Angelina Jolie’s recent announcement in a New York Times op-ed that she had a prophylactic double mastectomy due to her BRCA1/BRCA2 status, has ignited a lot of discussion about absolute versus relative factors influencing gene expression, and the appropriateness of her decision to undergo ‘preventive’ surgery. Much of the more controversial discourse centers on a broad definition of ‘epigenetic’ factors, and whether less invasive, alternative approaches may have been more suitable.

Factors beyond the control of the gene, known as epigenetic factors, do influence Cancer expression.

However, these are more likely to take the form of promotor and blocker sequences in the genome, turning on and off oncogenes, protein mediated developmental factors that influence gene expression, polygene expression of phenotypes, and ribosomal factors which influence assemblage of expressive proteins; all of which can profoundly influence the ultimate expression of a given gene.

I sincerely doubt the relevancy of such statements by ‘greenmedinfo’ (and others like it), that factors beyond the control of the gene are “largely determined by a combination of nutrition, psychospiritual states that feed back into our physiology, lifestyle factors, and environmental exposures, constitute as high as 95% of what determines any disease risk” – this is mere psycho-babble which tries to give more weight to environmental, mystic, and ‘nurture’ influences, than to intrinsic, coded, ‘natural’ influences. Most people cannot meditate their way through an Ebola, or Yersinea pestis epidemic, but good hygiene, hand washing, intrinsic avoidance of the causative agent manages quite nicely, as Nostradamus showed in the 14th century during his medical-doctor years in the south of France.

Yes, “the psychological trauma associated with being diagnosed with cancer can drive malignancy”, as can ANY stressor which reduces our immunological resistance, and may produce hormones and activator substances (which are a natural expression of our flight or fight response), which in turn create a phenotypic pathway to induce continued cancer growth; or in the case of the “recent NEJM study, lead up to a 26-fold increased risk of heart-related deaths in the seven days following diagnosis”, by further taxing an already overtaxed and likely diseased heart. But these are merely the mechanistic expressions of existing intrinsic phylogenetic traits.

As to Jolie :
12.0 percent of women (120 out of 1,000) in the general population will develop breast cancer sometime during their lives

60 percent of women (600 out of 1,000) who have inherited a harmful mutation in BRCA1 or BRCA2 will develop breast cancer. This is Five times more likely than a woman who does not have such a mutation.

1.4 percent of women (14 out of 1,000) will be diagnosed with ovarian cancer in their lifetime

15 to 40 percent of women (150–400 out of 1,000) who have a harmful BRCA1 or BRCA2 mutation will develop ovarian cancer.

Mutations in several other genes, including TP53, PTEN, STK11/LKB1, CDH1, CHEK2, ATM, MLH1, and MSH2, have been associated with hereditary breast and/or ovarian tumors – their presence or absence may enhance or delay development of breast and ovarian cancer in women with these BRCA1 or BRCA2 gene mutations.

Specific mutations in BRCA1 and BRCA2, increased frequencies of over all mutations, combinations of different mutations, and redundant mutations are all much more likely to cause cancer in individuals. First degree relatives with Breast or Ovarian Cancer, and the presence of these genes, are a strong marker for increased genetic likelihood and cancer risk in individuals. Prior cancers, at young ages, whether in oneself or a first degree relative are also predictive.

These incidences are also more common in certain populations such as Eastern European Ashkenazic Jews, and other ethnic and geographic groups around the world, like Norwegians, Dutch, and Icelandic peoples, and individual racial and ethnic groupings within the United States (the “Great Melting Pot”).

Depending on the combinations of these risk factors a given individual may have as much as an 85% (or greater), likelihood of developing Breast or Ovarian Cancer. These sorts of odds are profound, especially in terms of whether or not to consider undergoing prophylactic surgery, before developing the disease. Once the disease is present, the risks of attendant surgical & treatment complications, and death, increase enormously; especially if contrasted with the prophylactic surgery, which once undertaken (while still healthy), those subsequent risks then become negligible.

I would not presume to decide for anyone, whether or not to undergo surgery to prevent Breast, or Ovarian Cancer disease. However, if asked to counsel them, and having outlined a personal risk greater than 40% lifetime (more than 3 times the average), I would urge them to consider such a procedure seriously.