CapeRay blog

A Tale of a Faulty Gene

In 1961 Mary-Claire King was just fifteen when she watched her best friend die of a kidney tumour. She recalls, “Her death was devastating. It seemed so unfair. It wasn’t a conscious decision, but I said to myself, something needs to be done. It’s the little pebbles that make a path.” King’s youthful determination led to a spectacular breakthrough thirty years later when she was a distinguished professor of genetics at the University of California at Berkeley.

In a seminal paper, published in Science in 1990, King and her colleagues provided evidence for the existence of the first gene for hereditary breast cancer. They showed that chromosome 17 was the locale of a gene — later named BRCA, short for BReast CAncer — for inherited susceptibility in families with early-onset disease. King’s research transformed the field, enabling the gene to be cloned and the development of a simple diagnostic test.

Earlier this week the actress Angelina Jolie wrote an op-ed piece in The New York Times, revealing that she had undergone a double mastectomy earlier this year despite the absence of breast cancer. Her mother had died of ovarian cancer at age 56 and Jolie, having been diagnosed with the faulty BRCA1 gene, decided on prophylactic surgery. Her doctors estimated she had an 87 percent risk of breast cancer and a 50 percent risk of ovarian cancer. “Once I knew that this was my reality,” she said, “I decided to be proactive and to minimize the risk as much as I could.”

Jolie described in considerable detail the surgical procedures, including the subsequent reconstruction of her breasts with implants, commenting that her choice did not in any way diminish her femininity. She stated that her chances of developing breast cancer had fallen to less than 5 percent, and concluded: “Life comes with many challenges. The ones that should not scare us are the ones we can take on and take control of.”

Perhaps unsurprisingly, news of Jolie’s decision generated considerable debate. Myriad Genetics, the company that developed the diagnostic test and is now facing a legal challenge to its monopoly in the US Supreme Court, saw its stock rise after the announcement. A recent paper in the Journal of the American Medical Association has shown that prophylactic mastectomy does indeed reduce the risk significantly. It’s intriguing to think how one woman’s discovery almost a quarter of a century ago led to another woman’s decision to take control of her own destiny.

One Response to “A Tale of a Faulty Gene”

1. David Dent

   
   May 17, 2013 at 5:32 pm

   There have been two widely held criticisms: firstly of Jolie’s drastic choice, and secondly publishing her own account in the New York Times. With regard to the first, mastectomy is the strongest preventive act we know, far more effective than endocrine prophylaxis (weak), and super-surveillance (closing the stable door…) With regard to going public about it all, the illnesses of the famous, like heads of state, actors and actresses, popes, and sports people, are in the public domain. This was an accurate and honest account of the events. She has added to breast awareness and advocacy, and has bravely made an important contribution to the management of breast cancer.
   An unfortunate aspect was the blatant advertising of the Pink Lotus Breast Centre http://www.pinklotusbreastcenter.com/ , hitherto completely unknown for its contributions to the understanding and management of breast cancer. The commercialization of breast cancer, if you will.

   Reply

Can Exercise Lower Breast Cancer Risk?

Yesterday the Cancer Council in Australia announced that the country was gaining the upper hand in the war against cancer, with 60,000 lives saved over a two-decade period. They attributed their success to three factors: prevention, screening and treatment. One of the issues identified was obesity — a major risk factor for bowel and breast cancer — and the Council suggested that weight reduction programmes had contributed to the improved statistics. This begs the question: can exercise lower breast cancer risk?

In a study published last year in the Journal of Clinical Oncology, researchers from Seattle showed that women who exercised and dieted to lose a moderate amount of weight also experienced a reduction in their oestrogen levels and other hormones associated with increased breast cancer risk. They studied 439 overweight and post-menopausal women aged 50 to 75 who were sedentary, and divided them into four groups: (1) a diet group who cut out sugary beverages and desserts while increasing fruit, vegetables and fibre; (2) an exercise group who did five 45-minute aerobics classes per week; (3) a group who both dieted and engaged in brisk walking; and (4) a control group who made no change to their diet or exercise habits.

At the completion of the 12-month study, groups 1 and 3 saw the greatest benefit, having dropped an average 10% of their starting weight, and also experienced a statistically significant reduction in their oestrogen levels and other hormones. Anne McTiernan and her co-authors estimated that a 5% weight loss may reduce a woman’s breast cancer risk by 22%. Interestingly, women in group 2 who exercised but failed to lose weight did not lower their hormone levels.

Another study, just published in Cancer Epidemiology, Biomarkers & Prevention, by researchers from the University of Minnesota reported that women who exercised five times a week for 16 weeks demonstrated changes in their oestrogen metabolism. “Ours is the first study to show that aerobic exercise influences the way our bodies break down oestrogens to produce more of the ‘good’ metabolites that lower breast cancer risk,” said lead author, Mindy Kurzer.

Can the findings from these two studies be reconciled? Perhaps they can. Although exercise may not lower oestrogen levels per se, it does appear to change the break down of oestrogen and modify the metabolites that, in turn, reduce the risk of breast cancer. This is good news for women who are willing to make the effort and exercise.

May 10, 2013   2 Comments

A Miniature X-Ray Source

Sixty years ago, three Soviet scientists published a paper, in Russian, entitled “Study of electronic emission during the stripping of a layer of high polymer from glass in a vacuum.” They demonstrated that a process called triboluminescence — where relative motion between two contacting surfaces produces visible light — converts mechanical energy into electromagnetic radiation, including X-rays. As often happens in the history of science, this phenomenon lay dormant for over fifty years until 2008 when a group of physicists from the University of California at Los Angeles (UCLA) published an article in Nature entitled “Correlation between nanosecond X-ray flashes and stick-slip friction in peeling tape.”

Like all good entrepreneurs, the researchers filed a provisional patent before publication and assigned the intellectual property to their employer. Three years ago one of the inventors, Carlos Camara, formed a company called Tribogenics to commercialise the metal-polymer technology which they licensed from UCLA. Their small powerful X-ray sources are scalable and can be configured as single point emitters or clustered into flat-panel arrays of X-ray pixels that can be individually addressed. Since the fragile glass tube and high voltages have been eliminated, these X-ray sources are apparently safe to use in any environment.

Tribogenics will be applying their X-Change sources to medical care, including therapy — such as low-cost radiation oncology — and diagnostics, where compact array-based imaging is envisaged. An intriguing image on the company’s website illustrates a mock-up of a portable X-ray machine, where a soldier lies in a field while a medic with a laptop computer studies an X-ray of the man’s lower spine.

So how does the technology work? According to the authors, “As the tape peels off, the sticky acrylic adhesive becomes positively charged and the polyethylene roll becomes negatively charged, so that electric fields build up to values that trigger discharges. At a reduced pressure, the discharges accelerate electrons to energies that generate Bremsstrahlung X-rays when they strike the positive side of the tape.” While there are experts like Ken Suslick at the University of Illinois who are skeptical that so much of the mechanical energy can be transformed into X-rays, Camara and his team at Tribogenics are pushing ahead regardless.

It’s an interesting thought that at some stage in the future, an experiment performed with an off-the-shelf roll of Scotch Tape mounted on ball bearings in a vacuum chamber could lead to a miniature X-ray source that will aid in the diagnosis of breast cancer.

May 3, 2013   3 Comments