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Inheritance of maladies and the gene fairy

2013; BioMed Central; Volume: 9; Issue: 3 Linguagem: Inglês

10.4103/0973-1482.119295

0973-1482

Rajiv Sarin,

Science, Research, and Medicine

If cancer is the emperor of all maladies, its inheritance establishes a dynasty of maladies, casting its shadow over generations. Even with the most conservative estimate of just 1% of all cancers being hereditary, worldwide over 150,000 families may be coming in its grip each year and the actual numbers could be much higher. There are major global disparities in terms of number of cases identified as hereditary and being offered genetic counseling, testing, and risk management. While Asia accounts for 60% of the world's population, barely 5% of the known BRCA carriers identified so far are Asians,[1] reflecting gross underreporting in this region. In order to share knowledge of and to bring benefits to such families in Asia, we have recently established the Asian BRCA consortium with members in 12 Asian countries. This consortium estimates that for the year 2012, of the approximately 350,000 new breast cancer cases in these Asian countries, over 50,000 would have benefited from genetic counseling and if appropriate, genetic testing. However, only 1500 women were offered genetic counseling and barely 500 underwent BRCA1/2 genetic testing, with Korea accounting for more than half. If that is the ground reality, how could a personal story of a BRCA1 mutation carrier grab headlines in newspapers and popular magazines worldwide, including Asia? Was it to do with the shock element of a glamorous Hollywood actress undergoing double mastectomy to prevent cancer due to BRCA1 gene mutation or due to the inherent courage, convictions, and contradictions in a very human story? The lay press, electronic, and social media extensively reported each word and move of Angelina Jolie and her husband Bradd Pitt and also speculated on the possible motives and beneficiaries of the cascading hype. Using the analogy of the Tooth Fairy, who leaves a gift under a child's pillow in exchange for their fallen tooth, Angelina can be called a Gene Fairy who wishes to do for a broken gene what a tooth fairy does for a broken tooth - weaving a gift of protection and making them forget the future uncertainty. The concept of a gene fairy would be good for weaving stories and perhaps counseling children with genetic diseases. Interestingly before earning the title of a Gene Fairy from the Journal of Cancer Research and Therapy (JCRT), this UN Goodwill ambassador has played tooth fairy giving $50 to her adopted son every time his tooth fell.[2] While the majority of women did see in her a gene fairy out to lead her people away from danger, the skeptics were not silent, especially in the social media and in the responses to stories about Angelina. The skeptics thought her personal medical decision to be a little odd, her declarations bordering on attention seeking behavior, and her health advisors as scaremongers out to benefit professionally and financially. With her BRCA1 story breaking out just before the lawsuit against the Myriad Genetics BRCA1 patent was to be decided, speculations were rife about the timing of her declaration. Many wondered if the large-hearted women had become an unsuspecting tool in the hands of a self-serving biomedical industry. Those matters have been laid to rest to some extent with Myriad Genetics losing the battle. Mary-Claire King, the discoverer of the BRCA1 gene, in a recent interview, shared how delighted she is with the Supreme Court ruling that makes it illegal to patent genes.[3] As this JCRT editorial is being written, the news about Angelina has shifted from her mastectomy to her taking charge of her personal and professional life with telling pictures of a hard-working and self-confident actor back on the Hollywood sets. How did the medical journals and academic establishment respond to one of the biggest cancer-related story in the lay press in recent times? Few professional opinions did appear in the print and electronic media but they were distorted or drowned in the sensation surrounding the story. A search of PubMed and Google Scholar reveals that academicians and professionals were reticent during this media frenzy and could not come up quickly with their own considered view in their own media, which is the world of medical journals and professional websites. Few leading journals like the British Medical Journal (BMJ), however, did come up with a timely piece,[14] again in admiration of the brave lady. Some like Eric Topol, editor-in-chief of Medscape, probably got carried away by the occassion while proclaiming her story to be “the epitome” of individualized medicine. The academic world hesitates to take a stand without verifiable facts of a given case, especially when the subject matter is controversial, less understood, and does not fit in to a classical evidence-based management paradigm. These tags would fit for not so common disease predisposing states with variable long-term health outcomes such as carriers of mutations in cancer gene with incomplete penetrance. In such scenarios, as exemplified by healthy young women with germline BRCA1/2 gene mutations, it is difficult to prove survival benefit or harm of preventive interventions through large adequately powered randomized trials with sufficiently long follow-up. In such situation can we rely on extrapolated findings and mathematic modeling on retrospective and prospective case series[5] and give sound guidance to the high-risk person? If not, could a dialogue between the high-risk person, their counselors and doctor within a broad medical, psychological, and philosophical framework guide their medical management? These are open-ended questions for which we are unlikely to get a clear answer in a timeframe that would be relevant to the concerned individual. William Hazlitt in his collection of essays Table-Talk describes “The most rationale cure after all for the inordinate fear of death is to set a just value on life.” It will be difficult for others to judge how an individual sets a just value for his or her life. In Asian societies, when faced with some complex medical decisions, many of our patients still expect that their doctors would literally hold their hand and sometimes decide on their behalf. This cultural dimension poses a challenge in providing nondirected genetic counseling. I must admit that in my clinical genetics practice for Indian BRCA mutation carriers, after taking into account various medical and psycho-social reasons, I strongly recommend prophylactic salpingo-oophorectomy and mention the option of preventive mastectomy only in passing. But I respect the decision and reasoning for preventive mastectomy by a lady who would have been a silent witness to her mother, grandmother and aunt losing their battle to this disease. I feel we should not be overtly judgmental and allow men and women like her who have experienced a medical condition in the family from very close and have their own unique perspective to set a just value to their life. But what about the harms from preventive interventions and how do we measure them beyond routine medical and surgical outcomes of infections and pain. Could our tools to measure and report the quality of life incorporate an individualized philosophical dimension to guide vulnerable person such as a gene mutation carrier in making a very personal and complex medical choice? Samuel Johnson, the 18 th century English writer and philosopher said “That kind of life is most happy which affords us the most opportunities of gaining our own esteem.” The gene fairy has let the genie out of the bottle and let us hope it will do more good than harm. Proponents of direct to home and do it yourself genomics should take note of the complexities surrounding genetic counseling, genetic testing, and medical choices exercised by those found with a gene mutation, as brought out by the case of Ms Jolie. In the curious mix of cancer, genes, family, and psyche - To each his own! Source of Support: Nil Conflict of Interest: No.