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Fat chance: extra pounds can increase your cancer risk.

If you're like most people, you're at least a few pounds overweight. So what?

Losing weight would lower your risk of diabetes, heart disease, high blood pressure, and arthritis. No surprise there. And it wouldn't hurt the next time you try to squeeze into last year's bathing suit.

What many people don't know is that extra pounds mean an extra risk of cancer--of the breast, colon, esophagus, kidney, uterus, and possibly more.

"We estimate that 90,000 deaths due to cancer could be prevented each year in the U.S. if men and women could maintain normal weight," says Eugenia Calle, director of analytical epidemiology at the American Cancer Society in Atlanta.

"After tobacco smoking, obesity is the principal cause of cancer in the U.S." says Dimitri Trichopoulos of the Harvard school of Public Health.

Suddenly, that spare tire looks more ominous than it did before.

Do chubby people have a higher risk of cancer?

"The evidence Is very strong for a number of cancer sites," says Walter Willett, who chairs the nutrition department at the Harvard School of Public Health.

The plumpest people have a higher risk of cancers of the breast, colon, esophagus, kidney and uterus, according to the World Health Organization's international Research on Cancer. (1,2)

"We've been trying to get that information out to the public," says Willett.

Last April, the American Cancer Society (ACS) added more potential cancers when it released the biggest study ever done on excess weight and cancer deaths. (3) (It tracked more than 900,000 people for 16 years.)

"Because it was a very large study, we could look at a wide range of cancers," says lead author Eugenia Calle.

The risk of dying of cancers like liver, pancreas, cervix, gallbladder, non-Hodgkin's lymphoma, and multiple myeloma was higher in heavier people. "But we don't have enough data from other studies to know if those links are real," she adds.

The rapidly expanding American waistline contributes to 14 percent of cancer deaths in men and 20 percent in women, says the ACS. That's partly because so many of us are fat.

"With something as prevalent as obesity, even a small increase in risk can account for a large number of cancers," says Calle.

For most cancers, the fattest people have twice the risk of those who aren't overweight, and the overweight-but-not-obese have only a 20 to 60 percent increased risk.

"It's not smoking and lung cancer" acknowledges Willett. (Cigarettes multiply the risk of lung cancer ten-fold.) But the threat posed by smoking is unusual.

"Very few exposures are on the order of tobacco," agrees Rachel Ballard-Barbash of the National Cancer Institute (NCI). "Obesity raises the risk of heart disease only two-fold, for example."

Obesity raises the risk of dying of breast cancer about as much as mammography lowers it, says Willett. "They're both modest, but important."

How do bigger bellies, hips, and thighs lead to tumors? It depends on the cancer but researchers have a theory that ties at least some of them together.

Mutations or damage to DNA can "initiate" a cancer by turning off normal cell regulation. "But a cancer has to be stimulated to grow," says Calle.

That's where obesity comes in. "Obesity raises levels of peptide hormones like insulin and steroid hormones like estrogen," she explains. "Both hormones stimulate cell growth."

Of all the cancers linked to weight, researchers are most interested in the cancer that's most likely to strike women.

Breast Cancer

For years, it looked as though weight had no impact on breast cancer. "We didn't see the effect until we looked only at postmenopausal women who had never been exposed to hormone replacement therapy," explains Ballard-Barbash.

In premenopausal women, obesity actually lowers the risk of breast cancer, so that muddied the waters.

"It's unclear why weight protects against breast cancer in younger women, at least in affluent countries like the U.S.," says Regina Ziegler, a nutritional epidemiologist at the NCI. One possibility: Obesity interferes with ovulation, and that reduces exposure to estrogen.

But excess weight protects only the heaviest premenopausal women. And those women have a higher risk of diabetes and other illnesses, so "it shouldn't be an excuse to avoid losing weight," Ziegler adds.

Even when researchers looked only at postnenopausal women, weight had little impact on cancer risk ... until Willett's team excluded women who take hormone replacement therapy.

"Women who were taking hormones were at higher risk of breast cancer no matter what their weight, because they were taking pharmacological levels of estrogen," he says.

When he looked at women who were not taking estrogen, the impact of weight was clear. "Obese women had circulating estrogen levels that were three times higher than lean women," says Willett. "That's a huge difference."

For years, researchers have been stumped by the lower rates of breast cancer in Japanese women.

"Obesity explains a big piece of the difference between Japan and the U.S.," says Willett. "Almost all Japanese women are in the normal weight range and they don't take hormones."

And it's not just obese women who need to worry. In the American Cancer Society study, the risk of most cancers started to climb at a Body Mass Index (BMI) of 25, which is the dividing line between "normal" and "overweight." But for breast cancer, the risk was higher at the heavier end of the normal range (23.0 to 24.9) than at the leaner end (18.5 to 22.9). (To find your BMI, see "Rate Your Weight," p. 6.)

"Many people start out at age 18 with a BMI of 18 or 19," explains Willett. Women who don't gain more weight have the lowest risk of breast cancer. "Women who gain even six to eight pounds have a small increase in risk, and it goes up stepwise from there."

Extra pounds are also a strike against women who have already been diagnosed with breast cancer. "Excessive weight and obesity increase the risk of getting breast cancer and decrease survival rates once you have breast cancer," says Calle. "Our data reflect both."

How could gaining weight affect the breast?

Overweight postmenopausal women have more estrogen because fat cells convert androgens to estrogen. "In premenopausal women, ovaries are the major source of estrogen," explains Ziegler. "But when ovaries stop producing estrogen, the effect of fat cells is more apparent."

Researchers haven't nailed down estrogen as the link between weight and breast cancer, she cautions. "But weight fits right in with the constellation of risk factors for breast cancer," like how many years a woman menstruates, whether she takes replacement estrogen, and how much alcohol she drinks. "They all work by raising circulating hormone levels," says Ziegler.

"Weight should matter even more now that women are going off hormones in droves," she adds. But that also gives researchers hope.

"If we can get women to take off weight, tumors might be initiated but they won't go anywhere," says Ziegler. Many women have dysplasia (a precancerous abnormality) or carcinoma in situ (a malignancy that hasn't spread to neighboring cells). "If tumor growth isn't promoted by excess weight, a woman may never have a problem in her lifetime," she explains.

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Scientists don't have proof that women can cut their risk of breast cancer by losing weight, but they're optimistic. "We have every reason to believe that losing weight would reduce risk because we know that risk goes back down when women stop taking estrogen," notes Willett.

What's more, weight loss might lower risk fairly quickly. "In one of our studies, recent weight gain and current weight were the most critical risk factors for breast cancer," says Ziegler. "If women were to adopt lifestyles that lower circulating hormone levels, we might see an impact on breast cancer in five or ten years."

That's not trivial when it comes to a cancer that has few easy-to-change risk factors. "Avoiding weight gain is one of the few things women can do to lower their risk of breast cancer," says Willett.

And the impact could be substantial. "If women didn't take estrogen and maintained a healthy weight, it would reduce the incidence of breast cancer by a third and mortality rates by half," he predicts.

It's not just breast cancer. Excess weight also raises the risk of colorectal, esophageal, kidney, and uterine cancer, says the International Agency for Research on Cancer. For other cancers--gallbladder, pancreas, and prostate--the research is less clear.

Colorectal Cancer

Colorectal cancer kills more Americans than any cancer other than lung. High blood insulin levels may be a culprit.

"If you're obese, and especially if you carry extra weight around your abdomen, you run the risk of living in a state of high circulating insulin levels," explains the American Cancer Society's Eugenia Calle.

That sets off a chain of events that leads to higher levels of insulin-like growth factors, or IGFs, which promote cell growth.

Insulin might also explain why active people have a lower risk. Exercise helps put a lid on insulin levels, even if you're overweight.

Esophageal Cancer

Only 13 out of 100 people survive five years after a diagnosis of esophageal cancer. And the obesity epidemic might explain why one of the two major kinds of esophageal cancer (adenocarcinoma) is on the rise. "Being overweight increases the risk of acid reflux," says Calle.

If acid from the stomach regularly backs up into the lower esophagus, it can eventually cause squamous cells (which usually line the esophagus) to become glandular cells (which usually line the stomach). And that can lead to cancer.

"Adenocarcinoma of the esophagus is caused by local acid irritation due to a mass of fat in the abdomen," says Willett.

Gallbladder Cancer

The gallbladder is a small, pear-shaped organ located underneath the liver, just below the right side of your rib cage. The liver makes the bile that helps digest fats in the small intestine. The gallbladder concentrates and stores bile.

"Obesity increases the risk of gallstones," explains Calle, "and people who get more gallstones have a higher risk of gallbladder cancer."

Every year, between 6,000 and 7,000 people are diagnosed with gallbladder cancer, and about 3,600 people die of the disease. Most patients are women who are 70 or older.

Kidney Cancer

Kidney cancer is the seventh most common cancer among men and the eleventh most common among women. The odds of surviving five years are 62 percent.

"The cancer is still common and the relationship with obesity is strong," says Willett.

Blood in the urine or a lump near the kidney is the most common symptom, but in its early stages, there may be no symptoms at all.

"Kidney cancer is especially related to abdominal obesity, so insulin may be involved, but we don't really have an explanation," says Harvard's Dimitri Trichopoulos.

Pancreatic Cancer

The pancreas secretes insulin, and the hormone may explain why overweight people seem to have a higher risk. Increased levels of insulin lead to higher levels of insulin-like growth factors (IGF).

"A constellation of factors suggests that IGF may be a factor in pancreatic cancer" says Willett. "But it's difficult to prove one way or the other."

One reason is that pancreatic cancer is such a swift killer. "It's hard to study because people die so soon after they are diagnosed," says the National Cancer Institute's Rachel Ballard-Barbash.

Cancer of the pancreas will strike an estimated 30,700 Americans--and kill 30,000--this year. Only four out of every 100 victims survive for five years.

Prostate Cancer

Overweight men were more likely than normal-weight men to die of prostate cancer in the recent American Cancer Society study. But researchers think that's because excess weight lowers a man's odds of surviving--not getting--the illness.

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"When you look at the literature, there's not much evidence that obesity increases the risk of prostate cancer," says Calle.

But once a man is diagnosed with the disease, "some studies show a higher risk of either death or advanced disease for overweight men," she adds.

Uterine Cancer

The heaviest women are six times more likely to get cancer of the endometrium (the lining of the uterus) than women who aren't overweight. As with breast cancer the risk starts to climb even for women who are not yet overweight.

"We saw a higher risk for heavy-normal women than for lean-normal women," says the American Cancer Society's Eugenia Calle.

Estrogen is clearly a culprit, say researchers. "We've known for some time that unopposed estrogen therapy increases the risk of endometrial cancer," says Ballard-Barbash. "Unopposed" means estrogen without progestin.

That's why most women on hormone replacement therapy take both hormones. (Women who've had a hysterectomy take estrogen only.) "Combined estrogen-progestin also increases the risk of endometrial cancer," adds Ballard-Barbash, "but not as much."

The Bottom Line

"Avoiding weight gain, along with not smoking, is one of the most important things people can do to protect their long term health," says Harvard's Walter Willett.

The goal isn't just to keep your BMI in the "normal" range, but to keep your weight stable from your 20s on.

A heavy-normal weight is often not ideal, says Willett. "If you start out with a BMI of 18, you can put on 30 or 40 pounds and still have a BMI under 25." (Roughly every seven pounds moves your BMI up of down one point.) "You're technically in the healthy range, but your weight will increase your risk of breast cancer, as well as diabetes, heart disease, and stroke."

Of course, the "stay lean" message is a little late for many people. But the "lose weight" message isn't, especially when shedding excess pounds has so many benefits beyond cancer.

"You're buying a decreased risk for diabetes, heart disease, hypertension--almost every disease in the book," says the National Cancer Institute's Regina Ziegler.

And for some health problems, the weight loss needn't be large. "The impact on diabetes is huge," says Willett. "In our study, women who reported losing only about ten pounds lowered their risk of diabetes by 80 percent."

Could fear of cancer motivate people to lose weight where other diseases have failed?

"Cancer scares people more than heart disease so it may make a difference," says Trichopoulos. But it's not going to be easy.

"Eating is a response to stress and it's one of the few predictable pleasures in life," he adds. "Love and children are pleasures, but they're not predictable. Food is right there." His advice for the overweight: "Cut whatever you're eating by 30 percent."

People also need to see through the food industry's attempts to fatten us up.

"We have to break free from 'all-youcan-eat-for-$2.99,'" says Calle. "We need to grab the bull by the horns if we want to turn this problem around."

Extra Weight & Cancer Risk (Women)

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As a woman's BMI rises above the normal range (18.5 to 24.9), her risk of dying of breast, kidney, uterine, and several other cancers also rises. For example, the risk of dying of breast cancer is 34 percent higher for women who are overweight (a BMI between 25.0 and 29.9) than for women who are normal-weight. For the most obese women (a BMI of 40 or higher), the risk of dying of breast cancer is double, the risk of kidney cancer is nearly five times higher, and the risk of uterine cancer is six times higher.

Source: New Eng. J. Med. 348: 1625, 2003.

Extra Weight & Cancer Risk (Men)

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As a man's BMI rises above the normal range (18.5 to 24.9), his risk of dying of colorectal, esophageal, kidney, and several other cancers also rises, though not as dramatically as it does for cancers of the uterus or kidney in women. For example, the risk of dying of colorectal cancer is 20 percent higher for men who are overweight (a BMI between 25.0 and 29.9) than for men who are normal-weight. For the most obese men (a BMI of 35 of higher), the risk is not quite double (84 percent higher).

Source: New Eng. J. Med. 348: 1625, 2003.

Rate Your Weight

Your Body Mass Index (BMI) gauges your weight in relation to your height. Find your weight at the bottom of the graph. Go straight up from that point until you come to the horizontal line that matches your height. Then check to see which group you fall into.

Although a BMI between 18.5 and 24.9 is considered normal, the risk of breast and uterine cancers (and diabetes) starts to climb above a BMI of 23.

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Note: BMI shouldn't be used to evaluate the weight of children, the frail elderly, serious bodybuilders, or pregnant or breastfeeding women. If your extra weight comes from muscle, not fat, you may have a high BMI even though you're healthy. Frail or older people may be unhealthy even though they have a low BMI.

Source: adapted from Dietary Guidelines forn Americans, 2000, U.S. Department of Agriculture and U.S. Department of Health and Human Services.

How to Lose It

Preliminary research suggests that a lower-carbohydrate diet may be the quickest way to lose excess weight. But the National Weight Control Registry, which has tracked nearly 3,000 people who have lost an average of 70 pounds and kept it off for six years, reports different results.

Most successful weight-losers in the registry eat a lower-fat, lower-calorie diet and exercise enough to burn about 2,800 calories a week. That translates into walking four miles a day.

If you try a low-carb diet, rely on unsaturated instead of saturated fats. Start with a palm-sized serving of low-fat protein (like poultry, seafood, or soy) and fill up the rest of your plate with fruits and vegetables plus a modest amount of nuts, avocado, or oil (to saute vegetables, dress salads, etc.).

(1) IARC Handbooks of Cancer Prevention. VoL 6. Weight control and physical activity. Lyons, France: International Agency for Research on Cancer, 2002.

(2) Lancet Oncol. 3: 565, 2002.

(3) New Eng. J. Med. 348:1623, 1625, 2003.
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Title Annotation:side effects of obesity
Author:Liebman, Bonnie
Publication:Nutrition Action Healthletter
Geographic Code:1USA
Date:Oct 1, 2003
Words:3012
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