genetic – The Tempest

On average, an estimated 15.2% of new cancer cases in the United States are women who have been diagnosed with breast cancer. That means that 1 in 8 women in the United States will develop breast cancer at some point in their lifetime.

These statistics are indicative of families, touched eternally by a cancer that is more than just a disease – it is linear. Breast cancer often weaves a thread, mangled in fate and fear, through mothers, daughters, and sisters alike. The survivors among them are the superheroes of nearly every generation of women, powering through all of the anxiety, body disfiguring surgeries or treatments, and impromptu decision-making associated with the onset of such an illness. They take this disease and nip it in the bud, almost passively, acknowledging the unforgiving weight that will forever be weighing down their bodies and minds.

In some cases, before these women can even think about what comes next, they are sewed up, stripped, and shaved. Left without any sensation in their breast area after a mastectomy, and feeling less and less whole with every visit to the oncologist. It is hard for most women to even feel at home in their bodies anymore.

In February of 2017, my mother sat in a bleak and claustrophobic doctor’s office for her regular mammogram visit and heard the dreadful words that every woman lives in fear of, “I think we’re going to need to take a second exam. There may be cancer.”

There was.

She has told me that she spent most of her life, 38 years to be exact, in terror of what was surely to come. When my mother was 17 years old, the same age that I had been when she was diagnosed, her mother passed away after a long and debilitating battle with breast cancer. Afterward, this disease became a constant threat. So, in some ways, her diagnosis was more of a relief than anything else.

For me, however, it was excruciating. I had a hard time fathoming the enormity of it. Often, I would find myself drenched in hot and burning tears, unable to put into words what I was feeling. I was incoherent and unable to be comforted. I really hated it when people tried to comfort me, too—it felt condescending. I didn’t want to need them.

But, at the same time, I wasn’t even close to being the strong person that I presented to the world. I was falling hard—and fast. Most days, I would go to school or hang out with my friends, but the entire time I felt as if there were a million knives stabbing my chest at any given moment, and I couldn’t help it. Sometimes, I even liked feeling the pain. If my mom had to suffer, then, I thought, so did I.

Years later I’m able to articulate my thoughts a little more clearly. I was terrified, desperate, and I didn’t know where to turn. So much was happening all the time and I was grieving my old self. That is, the self that hadn’t yet felt such complete and sunken remorse. There was this urgency to do everything right. In a situation like that, there’s no room for mistakes and I was incredibly nervous that I would mess up. Or maybe I was nervous that something would mess me up. Either way, I changed a lot that year.

Unfortunately, our story is not an uncommon one.

A woman’s chance of developing breast cancer increases if her mother, sister, or daughter has been diagnosed. In addition, women who carry the BRCA1 and BRCA2 gene are at an increased risk of breast cancer than women who do not carry the gene.

My mom is thankfully, and gracefully, in remission today. Her fight seemed, on the outside, to be continuous and suffocating. But, she is a survivor, bold and vivacious, in all of her glory. She has the scars and the strength to prove it, too.

I am well aware that my risk of this disease is high. But, I am also confident that this does not mean that it is a death sentence. Regardless of being only 21 years old, I am diligent in conducting breast exams on myself at least once a month in an attempt to detect any early warning signs of breast cancer. What I search for is any abnormal lumps or changes in the breast tissue/skin.

The good news is that with advancing technologies the survival rate of people diagnosed with breast cancer is steadily increasing, even though the number of people getting sick remains stagnant.

Any cancer diagnosis is terrifying, but breast cancer for me feels like a self-fulfilling prophecy. I won’t be able to stop being overwhelmed by this sharp and unrelenting nervousness until it is completely out of my system. And we all know that there is only one way for that to happen.

For now, I am trying to focus on what I am able to control. Breast cancer is certainly not one of those things. But, I am in control of my mindset. While it is important for me not to let my guard down, at some point I have to just let go and let it be. I trust that fate will run its course.

I come from a long legacy of confident and courageous women, all beautiful and bountiful in their own right. So, it would be a disservice if I did not take their wisdom and hold onto it tightly. I mean, I watched while my own mother boldly stared her fears directly in the face. She never skipped a beat, not even for a second. Her resilience against a disease that is otherwise overbearing is nothing short of inspiring and I am so proud of her. Because of her, I am starting to think that maybe I can handle it too, that maybe I can be as brave as her, when and if the day comes.

I am not alone in my fear, although it may seem like it sometimes. I am one of millions living and feeling these same anxieties at full volume, so I must not let it overcome me. Instead, I have to remind myself to be introspective and to keep moving forward.

Nuclear DNA, or DNA that’s found in the nucleus, is probably the only type you learned about in high school bio. It carries all of an organism’s genetic information, which is used for proper growth, development, functioning, and reproduction. We get a set of DNA from each of our parents: one set from mom and one set from dad. In this Ask A Scientist piece, we delve into research on our third set of DNA: mitochondrial DNA.

Recently, there was news of the first baby born with DNA from three parents. The mother lost her first two babies to Leigh syndrome, which is associated with mutations in mitochondrial DNA. In attempt to circumvent this, doctors removed the nucleus from one of the mother’s eggs, placed it in a donor mother’s egg (after removing the donor egg’s nucleus), and fertilized this egg with the father’s sperm. The successful transplant led to the world’s first baby with DNA from three parents: mom and dad’s nuclear DNA and a donor’s mitochondrial DNA.

What is mitochondrial DNA?

Eukaryotic cells (which we are made of) contain a nucleus and other organelles. Organelles are “little organs” in the cell that carry out specific functions. Mitochondria, one of these organelles, generate energy for the cell in the form of ATP. This is why know it as the “powerhouse of the cell.” However, mitochondria are unique organelles because they have their own genetic material — independent to that in the nucleus!

Mitochondrial DNA (mtDNA) is different from nuclear DNA in a lot of ways. mtDNA is generally circular, while nuclear DNA is linear. Nuclear DNA has 3.3 billion DNA base pairs (the building blocks of DNA) – the mitochondrial genome is only made up of ~ 16,569 base pairs and only encodes for 37 genes. You might remember that there’s only one nucleus in a cell, where the DNA is tightly packed into chromosomes. We have two copies of each chromosome (46 chromosomes total). However, a single cell can have multiple mitochondrion and each of them has dozens of copies of the mitochondrial genome. Plus, mtDNA isn’t in the nucleus.

Why do we have mtDNA?

Given the shape of mtDNA and its independence from nuclear DNA, it’s possible that mitochondria came from bacteria. This theory claims that over a billion years ago, mitochondria were actually small aerobic (oxygen related) bacteria that were engulfed by a larger cell. Instead of digesting the small cell, the big and small cells developed a relationship. Perhaps that first big cell benefited from the smaller cell’s ability to use oxygen to produce energy! This theory originated from professor Lynn Margulis in the mid-1900s.

Thank your mother for your mtDNA!

Interestingly, unlike nuclear DNA, which comes from both your mother and father, only maternal mtDNA is passed down (maternal inheritance). Since this is unique to the maternal lineage, scientists think that they can trace human lineage through mtDNA inheritance. This might help us identify one ancient woman who is the most common female ancestor of all modern people. She is aptly named “Mitochondrial Eve” (the male equivalent is the “Y-chromosomal Adam”).

By C. Rottensteiner - TiGen, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=18624647 — By C. Rottensteiner – TiGen, CC BY-SA 3.0

Even though mtDNA is passed down by maternal inheritance, males still have it. We know paternal mtDNA gets eliminated but nobody knows why. Excitingly, earlier this year a group of scientists found a potential explanation. They observed that in C. elegans (a type of roundworm), paternal mitochondria are eliminated when the sperm and egg fuse. If this process was disturbed, embryo survival rates decreased. This is the first time a study showed experimental evidence to suggest that maintaining paternal mtDNA may be harmful.

mtDNA and biomedical research

Because of the number of mtDNA, there’s a much higher mutation rate in mitochondrial DNA. A mutation is a change in DNA sequence and is not necessarily always bad. However, when a mutation occurs in an important gene and alters the ability of the gene to function normally, it can contribute to genetic diseases. These mutations can occur spontaneously, due to errors in DNA replication and repair, or as a result of exposure to chemicals.

Since offspring inherit mom’s mitochondrial DNA, fathers with mitochondrial diseases aren’t at risk to pass on the disorder to offspring. However, since a single cell contains many mitochondria, each with multiple copies of mtDNA, symptoms of mitochondrial diseases can vary. Given that the role of mitochondria is to produce power for the cell, mitochondrial DNA diseases often affect tissues requiring lots of energy like the heart, brain, and muscles. Just last month, a group from Cornell University published a study suggesting a link between mtDNA and some forms of autism spectrum disorder. Right now, treatment options for mitochondrial diseases are limited but as the understanding of mtDNA and its effect on diseases grow, so does our ability to target and come up with potential treatments.