitched together a tale of familial tragedy to Dr. Aldred Scott Warthin. Cancer, a malevolent tailor, had snipped away generations of her family, leaving her in fear of her inevitable death. She did indeed get endometrial cancer and died of the very disease that she had dreaded. 

Dr. Warthin, a doctor with a nose for genetic mysteries, saw beyond the fabric of coincidence and made efforts to unravel this family’s history thread by thread, creating a macabre tapestry woven with tumours – colon, endometrium, ovary. These were not random stitches, it was a genetic blueprint, a code begging to be deciphered. 

Decades of research followed as more people tried to understand what tied the seamstress’s family to the dreadful threads of cancer, to characterise and record the history of her family – ‘Family G’. Then entered Dr. Henry T. Lynch, an oncologist who meticulously traced the threads of cancer through the family tree. 

In his  landmark 1971 paper ‘Cancer Family G Revisited’, Dr. Lynch details an insidious autosomal dominant trait being passed down from generation to generation, that of a ‘Cancer Family Syndrome’ better known today as Lynch Syndrome. As molecular biology advanced and helped unravel strands of human DNA, the culprit emerged – faulty genes involved in DNA mismatch repair that normally protect us from developing certain cancers. 

Family G, though stitched with sorrow, became a beacon of hope that transformed research into inherited cancers, demanding awareness, detection, and a future where genetic mistakes would not dictate human fate.

Back in the 1970s, when Dr. Mary-Claire King started researching breast cancer, the prevailing knowledge held that it was caused by a virus. While the theory was not entirely off the mark as some cancers are indeed caused by viruses, Dr. King held a different notion and a bit of a lone wolf idea. 

Seeing the alarming prevalence of the disease in certain families she couldn’t help but suspect a genetic force at play. This hunch of hers led her to the discovery of the region on the genome that eventually became known as BRCA1, the first gene linked to a higher risk of breast and ovarian cancer. 

In 2013, the actress Angelina Jolie made headlines when she shared her personal journey of undergoing a preventive double mastectomy after discovering that she carried a mutation in the BRCA1 gene which significantly increased her risk of developing breast and ovarian cancers. She had previously lost her grandmother, mother, and aunt to cancer. 

Jolie’s decision, echoing the whispers of Dr. King’s research, sparked public interest in genetic testing for hereditary cancers. The “Angelina Jolie effect” led to increased awareness, discussions about genetic counseling, and a higher number of individuals seeking genetic testing to assess their risk of developing certain cancers. It also contributed to a broader conversation about the role of genetics in healthcare decisions and the potential for personalised medicine based on an individual’s genetic profile.