Nov. 16, 2006 With cancer, researchers don't believe "you are what you eat"; that disease is always a direct result of what is, or what isn't, on your dinner plate. But studies into the association between diet and cancer show that food can have an impact in preventing cancer, or in reducing the aggressiveness of the disease.
At the American Association for Cancer Research's Frontiers in Cancer Prevention Research meeting, investigators have found that eating fish regularly as an adult, or soy as a young girl, or using a specific vitamin if you are a smoker, can help to protect against development of certain cancers. Another study found that blood cholesterol, some of which comes from eating animal fats, doesn't control whether a man develops prostate cancer, but lower levels of these lipids may help protect against aggressive forms of the disease. The researchers say these studies provide some of the strongest links found to date between diet and cancer.
Childhood soy intake and breast cancer risk in Asian-American women
In a novel study of Asian-American women, a team of researchers led by National Cancer Institute (NCI) investigators has found that consuming soy during childhood, adolescence and adult life were each associated with a decreased risk of breast cancer, but that the strongest and most consistent effect was seen for childhood intake.
They found that women who ate the most soy-based foods (such as tofu, miso, natto) during ages 5-11 reduced their risk of developing breast cancer by 58 percent, compared to women who ate the least amount. The corresponding reductions for adolescent and adult intake were about 25 percent.
"Childhood soy intake was significantly associated with reduced breast cancer risk in our study, suggesting that the timing of soy intake may be especially critical," said the study's lead investigator, Larissa Korde, M.D., MPH, a staff clinician at the NCI's Clinical Genetics Branch, in the Division of Cancer Epidemiology and Prevention. Korde worked in collaboration with epidemiologists at the University of Hawaii, the Northern California Cancer Center, and the University of Southern California.
The underlying mechanism is not known. However, Korde said that one hypothesis for the decreased risk associated with childhood intake is that soy isoflavones have estrogenic effects that cause changes in breast tissue, leading to decreased sensitivity to carcinogens. A similar protective effect has been found in studies of overweight girls, perhaps because fat tissue also secretes estrogens, she added.
"Hormonal exposures in adulthood, such as use of estrogen and progesterone replacement therapy, are established breast cancer risk factors. However, a growing body of evidence suggests that hormonally related exposures early in life may also modify susceptibility to breast cancer," Korde said.
Studies investigating adult soy intake and breast cancer risk have had mixed results, but the two studies that looked at adolescent consumption found that the risks of developing breast cancer later in life were cut in half. This study is the first to address the relationship between soy consumption during childhood and future risk of breast cancer.
As provocative as the findings are, the senior investigator on the study, Regina Ziegler, Ph.D, MPH, cautioned that it would be premature to recommend changes in childhood diet. "This is the first study to evaluate childhood soy intake and subsequent breast cancer risk, and this one result is not enough for a public health recommendation," she said. "The findings need to be replicated through additional research."
The researchers conducted a case-control study of women of Chinese, Japanese and Filipino descent who were living in the San Francisco Bay area, Los Angeles, or Oahu, Hawaii. Included were 597 Asian-American women with breast cancer and 966 women without the disease, who answered questions about their adult and adolescent diet and lifestyle. In addition, for a subset of 255 participants whose mothers were alive and living in the US, the mothers were asked about their daughter's early childhood exposures.
Soy intake was then divided into thirds, based on frequency of consumption, and by comparing the highest category to the lowest, the researchers found an inverse association between the risk of developing breast cancer and the amount of soy consumed. The childhood relationship held in all three races and all three study sites, and in women with and without a family history of breast cancer. Since the effects of childhood soy could not be explained by other measures of Asian lifestyle during childhood or adult life, researchers concluded that early soy intake might itself be protective.
A prospective study of fish, n-3 fatty acid intake, and colorectal cancer risk in men
Men who ate fish five times a week or more had a 40 percent lower risk of developing colorectal cancer compared to men who ate fish less than once a week, according to a new analysis of data from 22,071 participants in the Physicians' Health Study (PHS).
The researchers say the reduction in colorectal cancer risk is substantial in comparison to other dietary components, and while they don't suggest that everyone starts eating fish daily simply because of these results, they say the health benefits of fish consumption have already been proven.
"We already know that eating fish can reduce the risk of sudden cardiac death, and this might provide another reason to add fish to your diet," said Megan Phillips, a doctoral student at the Harvard School of Public Health and the lead author of this study.
The researchers believe the health effects of fish consumption in relation to colorectal cancer may lie in their content of the n-3 fatty acids that can inhibit the cyclooxygenase-2 (COX-2) enzyme. This enzyme acts as a mediator of inflammatory responses thought to be associated with cancer development.
The PHS was designed as a randomized, double blind, placebo-controlled clinical trial to examine the effect of aspirin and beta-carotene supplements on development of cancer and cardiovascular disease, and the participants filled out a one-time food questionnaire 12 months after starting the study. In this analysis, investigators were also trying to determine if fish consumption had a different effect on men who received aspirin for five years compared to men who weren't randomized to use aspirin, which is also a COX-2 inhibitor. "We thought that maybe for men who received aspirin, it wouldn't matter whether they ate fish or not," Phillips said.
The researchers looked at four different categories of fish consumed- tuna fish, dark meat fish (salmon, sardines, bluefish, etc.), a general fish category, and shellfish including shrimp, lobster and scallops- and asked how many times the participants ate them on average during the previous year. They found almost 10 percent ate fish less than once a week, 31 percent ate it less than two times a week, 48 percent ate fish less than five times a week, and about 11 percent ate it five times or more a week. They then compared these figures with incidence of colorectal cancer that later developed in the men. (The average follow-up was 19.4 years).
They found that compared to men who ate the least amount of fish, the risk of developing colorectal cancer was 40 percent lower in men who ate the most fish, was 20 percent lower in men who ate fish 2-5 times a week, and 13 percent lower among participants who ate fish less than two times a week.
The relationship between fish consumption and colorectal cancer was similar for men randomized to aspirin and those who weren't, possibly because the researchers only had information on aspirin use during the first five years in the trial, and "it may take more years of aspirin use to see an effect," Phillips said.
While she said the results are promising, Phillips also noted that they are based on the assumptions that the pattern of fish consumption observed in the sole food questionnaire represented a diet that the men subsequently followed for many years.
In addition, men who consumed more fish may also have a healthier lifestyle perhaps including better cancer screening. Although this study controlled for some of these factors such as cigarette smoking, vigorous exercise, and multivitamin use, the investigators do not have information on colorectal endoscopies. Thus, these findings need additional confirmation through other prospective studies with more complete information and a definitive answer might require a randomized trial, said senior author Jing Ma, M.D., Ph.D., a researcher at the Brigham and Women's Hospital-based Channing Laboratory and associate professor of medicine at Harvard Medical School.
The relationship between dietary antioxidants and oxidative damage in smokers: evidence of effect modification by lifestyle and genetic factors
Vitamin E in the diet of male smokers appears to protect against oxidative damage that can lead to cancer development, according to researchers from Columbia University's Mailman School of Public Health working with investigators from the NYU School of Medicine.
They found that male smokers who had high plasma levels of vitamin E had lower levels of oxidative-DNA damage in their white blood cells. Oxidative DNA damage is a mechanism by which tobacco smoking can increase risk of cancer. In addition, the protective effect of vitamin E was greatest among the men with a beneficial form of a common "detoxifying" gene, GSTM1. The investigators did not find a similar effect of vitamin E in women.
"There was a dose-response relationship, in that the more vitamin E we found in the blood of the men, the less there was of this cancer-related biomarker," said the study's senior investigator, Frederica P. Perera, Dr.P.H., Professor in the Division of Environmental Health Sciences at the Columbia University School of Public Health.
"This suggests that while working toward the goal of quitting smoking, which is the very best way to prevent development of smoking-related cancers, it could be helpful to eat a diet rich in vitamin E," she said, and added, "we don't yet know why this relationship was not found in women, but a good diet is beneficial to health in many ways."
The most active form of vitamin E (known as alpha-tocopherol) is believed to be a strong antioxidant, capable of preventing oxidative chemical reactions that damage DNA. The vitamin is found in certain vegetable oils, nuts, whole grains, fish, green leafy vegetables and other foods. Studies that have examined the ability of vitamin E to protect against cancer have shown mixed results, however.
The present study is unusual, the researchers say, because it measured two different markers in white blood cells drawn from 280 participants - people who smoked at least 10 cigarettes a day. These markers were the amount of vitamin E in blood derived from food (those who used vitamins were excluded from this study) and the quantity of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a measure of oxidative damage to DNA.
The researchers found a protective effect of plasma alpha-tocopherol on oxidative damage among smokers, but only among men. They next looked at the interaction between vitamin E and GSTM1, a gene variant known to produce enzymes that efficiently detoxify carcinogens in tobacco smoke, and found a greater effect of the vitamin among men with this gene.
"We all want to know if vitamins help protect us against disease, and measuring their effects in the blood using markers of cellular damage is the most direct way to do that," said Perera. "But we have a lot of work ahead before we can fully understand the role of antioxidants in the chemoprevention of tobacco-related cancer."
Association between plasma cholesterol and prostate cancer
Prostate cancer patients who had lower levels of cholesterol in their blood had a significantly reduced chance of developing more aggressive forms of the disease, compared to patients with higher cholesterol readings.
These findings may help explain the earlier discovery, reported by the same team of researchers at the AACR annual meeting in 2005, that men who used statin drugs experienced half the risk of developing advanced prostate cancer.
"Statin drugs reduce cholesterol in the blood, but they also influence a number of different pathways," said the study's lead researcher, Elizabeth Platz, ScD, MPH, an associate professor in the Department of Epidemiology at Johns Hopkins Bloomberg School of Public Health. "This study suggests that the ability of statins to lower cholesterol may be important to prostate carcinogenesis, but we are continuing to examine other pathways with which statin drugs interact, such as reduction of inflammation."
The researchers looked at cholesterol levels first because cholesterol affects cell signaling and survival. Some scientists theorize that a large quantity of cholesterol in the blood could stimulate the survival of abnormal prostate cells.
They studied blood drawn from 698 men before they were diagnosed with prostate cancer and matched it to blood taken from 698 men who had not been diagnosed with the disease. All of the men participated in Harvard University's Health Professionals Follow-up Study, a group of 18,018 participants who provided a blood sample between 1993 and 1995.
They found that mean cholesterol levels did not differ between the men with prostate cancer and the control participants, suggesting that cholesterol was not involved in the initial development of prostate cancer, Platz said.
But when comparing men who had the lowest quartile of serum cholesterol to men who had the highest, they found that prostate cancer patients with lower cholesterol had the lowest risk of developing a more worrisome form of the disease. They specifically found that the risk of being diagnosed with high-grade or advanced cancer was reduced by 40 percent and 50 percent, respectively.
Platz says it is not clear at what levels serum cholesterol may stimulate the abnormal growth seen in cancer development. "The findings suggest either that high cholesterol may push existing prostate cancer to become aggressive, or, alternatively, very low levels of cholesterol may provide protection against development of an aggressive cancer," she said. "We just don't know which it is at this point."
She also said that because the findings come from an observational study, not a trial, it is impossible to conclude that men can lower their risk of developing an aggressive form of prostate cancer by reducing their intake of saturated fat, the type of fat that increases serum cholesterol, which some studies have linked to an increased risk of advanced prostate cancer.
"It is too soon to say that such measures would be specifically beneficial to lowering such a risk, but for good health in general, it is prudent to consume a diet that contains healthful fats that do not increase serum cholesterol," she said.
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