At the start it all seemed so innocent. My wife Nancy was doing sit-ups in the gym when she noticed a lump on the inside of her right leg.

It didn’t go away, and she was diagnosed with a tumour that had started for no good reason in her uterus and burned down into her groin.

You start looking for a reason — how can a cell minding its own business transmogrify into a monster growing within?

As a science journalist I found something sickly fascinating about the way a single cell can break from the pack and start multiplying, creating something alien.

Nancy had some known risk factors. She was 43 and we had no children — something we often argued about.

The less frequently a woman is pregnant, the more monthly menstrual cycles she endures.
With each period a jolt of oestrogen causes cells in the uterus and mammary glands in the breast to begin multiplying, duplicating their DNA, preparing for a child that may not come.

Each menstrual cycle is an opportunity for copying errors that might result in a rogue cell emerging.

Oestrogen (along with asbestos, benzene, gamma rays, and mustard gas) is on the list of known human carcinogens published by the U.S. government’s National Toxicology Program.

Women are now also exposed to more monthly doses of oestrogen because they are beginning to menstruate much earlier, possibly increasing breast cancer risk.

At the same time, women spend less of their fertile life pregnant or nursing. Lactation also appears to hold oestrogen in check.

The result is that a teenager today may have already experienced more menstrual cycles than her grandmother did during her entire life.

When Nancy’s cancer was discovered, batteries of tests were needed to discover its precise nature. We didn’t know for weeks where it started, only that it was shedding cancerous cells into her body.

Finally, we learned she had cancer of the uterus. That can be relatively good news if caught early. Nancy’s cancer had, however, advanced to a lymph node in her groin, which lowers the average survival rate to about 15 per cent.

But those are just averages. Nancy’s youth gave hope for a better than normal outcome. She was strong and could tolerate multiple rounds of sickening chemo and burning radiation.

First, however, would come the surgery: a hysterectomy and removal of suspect lymph nodes. This revealed a tumour that had eaten 3mm deep into her uterus lining and begun spreading into the upper end of her cervix.

From there, the cancer had manoeuvred down one of the ligaments which help to hold the uterus in place, occupying surrounding tissue, then heading for the right groin. There, it invaded the skin and jumped through the lymph system to nodes in her left groin.

After the operation, Nancy lay in the recovery room, barely awake. She smiled when she saw me and her brother, then lapsed, safe for the night, into unconsciousness.

Remembering all this now I am washed over by the sadness my wife had felt about not having children — a sadness she tried so many times to explain to me, to get me to feel in my own heart. Now childbearing was no longer an option, with me or anyone.

When the postsurgical report came back from the lab, the story became more complicated. The cancer in her uterus was weak. How could it have spread so quickly?

The answer seemed to lie in a polyp, a centimetre in size, that had also been cut from Nancy’s uterus.

What had marched with such determination down the ligament and into the groin was a very rare cancer called uterine papillary serous carcinoma (UPSC) — typically a cancer of older women striking long after menopause.

It is not believed to be tied to increased oestrogen exposure. Indeed, ‘there are no risk factors’, as two researchers bluntly put it.

Cancer can take decades to develop, so in most cases it is almost impossible to work out what triggered a rogue cell to become cancerous. It has been estimated that every second, four million cells in our body are dividing, copying their DNA (their genetic blueprint). With every division there are imperfections. Some can go catastrophically wrong.

Research has found some of the causes of cancer: smoking, environmental pollutants and infections (for example, the human papillomavirus that can cause cervical cancer). Naturally occurring radiation from sunlight and radon gas also contribute.

Evidence also shows that a large percentage of cancer cases can be attributed to lifestyle. Opinion still varies on just what is most important when it comes to food — how much red and processed meat is bad, how many fruits and vegetables are good.

Nancy always ate her vegetables — obsessively, it sometimes seemed — and her fibre, bringing home breakfast cereals that tasted like their cardboard box. But there was nothing rigid about Nancy’s dietary pursuits. We both loved steaks and hamburgers (though for penance would have fish sometimes).

But the science on food is not persuasive, giving way to suspicion that lack of exercise and excess weight are more to blame.

Our cells are constantly exchanging chemical signals, conferring on when to start multiplying and creating new tissue. As each cell receives this information, it sends instructions to its nucleus for activating the appropriate genes.

A cancer cell is one that, because of some fault, has cut itself out of this discussion. Random events — triggered by a cosmic ray, a carcinogenic chemical, or dumb luck — must have altered the DNA inside one of Nancy’s cells, causing it to lose touch.

These errors happen all the time. We usually don’t get cancer because other genes react to sudden bursts of activity by reining back the rogue cell’s growth. But another bad mutation in the cell can cause that safeguard to fail, by blocking the body’s tumour-suppressing genes.

Even if that safeguard fails, the rogue cell can sense its own inner turmoil and will send itself suicide signals, killing itself for the common good — a process called apoptosis. But yet another bad mutation can undermine this defence.

That still leaves another barrier against runaway growth. A normal cell can divide only 50 or 60 times. The count is kept by telomeres — caps on the ends of your chromosomes (which carry your DNA). These telomeres get shorter each time around, and once they fall below a certain size, the cell is taken offline.

Once again, however, there is a problem. Cells like those in the immune system, which must divide repeatedly, manufacture telomerase, an enzyme that keeps replacing the caps on the chromosomes’ ends. A cancer cell will learn this trick, acquiring through the trial and error of mutation the information needed to produce its own telomerase.

It can then replicate indefinitely, producing a mass of mutant offspring — a tumour. That is still not enough to give you cancer. It takes more mutations for the cell to learn how to invade surrounding tissues, to become malignant. And, even then, the tumour can only grow to the size of a ballpoint pen’s tip before it risks starving for lack of food or drowning in its own waste.

To continue expanding, it must somehow reach into the circulatory system and suck it like a vampire. With these nutrients, the cells multiply even more aggressively, increasing the probability of more mutations.

The cancer spins out one cell variation after another — hopeful monsters trying to gain an upper hand. Some cells might learn to consume energy more efficiently, others to suppress the immune system. Others still will learn to send signals that con healthy cells into growing new blood vessels that feed the tumour and new tissues that help to build it.

Finally, the fittest cancer cells will set sail into the bloodstream and explore new ground. Their chances of survival are low. Most perish immediately in the river of blood — smashed against a vessel wall, pinched to death in an impassable strait or destroyed by the body’s immune cells.

So many dangers — which make it all the more extraordinary that some beat the odds.
Some research suggests that the swimming cancer cells can surround themselves with platelets (blood-clotting cells) for protection. Or if they get stuck inside a tiny capillary, some may be able to jettison enough of their own bodies to slim down and squeeze through.

However they survive the journey, they still must find a berth downstream. Here, again, most will perish. After 24 hours only 0.1 per cent are alive, and less than 0.01 per cent go on to form tumours. The odds seem almost comforting, but of all the seeds a tumour can shed, it takes only one to start another cancer. Once the cancer cells arrive at a promising location, a new cascade of events begins. They exchange signals with the natives — the cells of the tissue they are set to invade — recruiting their help in coming ashore.

If co-operation is not forthcoming, a cancer cell might lie dormant in its new home, hiding for years until reawakened by some new random event.

When the cancer cells have finally established their first colony, some will move on to other sites. They may even return to the mother tumour to rejoin the battle at home. This self-seeding might help explain the recurrence of cancers that surgeons are confident they had completely removed.

Besides the blood, there is another course the seeds can follow from the tumour — through the lymphatic vessels. The lymph system is a primitive sewer, sluggishly draining clear, watery waste from cracks between cells. Along the way it is filtered by the lymph nodes.

Tumours can learn to create connections to the lymphatic system. They may even send signals to a nearby lymph node, instructing it to sprout more blood vessels to accommodate the forthcoming invasion.

The lymphatic system — this key component of the body’s defences designed to filter out infectious organisms, produce white blood cells and generate antibodies — is turned into a tumour’s ally.

The first sign is a lump growing inside a lymph node, the barrier whose purpose is to stop such attacks. That apparently is what happened with Nancy.

What little has been published about her type of cancer could hardly have been more discouraging: ‘Survival rate is dismal,’ it said.

After her surgery Nancy began the gruelling process of chemotherapy, followed by radiotherapy that would irradiate her entire pelvis.

The risk is radiation scars causing bowel obstructions and damaging internal organs and also the lymphatic system, which can cause chronic swelling of the torso and limbs. Nancy’s right leg swelled — while we were assured it was probably temporary, it never went away.

It wasn’t such a bad compromise, Nancy would say, for being alive.
Every few months after her treatment ended, Nancy went for blood tests. She also had a body scan twice a year, and every time it showed she was clear of tumours.

In the fifth year after cancer she bought a horse — something she had wanted since she was young. The following year she bought two-and-a-half acres of land with barns and stables. She was determined not to waste a day of a future she almost lost.

The following year our marriage ended, 17 years after it had begun. For a long time our lives had been diverging.

The cancer had brought us closer but now it was gone. Brushing so near death makes a person think about how she wants to spend what is left of life. Nancy had her reasons for deciding it was not with me.

Inside my body, meanwhile, ten trillion cells are battling the same inevitable slump towards failure — and the possibility of cancer. It is eerie to think that inside each one, invisible to the eye, so much is happening.

The cell doesn’t know it has DNA or telomeres. There are no labels, no genetic alphabet written anywhere, no instructions.

Written by George Johnson for the Daily Mail, August 27, 2013.

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