Obesity's Role in Cancer

Packing on the pounds gets a well-deserved bad rap. Most Americans understand that excess weight contributes to heart disease and diabetes, not to mention the urge to hide behind the kids in family photos. But obesity as a risk factor for cancer?

That seems to be the case. An increasing number of studies are finding that overweight and obese people are more likely to develop cancer of various kinds. At least half a dozen types of cancer are believed to be directly affected by weight.

"As time goes on, we're realizing that obesity is related to more cancers than we originally suspected," said Dr. Donald Hensrud, an associate professor of preventive medicine and nutrition at the Mayo Clinic College of Medicine.

Researchers are unable to prove that obesity actually causes cancer because requiring people to either gain weight or keep their weight down in clinical trials would be impossible. Most of the data come from observational studies, in which people who are thinner are probably doing many things differently than their heavier counterparts. Any number of those factors might be responsible for the difference in cancer rates.

Still, the evidence is "convincing" for a cause-and-effect relationship between obesity and postmenopausal breast, colon, endometrial, esophageal, kidney and pancreas cancer, according to a 2007 report from the World Cancer Research Fund and the American Institute for Cancer Research. The report also cited obesity as a "probable" cause of gallbladder cancer.

Scientists aren't sure how obesity might affect cancer risk, but "there are some plausible biological mechanisms by which this may occur," said Dr. Patricia Ganz, director of cancer prevention and control research at UCLA's Jonsson Comprehensive Cancer Center.

One popular explanation is that extra weight boosts the body's production of hormones such as estrogen, insulin and insulin-like growth factor 1 — all of which have the potential to promote the growth of certain tumors. Another possibility is that fatness contributes to cancer growth by causing cells to divide more rapidly.

Mechanical factors may play a role in certain types of cancer. In the case of esophageal cancer, the culprit seems to be acid reflux. People who are overweight are more likely to experience chronic reflux, which can lead to precancerous changes by eroding the lining of the esophagus.

The suspected higher risk of gallbladder cancer might be explained by the increased tendency of obese people to develop gallstones. These stones cause inflammation that could promote cancer.

Putting a number on it

Rates of obesity have steadily increased over the past few decades, more than doubling from 15% of adults in the early 1970s to 34% of adults in 2005-06, according to data from the National Health and Nutrition Examination Survey. Cancer rates also increased somewhat during this period, from a rate of 4 in 1,000 in 1975 to 4.56 per 1,000 in 2006 —although rates peaked in 1992 and have since been on the decline.

Scientists don't know how much of this increase in cancer is real. Much of it appears to reflect the fact that we now regularly go looking for cancer with mammograms and prostate specific antigen tests, which is one more reason why the relationship between obesity and cancer is so difficult to study.

The World Cancer Research Fund and the American Institute for Cancer Research made an attempt to quantify the relationship in a 2009 policy report. The report concluded that excess body weight has the largest effect on endometrial cancer, causing an estimated 49% of cases. This translates into an extra 20,700 people with endometrial cancer per year.

The policy report also calculated that being overweight or obese causes 35% of esophageal cancers (5,800 people per year), 28% of pancreatic cancers (11,900 people per year), 24% of kidney cancers (13,900 people per year), 21% of gallbladder cancers (2,000 people per year), 17% of breast cancers (33,000 people per year) and 9% of colon cancers (13,200 people per year) .

Dr. Moshe Shike, an attending physician at Memorial Sloan-Kettering Cancer Center whose research focuses on cancer prevention, said he was skeptical about the idea of putting a number on something so slippery, saying that this implies accuracy where none exists. "We don't know the magnitude of the effect," he said.

Dr. Michael Thun, head of epidemiologic research for the American Cancer Society, agreed that the percentages are imprecise, but pointed out that numbers are often the best way to get results. "Numbers carry a strong message, just as estimates of death caused by smoking were very important to tobacco control," he said.

Most of the studies on weight and cancer risk define obesity using body mass index (BMI), a number that accounts for weight in relation to height. Someone who stands 5-foot-7 is considered "overweight" at 159 pounds and "obese" at 191 pounds. A third of Americans are overweight, and another third are obese.

But the real culprit is fat, not weight, so a football player-type with lots of muscle and little flab would not be at increased risk even if his BMI fell into the "overweight" category.

The effects of weight loss

If excess weight increases the risk of cancer, can losing weight reduce the risk? Preliminary research suggests that it might. At least two large, published studies have found that people who undergo gastric bypass surgery are significantly less likely to develop cancer or die from it than severely obese people who don't undergo the weight-loss procedure.
 

People who have been diagnosed with certain cancers, including breast, prostate and colorectal cancer, also seem to have a worse prognosis if they're overweight or obese, according to Dr. Jeffrey Meyerhardt, an assistant professor of medicine at Harvard Medical School. Preliminary studiessuggest that weight loss might reduce this risk.

For example, a clinical trial called the Women's Intervention Nutrition Study that was published in the Journal of the National Cancer Institute in 2006 randomly assigned breast-cancer survivors to either a low-fat diet or their regular diet. Not only did the women on the low-fat diet wind up an average of six pounds lighter than their control-group counterparts, they had a reduced risk of cancer recurrence at five years.

Studies like this one fail to answer the question of which played a bigger role, the types of foods eaten or the amount of weight lost. But as randomized trials fail to find cancer-fighting benefits for specific dietary components, such as fiber (long suspected of decreasing the risk of colon cancer), the evidence increasingly points toward weight as the key factor.

"A healthy diet is good for avoiding obesity, but it's not clear that diet itself impacts the prognosis of most cancers," said Meyerhardt. A possible exception, he said, is colon cancer; his own research has linked recurrence and reduced survival to a diet high in red meat, refined grains and sugary desserts.

Shike said that the No. 1 lifestyle measure people can take to reduce their risk of cancer is to avoid smoking and secondhand smoke, followed by maintaining a healthy weight.

Physical activity and diet also play a role in cancer prevention, he said, primarily through their effect on weight. In addition, the American Cancer Society recommends no more than one alcoholic drink per day for women or two per day for men.

Now, the exceptions

Much remains unknown about the overall role obesity plays in cancer risk. For some cancers, of course, it appears to play little or no role. And for a few types of cancer, the incidence is actually lower in overweight people.

Contrary to its relationship with postmenopausal breast cancer, extra weight seems to offer women some protection against premenopausal breast cancer. A possible explanation is that obesity interferes with ovarian function in younger women, causing reductions in estrogen. Only about 20% to 25% of breast cancer cases occur before menopause, however, so weight control is still related to an overall reduction in breast cancer risk.

Another exception to the rule is lung cancer, for which the risk steadily increases as weight drops. The reason? "Smokers tend to be leaner than nonsmokers," said Dr. Elizabeth Platz, an associate professor at the Johns Hopkins Bloomberg School of Public Health. Cigarette-induced slimness comes at a steep price, though: a dramatically increased risk of lung cancer, among other diseases.

The incidence of prostate cancer also seems to be lower for overweight men. In this case, the apparent decrease may occur because the extra weight makes screening and diagnostic tests less sensitive, according to Platz. If so, delays in diagnosis might explain why research has linked obesity to an increased risk of aggressive prostate cancer.

Childhood cancers and those of the brain, nervous system and musculoskeletal system appear to be unaffected or little affected by weight, according to the World Cancer Research Fund and the American Institute for Cancer Research policy report.

But don't forget

No matter what researchers ultimately reveal about the role of weight in cancer, weight control remains an essential part of staying healthy.

"If body fatness were totally unrelated to cancer, the message would still be the same, because of the importance of weight control for heart disease, stroke, diabetes, joint pain and other conditions," said Dr. Tim Byers, a professor of epidemiology at the Colorado School of Public Health.

He also emphasized that staying trim is no guarantee of a cancer-free life. "It's a risk factor, that's all, just like bad brakes and drunk driving are risk factors for traffic accidents."