How cancer starts

My recent genetic testing has rejuvenated my wondering about how cancer starts. I'm not a biologist, but I am a physicist and it's natural for me to try understanding the behavior (and misbehavior) of our bodies and to hypothesize about what mechanism has caused my and other cancers.

First, I'm amazed that the human body works at all. It's an enormously complex machine that actually manages to keep itself alive rather well. It can accept a huge variety of food to maintain its structure and chemical balance. It takes all sorts of abuse and repairs damage to itself for years and years. Mechanically it is far more durable than mankind's best automobiles and airplanes. Computationally it performs tasks easily that sixty plus years of exponential growth in electronic computing has barely touched.

This is all accomplished through interacting chemical systems refined over millions of years of evolution. Our bodies are full of countless tiny chemical reactions tuned by feedback mechanisms to keep the whole system functional. There are systems to detect damage, repair it by regrowing lost cells, and stop when the repair is complete.

If we break a bone then a torrent of cells activates to clean up the mess and fill in the gap. Putting more load on our bones and muscles drives them to strengthen. Spending time in bed or as an astronaut in zero gravity spurs our bodies to save energy by diminishing our bones and muscles.

All of these chemical systems repair not only damage to the body as a whole but also microscopic damage to the systems themselves. We are continually bombarded by solar radiation, chemical poisons, mechanical wear, and the gradual disintegration of molecules over time due to the simple vibrations each atom makes a trillion times a second.

Because of all the interactions and redundancy built into us by the driving force of evolution, it takes many simultaneous failures to lead to death of our whole body. It's similar to how accidents work on a larger scale. A traffic fatality requires several things to go wrong: at least one driver disobeys traffic laws or becomes confused by a poorly designed intersection, the other driver doesn't notice the hazard in time, the brakes slip on rain-soaked pavement, the angle of collision bypasses the crumple zones built into the cars, the seat belts and air bags are unused or ineffective, the injuries go beyond what the passengers bodies can repair themselves, and the paramedics are unable to provide life-saving aid in time.

It's rare that a single mistake — taking one's eyes off the road to dial a cell phone or following the car ahead too closely — is enough to result in a fatality. Our bodies have many more systems to catch errors before they kill us. Faced with the danger of spoiled food we can save ourselves by seeing the discoloration, smelling the foul odors, gagging and spitting at the disgusting taste, vomiting, or neutralizing the ingested toxins through the chemical response of our digestive and immune systems.

Cancer is one way our bodies can fail, and it's particularly cruel since it starts as a way by which our bodies succeed: growth and repair. A cancer originates when a cell suffers damage to its genetic code and forgets to stop growing when its task is complete. But our cells have ways to detect genetic changes, so the change won't take effect unless the error correction system fails first. And our bodies already deal with misbehaving cells all the time by isolating and killing them. So there must also be a failure in recognizing the bad cell and stopping its rampage. Cancerous cells have the advantage that they are closely related to our healthy cells so it's harder for the immune system to recognize them as dangerous.

I used to wonder why cancer wasn't far more common. Ultraviolet light shreds our cells and mutates our DNA, but most of us don't develop skin cancer. Some people smoke for decades and fill their bodies with carcinogenic toxins but never get lung cancer. Now I realize that it takes multiple simultaneous failures for cancer to take hold.

A genetic mutation caused by the environment has a chance to be repaired. Or it might occur in a part of our DNA that's not critical — a skin cell changes its pigmentation. Or it could be immediately lethal to the cell and never spread. Or the cell could be recognized and killed by other cells. Or it could grow unrestrained but too slowly to affect overall health.

Environmental damage to our bodies is cumulative because it damages some part of our safety mechanism and makes it more likely that the next bit of damage will go uncorrected. Some of us are born with hereditary changes that didn't happen to have ill effects in our ancestors or that were beneficial under different circumstances.

This explains why it can be hard to determine which substances in modern life contribute to cancer. Maybe a certain artificial color doesn't cause cancer alone but it lowers the bar for the next toxin. Or it depresses one safety mechanism and becomes dangerous when combined with some other factor. Cigarette smoke must be very, very bad that it can so clearly be shown to be dangerous. The impact of the flood of new chemicals in our environment, after our ancestors have adapted though millions of years of savage evolution in a different environment, will be hard to sort out.

Genetic mutant

I went to Baltimore today to get genetic test results from my doctors at Johns Hopkins. The results were somewhat inconclusive. It seems that my case is unusual even among unusual cases of cancer.

The first test was for microsatellite instability. They examined the DNA of my cancer cells to check for excessive repeats in the base sequences. Two of the five markers they examined were unstable, qualifying the specimen as having high microsatellite instability (MSI-H). That result is suggestive of a hereditary factor. It's also correlated with a better prognosis: "Colorectal carcinomas with no indication of microsatellite instability (MSS) have been associated with worse stage-specific survival after surgical and adjuvant therapies than those with MSI-H."

The second test looked at the expression of protein production in the cancer cells. With high microsatellite instability they expect certain proteins to be missing from those cells. However, my results showed that all of the proteins they checked were present. It's possible that the proteins were present but nonfunctional due to mutations or misfolding.

Since these first two tests suggest a hereditary cause but are inconclusive themselves, the next step is to examine certain genes from my normal tissue. There are four genes known to be involved in hereditary colorectal cancers and defects in two of those genes produce 90% of the cases. So they will start by checking those first two genes.

I'm not sure whether being diagnosed with hereditary colorectal cancer would be good news or bad. The average prognosis is better, but it also means a greater chance of recurrence and a greater risk for my relatives. The information is also interesting to the doctors at Johns Hopkins academically and might help direct treatment some day in the future.

Reevaluation

After a year on Xeloda plus Avastin, my CEA has reached the normal range and stayed there for a month. I took a week off from chemotherapy to share a vacation with my family (mother, three sisters, two brothers-in-law, one niece, three nephews, and my girlfriend) in Florida.

By the end of the week I felt something surprising: normalcy. My energy level is good, my appetite is solid, my skin condition is closer to normal. My previously tumor-ravaged hip joint didn't give me any trouble in miles of walking per day. My mental capacities are slowly improving enough so that I started a fresh batch of computer simulations for work, something I haven't done since declaring my cancer returned in June 2006. I don't feel like I have cancer anymore.

We are continuing with chemotherapy and that alone will be enough to make me feel sick for the coming months. But we have quietly reached the milestone where it's worthwhile to reevaluate the state of my body and look for a basis of hope that good health can last beyond a few weeks or months.

There will be a flood of information coming and it will keep me busy running medical errands. I will receive genetic test results from Johns Hopkins University next week. The following day I will get a radioactive injection for a full body bone scan. I will return to the National Institutes of Health for CT and PET scans. And we'll continue to watch my CEA and see whether it rebounds or stays low.

I'm starting to think about what to do with myself if we declare my cancer in remission and stop treatment. The first time I reached remission we thought I might be cured and treated it as a cause for celebration. This time I'm reluctant to hope for being cured. But for all the unexpected tragedies in life, isn't it possible to sometimes find an unexpected miracle?

Cancer quantified

Since starting treatment more than three years ago, our main measurement of its effectiveness has been the level of carcinoembryonic antigen (CEA) in my blood. CEA is a protein involved in cell adhesion that is normally present in a developing fetus but not in an adult. A plot of CEA versus time shows the history of my cancer's ebb and flow.


A normal CEA level is below 2.5 ng/mL. Higher levels can be produced by gastrointestinal cancers, and levels above 20 ng/mL are associated with metastatic tumors. Note that the vertical scale is logarithmic, not linear, so each major tick is ten times higher than the one below. My CEA was at 23 when diagnosed in August 2004.

Colectomy (removal of the lower colon) and FOLFOX chemotherapy reduced my CEA to normal. A laparoscopic examination showed that I still had many small tumors remaining, so in May 2005 surgeons removed my peritoneum (a membrane covering organs in the abdomen) and diseased parts of many other organs. Then they applied direct, heated chemotherapy to kill any remaining cancer cells.

The surgery seemed successful, but in early 2006 my CEA shot back up to worrying levels. CAT scans and PET scans confirmed that tumors were growing in several spots, particularly around the pelvis. We started chemotherapy with Erbitux and Camptosar, but the cancer kept growing.

In November 2006 we tried the oral chemotherapy Xeloda plus Avastin. The cancer responded well, and my CEA has dropped from a high of 160 ng/mL down to normal. We are continuing chemotherapy since a normal CEA does not necessarily mean that all the cancer is gone. I'll get scans again in a few weeks to see if those have cleared.

Interruptions

A new school year is starting, and I happen to be in Michigan as September cools toward October. This is where I spent most of my first days of school, from kindergarten to college and graduate school.

I went to a college football game yesterday, the first one I've attended in person since finishing my last degree in 2003. Being back on campus made me think more intensely about the environment of school: the things I enjoyed, the things I miss, and the things I'm happy to be done with.

I became ill during my graduate schooling, and in retrospect my symptoms were probably caused by my cancer and went misdiagnosed for four years. The illness did slow me down sometimes and stunt my activities, but mostly I chalked it up to aging and a delicate constitution and continued about my business. The cancer was not diagnosed until the symptoms became more intense a few months after leaving school.

I wonder what I would have done if the diagnosis was made while I was still a student. Would I stay enrolled? Skip a semester? Leave entirely? I would probably have wanted to stay, but after experiencing surgery and chemotherapy I can't imagine that it would be possible to keep up while going through those.

And if I took a break when would I know to go back? In reality, doctors never say "Congratulations, we've removed the cancer and you're cured!". The results always feel very fragile — the drugs unpredictably knock the cancer down to immeasurable levels and you hope that it doesn't grow back, at least for a while. The chemotherapy may take months or years, and you have no idea how long a break will last when it comes.

Can you commit to years of schooling when you doubt that you can get through uninterrupted? What do you do if a final project is coming due and you start to feel something funny in your body? Do you push through and see the doctor later, or do you drop the schoolwork to go for consultations, lab tests, and scans? What happens to your social network, coursework, and housing if you get pulled away in the middle of a semester and can't return for a year? Does it even make sense to pursue education when you have a fatal disease?

I've met other young cancer survivors and I feel sad for those who were struck in college or graduate school and had to drop out. Myself, I answered many of those questions consciously before I knew what was making me sick and decided that finishing my doctorate was an invaluable goal. Particularly the final year of school I completed through stubborn determination and health be damned.

I'm realizing now that those issues don't stop with graduation. The intense, planned, compulsory institution of education is past (unless I go back as a teacher, which I'd like). But the freeform development of postgraduate adulthood is still enormously impacted by cancer.

Right now I am on a biweekly chemotherapy cycle. I get an infusion on the first day, take poisonous pills for seven days, and then recover for seven days. Out of that I usually feel pretty good for the last four days of recovery, bad for the last four days of poison, and so-so on the other six. My mental capacity fluctuates from good days to bad. I lose memory, quickness, creativity, and ambition on the low days. I imagine that if I were in school I would forget and disregard my classes on one week and realize how far behind I've fallen the next.

I'm trying to figure out how to plan and evaluate events with the knowledge of what's going on in my body. What in the past three years has been a true reflection of my character and what is a temporary handicap of my illness? It's hard to know in the midst of this great disruption.

The face of cancer - 9 months

It has been three years since my diagnosis with Stage IV colon cancer. Three years since my first surgery and three years since my first chemotherapy. And it has been nine months since I began taking daily photographs to chronicle the changes in my appearance.

Three months ago I posted my first Face of Cancer video, and now I have an update. It is available in high resolution or as a low resolution stream from YouTube.



I am still in my third round of chemotherapy, nearing a year on that treatment. I'm feeling pretty well, walking normally, traveling more, and being productive. It's hard to believe that in January I was bald, had a broken pelvis, and was about to go through several months of pain and bleeding due to radiation treatment.

In my eyes the video shows me feeling better as the cancer and treatment effects subside. I hope to continue in that direction and have another, even healthier update at the one year mark.

Infertility

Three years ago tomorrow I was diagnosed with colon cancer. Five days later I had surgery to remove the two-inch tumor that a colonoscopy had found just above my rectum. I was 31 years old, fresh out of graduate school, and dating but unattached.

On the day of the surgery I was still stunned from the diagnosis. I had high hopes that the cancer was localized and could be removed without permanent damage that would curtail a long and ordinary life. But as I woke from sedation after the surgery I learned that the news was much worse. The cancer had spread and was probably incurable. There were unremovable tumors throughout my pelvis and abdomen. To protect the remaining two-thirds of my colon, the surgeon diverted it to an opening in my abdominal wall rather than reattaching it to my rectum. My bowel movements would now exit through that hole into a plastic bag that I must wear, and without a sphincter I would be unable to control when gas and stool would make its exit.

Still, I didn't feel like I was dying. I hoped that chemotherapy or further surgery would yet buy me months and years of good health. I wanted to continue with my life on the path I had been taking before: work, education, recreation, and relationships. I was still young, ambitious, curious, and horny. As I learned about the changes in my body I wondered, "Can I still walk and work and travel like a normal person? Will anybody find me attractive again? And if they do, can I still function sexually?"

That's a big worry for a young man. It might be true that 20% of a man's waking hours are spent thinking about sex. Probably more if you count the time a man spends trying to make himself more attractive in the hopes of winning a mate (grooming, exercising, earning money, improving education, gaining power). It's far from the only important aspect of a relationship, but it would be a big blow to my identity if removed completely.

The worry was fueled by the fact that during my three days in the hospital I never had an erection. Any female reading this will probably laugh, but that's the longest that organ had gone quiet since age 12. A day or two after I got home from the hospital, while I was still in pain from surgery and in shock from everything, my curiosity drove me to test it manually. I was relieved to discover that I could still get an erection and achieve orgasm but, strangely, there was no ejaculate.

I thought it might be a temporary change. After all, my body was full of painkillers and that general area had received some startling rearrangement with a scalpel. Maybe it had reverted to how it worked when I was 12 and would regain full function after a few weeks' recovery.

I didn't ask my surgeon about this symptom. How could I? He was telling me how poor my prognosis was and that in the best case scenario I would need months of chemotherapy, a heroic surgery, and still be left with a brief and uncomfortable life. Should I say, "Yeah that's all fine, and I know that I'm unmarried, but what really worries me is that I can't ejaculate?"

Three years later the situation remains. I have a girlfriend now and appreciate that most things work. And it is convenient to have less mess and no need for extra birth control. But it does make orgasms less intense, and as a man it makes me feel less potent and powerful. And it means I won't ever by having kids, at least not without major medical intervention.

I'm not sure I wanted kids anyway. And I don't think it's responsible for me to try when it still appears unlikely that I would live long enough to raise them. I see my peers becoming parents and it looks like an enormous burden. I know that it's rewarding, but maybe I'm better suited to be a teacher and an uncle than to be a father myself.