BRCA is a gene that repairs damaged DNA. Everyone inherits two, one from each parent.
Like all genes, BRCA can become mutated, altered in such a way that its function is impaired. Even a mutated BRCA gene can, and will, be passed down to subsequent generations. BRCA mutations occur in 1% of Ashkenazi Jews, are more commonly seen in hispanic than white women, and are more frequently associated with triple-negative breast cancer.
Two BRCA mutations have been identified that increase a woman's lifetime risk for breast cancer, BRCA1 and BRCA2. On average, the increased risk ranges from 50-85% depending on which mutation is inherited and how other factors, such as child-bearing and exogenous hormones, influence onset of the disease. BRCA mutations can be inherited from either parent. But here's where things get really interesting: if a woman inherits the BRCA mutation from her father, she tends to get breast cancer at an earlier age than if she inherits it from her mother. This is true not only for breast cancer but for other inherited diseases.
This phenomenon is called the parent-of-origin effect or, more precisely, genetic imprinting. Approximately 1% of all genes are affected in this manner. Since the only genetic difference between men and women is the presence of the Y chromosome (in males and its absence in females), the immediate question becomes, what is the Y chromosome doing, either directly or indirectly, to increase the potency of inherited genetic mutations?
Keep in mind, the Y chromosome has only one mission, but many functions: to transform the body from female (its natural state) to male and, in so doing, give its genes the chance to propagate onto the next generation.
The Y chromosome is a lone wolf, lacking another Y chromosome with which to pair. You recall from Biology 101, all female eggs contain X chromosomes, so the Y can never a Y compliment but must, instead, attach to an X chromosome for form an XY pair. When it does, the result is male.
But for all its swagger, the Y chromosome is only a tenth the size of the X chromosome - a mere 80 genes compared to the 1000 genes found on the X. It used to have more, leading scientists to wonder what will happen if someday they all disappear. (Or, as my friend, Charlene, says, "If they can put a man on the moon, why can't they put them all there?") Never fear, the Y chromosome has no intention of falling off the genetic map. The Y chromosome, like the middle class, has adapted to reduced circumstances. It preserves its genes by using a method common to (dare I say, other) viruses. The Y chromosome makes palindromic copies of its few remaining genes and sequesters them elsewhere in the DNA, in the manner of a counterfeiter storing a few freshly minted bills in a safe in the wall behind a painting.
It's hard to know what to make of the Y chromosome's viral-like impact on other genes, and intriguing to speculate about what the Y does to other genes that accelerates the onset of inherited disease.
Science gives us facts. Connecting them gives us an explanation and, if we're lucky and right about our explanation, it gives us knowledge. But beyond facts and knowledge, there is a vast space, a seemingly infinite, daunting distance to be covered before we get to truth, if we ever do. Seeking truth, though a worthy goal, is like looking for land after a wild ride at sea. You drop anchor, wade to shore and notice that the land is not firmly fixed but ever shifting with every wave that comes from behind.
After awhile you realize it's all connected, sea and land and sea again, but how?
For more information on BRCA mutations, see this You Tube video: www.youtube.com/watch?v=-GwdZIqJf8g]
I. Shapira, Does maternal or paternal inheritance of BRCA mutation affect the age of cancer diagnosis? ASCO meeting, JUNE 2011.