Lifestyle decisions that may stave off onset of cancer

Personal choices, such as smoking and consumption of fatty foods, have long been linked to increased cancer risk. During recent years, scientists have been seeking to isolate a variety of lifestyle decisions that may stave off the onset of cancer or even reduce tumor formation in their early stages.

The latest round of such studies, presented at the American Association for Cancer Research's Frontiers in Cancer Prevention Research Meeting, include the impact of exercise on colon cancer in men, how aspirin consumption may negate the harmful effects of eating flame-broiled meat, and a new link between child bearing and lung cancer.

Effect of a 12-month exercise intervention on apoptosis in colon crypts: a randomized controlled trial

Exercising six days a week reduces the risk of colon cancer in men, according to a study by the Fred Hutchinson Cancer Research Center in Seattle. The study, conducted by Kristin Campbell, Ph.D., postdoctoral fellow, Public Health Sciences, and her colleagues, illustrated the role of exercise in controlling abnormal cell growth in colon tissue.

In men who engaged in moderate to vigorous exercise (an hour a day, six days a week) for a year, more apoptosis (normal cell life and death cycles) was seen in crypt cells in the colon. These cells are indentations in the colon wall and are the wellspring of polyps and other abnormal growths that can result in colon cancer. A protein called bax that promotes apoptosis was seen in higher amounts in the crypt cells among male exercisers. No such differences were seen in women, regardless of their exercise routines. But some changes in apoptosis were seen even among men who exercised less, about four times a week.

"We saw a substantial increase in the potential for cellular apoptosis in areas of the colon most vulnerable to colon cancer," said Campbell. "The increase was most pronounced in men who exercised six hours a week. No change was seen in women, a finding that is consistent with our previous findings of altered proliferation in men, but not women. Therefore, physical activity may play a stronger role in colon cancer risk reduction among men than it does among women."

The researchers examined 101 men and 98 women in one of the first randomized clinical trials to test the effect of exercise on colon cancer. The participants either exercised or maintained their usual non-active lifestyle for one year. At the same time, researchers measured apoptosis by measuring the ratio of bax, the apoptosis promoter protein, to bcl-2, an anti-apoptotic protein. The researchers also determined where in the colon-crypt cells these apoptotic changes were occurring.

Cellular proliferation in the bottom of colon crypt cells is normal. But precancerous polyps (and ultimately, cancer) can develop when the crypt's cells proliferate too quickly. In that case, cells growing too fast creep up from the bottom and spill over the upper sides, resulting in the growths seen in cancer and its predecessors. The researchers previously found lower proliferation on the upper portions of crypt cells in exercising men, while no decreases were found in women or men who did not exercise.

Is the association between flame-broiled food, meat consumption, and breast cancer modified by N-acetytransferases and aspirin use?

By studying the eating patterns of 312 women with breast cancer and 316 who were cancer free in a prospective study, Kala Visvanathan, M.B.B.S., assistant professor of epidemiology at Johns Hopkins University, and colleagues found that women who eat flame-broiled foods more that twice a month may be at increased risk of breast cancer when compared to women who don't usually eat foods prepared that way.

The good news, however, is that taking aspirin negated the potentially harmful effects.

"We are not certain of the mechanism by which aspirin may be helping attenuate these risks. This is an area that further study should elucidate as we search for means to reduce the risk of breast cancer," said Visvanathan.

The researchers first sought to determine if differences in a women's ability to activate the cancer-provoking chemicals in flame-broiled meat, known as heterocyclic amines (HCAs), modified the risk of developing breast cancer.

The NAT2 enzyme, short for N-acteyltransferase, is involved with activating heterocyclic amines. Several genes control NAT2's ability to activate HCAs: slow NAT2 metabolizers tend to produce less active HCAs than fast NAT2 metabolizers. The study found that fast metabolizers who ate more flame-broiled food were more likely to develop breast cancer than slow metabolizers who never ate such food.

"Previous work examining the association between NAT2, flame-broiled food, and breast cancer risk has been inconsistent. We find the relationship between aspirin, flame-broiled food consumption and NAT2 activity intriguing," said Visvanathan.

Nonsteroidal anti-inflammatory drugs and breast cancer risk: the multiethnic cohort

Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) had little effect on reducing the risk of breast cancer overall; however, the risk was notably lower among African-American and Caucasian women with long-term use, according to a study by the University of Hawaii and University of Southern California.

The researchers' work is one of the first to explore the relationship between COX-2 inhibitors (aspirin and NSAIDs) and breast cancer in a multiethnic population. The National Cancer Institute is currently studying COX-2 drugs (short for cyclooxygenease-2) for its effect on breast cancer. The COX-2 enzyme is activated in response to inflammation and precancerous and cancerous tissues, and its inhibition has been associated with significant reduction in breast cancer tissue. A few large research studies have also shown a reduction in risk of breast cancer among NSAID users.

While COX-2 research has found a promising association with NSAIDs and cancer, Jasmeet Gill, Ph.D., postdoctoral fellow in the Department of Etiology, and her colleagues found no associations between aspirin and other NSAID (ibuprofen, naproxen, indomethacin, etc) use and breast cancer risk, even if the women's total NSAID use (aspirin plus other NSAIDs) was for 11 or more years. There were two exceptions: African-American women cut their breast cancer risk by more than half if they took NSAIDs other than aspirin for 6 or more years, and Caucasian women likewise cut their cancer risk by 30 percent.

"The COX-2 research and the NSAID studies led us to consider whether anti-inflammatory drugs might have different associations with breast cancer risk across ethnic groups," said Gill. "We are not sure why we didn't see a reduction in breast cancer incidence for aspirin users as other studies have shown, but we are intrigued by the reduced risk we observed among African-American and Caucasian women who used other NSAIDs. We believe more studies with detailed dosage information need to be conducted to resolve the role aspirin and NSAIDs play in the inhibition of breast cancer development." Gill cautioned that their study did not collect information on dose and frequency of aspirin or other NSAID use.

The researchers followed a cohort of 99,553 African-American, Caucasian, Japanese, native Hawaiian and Latina women from Hawaii and Los Angeles County between 1993 and 2002. When examining the risk of breast cancer from aspirin and other anti-inflammatory drugs, they found that body mass, tumor stage, or age had no consistent effect on the NSAID-cancer association.

Parity and risk of lung cancer

Women's reproductive behavior (having children or not) may increase their risk of lung cancer later in life, a study at the Harvard School of Public Health has found.

Jessica Paulus, a graduate student in epidemiology, and her colleagues studied data from 1,075 women with lung cancer and 867 cancer-free women who took part in a research study from 1992 to 2004 at the Massachusetts General Hospital in Boston. The researchers found that women who had any children (one or more) had nearly 40 percent less risk of lung cancer as compared to women without children. That risk of lung cancer also declined in a linear fashion with increasing numbers of children born.

"Patterns of lung cancer incidence suggest that women may be at a greater risk of lung cancer as compared to men," said Paulus. "Given the role of estrogen as a risk factor in other cancers, and the relationship between number of births and estrogen levels in the body, we hypothesized that having children may be associated with lung cancer risk in women."

While the researchers found a linear relationship between lung cancer and number of children, having one child did not significantly decrease the cancer risk compared to women who never had given birth. Having two children reduced the risk of cancer by 20 percent, and having three or more children reduced that risk by 40 percent.

The protective effect of childbearing was strongest -- but not significant statistically -- in women who had never smoked as compared to current and former smokers. Also, the protective effect of childbearing on lung cancer risk was limited to cases of average age of onset, and was not observed in women diagnosed with lung cancer before age 55 years.

"Our study supports the idea of an inverse relationship between having children and the risk of lung cancer among women," Paulus said. "While smoking behavior remains the strongest risk factor for lung cancer in women, our work indicates a need to further examine the role played by reproductive factors in lung cancer."

Risk factors for renal cell carcinoma in the multiethnic cohort study

Moderate alcohol consumption may lower the risk of renal cell carcinoma, but only in men, while exercise may also reduce risk, but only in women.

Renal cell carcinoma, the most common malignant kidney tumor, has no known cause but has been associated with a number of risk factors. A study by the universities of Southern California and Hawaii found that risks of renal cell carcinoma rise sharply with being overweight, smoking or hypertension, and decrease with physical activity and moderate alcohol consumption.

Wendy Setiawan, Ph.D., assistant professor of preventive medicine at USC, and her colleagues studied data from 167,200 ethnically diverse Americans who had participated in a study from 1993 to 1996. During an eight-year follow-up period, the researchers found 246 men and 129 women who were diagnosed with renal cell carcinoma.

"By examining the association between body size, physical activity, smoking, alcohol consumption and medical conditions, we discovered that body mass index (BMI) increases risk, smoking and hypertension had independently higher risks of cancer, while physical activity and drinking appeared to reduce the risks," Setiawan said. "While smoking has long been associated with the cancer, some of the other risk factors are newly found associations and merit further study in preventing the disease."

The risk of renal cell cancer increased incrementally with every rising unit of BMI (measured as weight divided by height squared), especially among women. Being obese with a BMI over 30 posed a 1.5 times higher risk of cancer for men, and more than 2 and a third times higher risk for women. Hypertension increased the risk by one-and-a-half times for men and more than one-and-two-third times for women. Cigarette smoking, long considered a risk factor, was confirmed by the study.

Increased alcohol consumption, however, reduced the risk by about one-third, but only among men. In addition, physical activity reduced risk only among women.

Renal cell carcinoma, marked by the growth of malignant tumors in the lining of the kidney's tubules (which carry urine and other wastes from the blood into the bladder), constitutes 90 percent of all malignant kidney cancers. About 38,900 Americans are diagnosed with the disease each year; of that, about 12,800 die. Its occurrence is increasing by about 1.5 percent each year. The cause of the disease, as well as of its increased occurrence, remains a mystery.

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