Genes Hike Melanoma Risk Even in Those Who Tan Well

TUESDAY, April 21 (HealthDay News) -- If you have dark eyes, dark hair and tan easily, you might think you don't have to worry much about melanoma.

But new research shows that variations of a particular gene can raise the risk of this deadly skin cancer, even in people whose ability to tan may make them appear to be at low risk. Having a variant of the melanocortin-1 receptor gene (MCIR) puts people who have dark hair, dark eyes and who tan easily at more than twice the risk of getting melanoma as those with similar complexions who don't have the variant.

"Traditionally, a clinician might look at a person with dark hair who did not sunburn easily and classify them as lower risk for melanoma, but that may not be true for all people in the population," said Peter Kanetsky, an assistant professor of epidemiology at the University of Pennsylvania School of Medicine and a co-author of research on the topic. "Just because you tolerate sun exposure fairly well doesn't mean that you're not at increased risk for melanoma."

The findings were to be presented Tuesday at the American Association for Cancer Research annual meeting in Denver.The researchers examined 779 people with melanoma at the Pigmented Lesion Clinic at the University of Pennsylvania and 325 people who did not have melanoma. They analyzed the participants' MCIR variant status and had them fill out questionnaires about sun exposure, ability to tan and their physical appearance.

Previous research has identified more than 50 versions of the MCIR gene, about four of which have been linked to an increased risk for melanoma, Kanetsky said. In the study, about 70 percent of the healthy participants had some variant of the gene, and nearly 27 percent had one of the four high-risk variants. Among the participants with melanoma, about 78 percent had a gene variant and 43 percent had a high-risk variant.

Those who had dark eyes and an MCIR variant had a about a threefold greater risk of developing melanoma than did those with dark eyes but no variant. Those who did not freckle but who had the high-risk variant had an eightfold increased risk, and those who tanned moderately or deeply after repeated sun exposure had about twice the risk. "They're finding that in people who are able to tan, who conceivably could have been educated not to worry about the sun, the presence of those variants does confer increased risk of developing melanoma, compared to those who do not have the MCIR variant," said Dr. David Fisher, chief of dermatology at Massachusetts General Hospital and a dermatology professor at Harvard Medical School.

Having a variation of the MCIR gene has been shown in prior research to be associated with having red hair, freckles and fair skin. It's also been associated with a higher risk of melanoma, even when adjusting for lighter skin tone, lighter hair and lighter eyes, Kanetsky said.

In this study, the MCIR variant in people with red or blond hair did not affect melanoma rates. Researchers are not sure why the MCIR variant didn't seem to boost melanoma risk in the fair-haired group, but they suspect that other biological processes or genes could be at work, causing the increased melanoma risk. Melanoma, the most serious form of skin cancer, is highly curable when caught early. In 2008, an estimated 8,420 people in the United States died from it, according to the American Cancer Society. There were about 62,000 new cases.

Currently, there is no commercially available test for MCIR variants.

In Cancer, a Deeper Faith

By Dana Jennings

We are about to enter a holy few days for Jews and Christians. Passover starts at sundown tomorrow, and Easter is Sunday. But then again, when you’re a cancer patient, each day is a holy day – no matter what your beliefs.

I converted to Judaism five years ago, after decades spent stumbling toward God. That faith has helped sustain me this past year, from the diagnosis of my prostate cancer, through surgery, and through radiation and hormone treatment when it was learned that I had an aggressive cancer.

I am not a fool. I am a patient with Stage T3B cancer and a Gleason score of 9. I need the skills and the insights of the nurses and doctors who care for me. But they don’t treat the whole man. Medicine cares about physical outcomes, not the soul. I also need — even crave — the spiritual antibodies of prayer, song and sacred study.

And it’s a powerful thing to know that others are praying for your return to health. My faith reminds me that I am not alone, that I am part of a larger whole, part of an ancient tradition and a timeless narrative. Disease often makes us feel cut off from community, even from ourselves, and faith helps defy that sense of isolation.

One of our cultural verities about serious illness is that it often challenges our faith. But for me, if anything, having cancer has only deepened it, heightened it.

I have spent the past year in the dark ark of cancer, and there is no question that I have become a new man. I’ve been granted a wisdom that only arrives at the rugged confluence of middle age and mortality. And I know, soul deep, that I have not been cut open, radiated, and tried physically and spiritually so that I can merely survive, become a cancer wraith. Since my diagnosis — after shaking off the initial shock — I have kept asking myself, in the context of my belief: What can this cancer teach me?

The most surprising thing I’ve learned is that cancer can be turned toward blessing. Through the simple fact of me telling my cancer stories on this blog, many of you readers, in turn, have told your own stories. And that mutual sharing of our tales has changed my life for the good. Rabbi Abraham Joshua Heschel said, “Life is not meaningful … unless it is serving an end beyond itself, unless it is of value to someone else.”

None of us would choose to have cancer. But getting this unexpected mortality check has deepened my appreciation of and connection to this life. Each moment holds out the promise of revelation.

Cancer, like faith, urges us toward the essential in our lives, toward love and kindness and paying attention to the smallest, smallest detail. We suddenly understand that ice chips spooned into a parched mouth, that being able to simply urinate, are gifts, the kinds of ordinary gifts that make up our lives.

So, yes, Easter and Passover beckon with their vernal tales of exile, renewal and redemption. I found out exactly one year ago today that I had prostate cancer. But I won’t know for a very long time whether I’ve been truly passed over.

Whatever happens, though, I’m ready.

Can a High-Fat Diet Beat Cancer?

The women's hospital at the University of Würzburg used to be the biggest of its kind in Germany. Its former size is part of the historical burden it carries — countless women were involuntarily sterilized here when it stood in the geographical center of Nazi Germany.

Today, the capacity of the historical building overlooking the college town, where the baroque and mid-20th-century concrete stand in a jarring mix, has been downsized considerably. And the experiments within its walls are of a very different nature.

Since early 2007, Dr. Melanie Schmidt and biologist Ulrike Kämmerer, both at the Würzburg hospital, have been enrolling cancer patients in a Phase I clinical study of a most unexpected medication: fat. Their trial puts patients on a so-called ketogenic diet, which eliminates almost all carbohydrates, including sugar, and provides energy only from high-quality plant oils, such as hempseed and linseed oil, and protein from soy and animal products.

What sounds like yet another version of the Atkins craze is actually based on scientific evidence that dates back more than 80 years. In 1924, the German Nobel laureate Otto Warburg first published his observations of a common feature he saw in fast-growing tumors: unlike healthy cells, which generate energy by metabolizing sugar in their mitochondria, cancer cells appeared to fuel themselves exclusively through glycolysis, a less-efficient means of creating energy through the fermentation of sugar in the cytoplasm. Warburg believed that this metabolic switch was the primary cause of cancer, a theory that he strove, unsuccessfully, to establish until his death in 1970.

To the two researchers in Würzburg, the theoretical debate about what is now known as the Warburg effect — whether it is the primary cause of cancer or a mere metabolic side effect — is irrelevant. What they believe is that it can be therapeutically exploited. The theory is simple: If most aggressive cancers rely on the fermentation of sugar for growing and dividing, then take away the sugar and they should stop spreading. Meanwhile, normal body and brain cells should be able to handle the sugar starvation; they can switch to generating energy from fatty molecules called ketone bodies — the body's main source of energy on a fat-rich diet — an ability that some or most fast-growing and invasive cancers seem to lack.

The Würzburg trial, funded by the Otzberg, Germany–based diet food company Tavartis, which supplies the researchers with food packages, is still in its early, difficult stages. "One big problem we have," says Schmidt, sitting uncomfortably on a small, wooden chair in the crammed tea kitchen of Kämmerer's lab, "is that we are only allowed to enroll patients who have completely run out of all other therapeutic options." That means that most people in the study are faring very badly to begin with. All have exhausted traditional treatments, such as surgery, radiation and chemo, and even some alternative ones like hyperthermia and autohemotherapy. Patients in the study have pancreatic tumors and aggressive brain tumors called glioblastomas, among other cancers; participants are recruited primarily because their tumors show high glucose metabolism in PET scans.

Four of the patients were so ill, they died within the first week of the study. Others, says Schmidt, dropped out because they found it hard to stick to the no-sweets diet: "We didn't expect this to be such a big problem, but a considerable number of patients left the study because they were unable or unwilling to renounce soft drinks, chocolate and so on."

The good news is that for five patients who were able to endure three months of carb-free eating, the results were positive: the patients stayed alive, their physical condition stabilized or improved and their tumors slowed or stopped growing, or shrunk. These early findings have elicited "very positive reactions and an increased interest from colleagues," Kämmerer says, while cautioning that the results are preliminary and that the study was not designed to test efficacy, but to identify side effects and determine the safety of the diet-based approach. So far, it's impossible to predict whether it will really work. It is already evident that it doesn't always: two patients recently left the study because their tumors kept growing, even though they stuck to the diet.

Past studies, however, offer some hope. The first human experiments with the ketogenic diet were conducted in two children with brain cancer by Case Western Reserve oncologist Linda Nebeling, now with the National Cancer Institute. Both children responded well to the high-fat diet. When Nebeling last got in contact with the patients' parents in 2005, a decade after her study, one of the subjects was still alive and still on a high-fat diet. It would be scientifically unsound to draw general conclusions from her study, says Nebeling, but some experts, such as Boston College's Thomas Seyfried, say it's still a remarkable achievement. Seyfried has long called for clinical trials of low-carb, high-fat diets against cancer, and has been trying to push research in the field with animal studies: His results suggest that mice survive cancers, including brain cancer, much longer when put on high-fat diets, even longer when the diets are also calorie-restricted. "Clinical studies are highly warranted," he says, attributing the lack of human studies to the medical establishment, which he feels is single-minded in its approach to treatment, and opposition from the pharmaceutical industry, which doesn't stand to profit much from a dietetic treatment for cancer.

The tide appears to be shifting. A study similar to the trial in Würzburg is now under way in Amsterdam, and another, slated to begin in mid-October, is currently awaiting final approval by the ethics committee at the University Hospital in Tübingen, Germany. There, in the renowned old research institution in the German southwest, neuro-oncologist Dr. Johannes Rieger wants to enroll patients with glioblastoma and astrocytoma, aggressive brain cancers for which there are hardly any sustainable therapies. Cell culture and animal experiments suggest that these tumors should respond particularly well to low-carb, high-fat diets. And, usually, these patients are physically sound, since the cancer affects only the brain. "We hope, and we have reason to believe, that it will work," says Rieger.

Still, none of the researchers currently studying ketogenic diets, including Rieger, expects it to deliver anything close to a universal treatment for cancer. And none of them wants to create exaggerated hopes for a miracle cure in seriously ill patients, who may never benefit from the approach. But the recent findings are difficult to ignore. Robert Weinberg, a biology professor at MIT's Whitehead Institute who discovered the first human oncogene, has long been critical of therapeutic approaches based on the Warburg effect, and has certainly dismissed it as a primary cause of cancer. Nevertheless, he conceded, in an email, for tumors that have been affected by the ketogenic diet in animal models, "there might be some reason to go ahead with a Phase I clinical trial, especially for patients who have no other realistic therapeutic options."

Richard Friebe is executive editor of the German science magazine SZ Wissen