Angelina Jolie’s Mastectomy: How Genes Relate to the Metabolic Origin of Cancer

Angelina Jolie’s May 14th op-ed in the New York times about her recent preventative double mastectomy was touching, courageous, and informative.  Most remain unaware of genetic predispositions to cancer including the BRAC1 gene.  The fact is, inherited mutations that result in an increased predisposition to acquire cancer are rare.  Only 5 to 7 percent of all cancers can be attributed to inheriting faulty genes.  The vast majority of cancers arise spontaneously – being attributed to environmental insults like carcinogens, radiation, and viruses.

Women in general have a 12% lifetime risk of getting breast cancer.  Women with a defective BRAC1 gene have approximately five times that risk – or on average, a 60% chance of getting breast cancer in their lifetimes.

A genetic test using a blood test can usually detect genes like BRAC1. There are no guidelines for recommending the test, and the test can cost several thousand dollars but may often be covered by insurance companies if women have risk factors that justify it. Women may be at higher risk for having the BRAC1 mutation if they have close family members diagnosed with breast or ovarian cancer at an early age, as in the case of Angelina Jolie

In Angelina Jolie’s case, a preventative double mastectomy reduces her risk of breast cancer from 87% to less than 5%.

You are probable wondering; If inheriting defective genes like BRAC1 increases your chances of acquiring cancer – isn’t that evidence that cancer is a genetic disease and not a metabolic disease?


BRAC1 located in the mitochondria

While it is certainly true that inherited mutations in genes can predispose an individual to a greater cancer risk – it is also true that in almost all cases of inherited cancer risk, the defective genes manifest in damage to the mitochondria – the metabolic origin of the disease.The image to the left is of labeled BRAC1 protein, clearly showing it located within the mitochondria.  Experimental evidence also implicates BRAC1 as being integral in the biogenesis of mitochondria and therefore oxidative energy creation.  So one can easily conclude that a defective BRAC1 does not cause cancer by itself – but rather predisposes one for cancer because it inhibits the function of the mitochondria, and therefore the ability to generate energy through oxidative pathways.

In the vast majority of cancers – the cases that arise spontaneously – there is no initial genetic defect that precipitates the transformation of a normal cell into a cancerous cell.  Rather, spontaneous cancer originates from mitochondrial damage followed by the genomic instability that leads to genetic mutations – mutations that have nothing to do with the origin of the disease.


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