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How good fats, bad fats and other dietary patterns may influence risk for cancer

American Association For Cancer Research (AACR) : 06 July, 2006  (Technical Article)
Though scientists have long suspected that diet and obesity play a significant role in cancer risk, the latest results are suggesting the problem may be more serious than previously thought. Updated population studies suggest that the projected burden of cancer resulting from overweight and obesity may thwart other efforts to reduce cancer incidence over the next couple of decades, including curtailment of smoking.
Poor eating patterns, generally referred to as the 'Western diet,' may contribute to increased incidence of breast cancer among African-American women, according to a large study presented at this meeting.

On the other hand, consumption of fatty oils from other sources, including fish, flaxseed, corn and vegetable oils, may prove to be beneficial for some, perhaps depending on an individual's genetic makeup.

Results from these studies, summarized below, will be presented this week during the AACR International Conference on Frontiers in Cancer Prevention Research.

Updated evidence on the proportion of cancer due to obesity (Abstract 3513)

Growing evidence suggests that overall cancer incidence and mortality resulting from overweight and obesity is increasing, potentially thwarting other prevention and treatment efforts aimed at reducing these dire statistics.

'Given the trends in obesity and the increasing evidence of a broad range of cancers caused by excess energy balance, the projected burden of cancer over the coming years is worrisome,' according to Graham Colditz, professor of epidemiology with the Harvard School of Public Health.

The latest projections represent a departure from an earlier report prepared in 2002 by the International Agency for Research on Cancer Committee on Weight Control and Physical Activity, based on European estimates for cancer prevalence.

That report concluded that overweight and obesity are related to cancers of the colon, endometrium, kidney and esophagus, as well as postmenopausal breast cancer. The study was based on estimates that 50 percent of all men, and 35 percent of all women were overweight, with 13 percent of men and 19 percent of women classified as obese.

The new projections stem from a review of published studies, updates to the IARC report from 2002, and data from the Nurses' Health Study II, which includes 116,686 women.

'Given the trend to increasing prevalence of obesity, these estimates are conservative,' Colditz said.

Furthermore, he said that scientists now recognize a broader range of cancers associated with cancer mortality. These include myeloma, lymphoma and pancreatic cancers. Other sites are under review.

'The epidemic of obesity will run counter to the improving trends, such as a decrease in current smoking, that may suggest the incidence of cancer can be reduced,' said Colditz.

'Western' diet increases breast cancer risk among African-American women
(Abstract 2640)

African-American women who eat more foods from what many refer to as a typical 'Western' diet appeared more than twice as likely to get breast cancer in their lifetimes than others who consume far less, according to a study of individuals participating in the Black Women's Health Study.

As described by the study, the 'Western' diet is characterized by higher intakes of refined grains, red meat, processed meat, high fat dairy, eggs, fries, sweets, soda and snacks.

By contrast, those who consume far more foods from a so-called 'prudent' diet appeared to have a decreased risk of developing breast cancer. The 'prudent' diet features higher intakes of cruciferous vegetables, other vegetables, fruits, whole grain, cereals, fish, poultry and beans.

The study involved a self-reported questionnaire of dietary patterns and other potential risk factors for breast cancer among 57,877 women. Between 1995 and 2003, some 816 women in the study group were diagnosed with breast cancer.

As such, it represents the largest yet to study the relationship between diet and breast cancer among African-American women.

'Epidemiological studies have been inconsistent in supporting a role of dietary patterns in breast cancer risk,' said Tanya Agurs-Collins, Ph.D., R.D., program director with the Health Promotion Research Branch of the National Cancer Institute, and the study's lead investigator. 'Our results suggest that an overall healthy diet can decrease one's risk from breast cancer. Should these results be confirmed, the public health implications are that women can decrease their risk from breast cancer by consuming a healthy diet that is high in fruits and vegetables, low in fat, and by avoiding obesity.'

After adjusting for breast cancer risk factors -- such as age, smoking, education, alcohol, family history, age of first birth, body mass index, exercise, and energy intake, the scientists concluded that those individuals in the highest tertile of the 'prudent' diet, those who ate the highest amount of foods from this diet, appeared to have a decreased risk for developing breast cancer.

Interestingly, when stratified on body mass index, women who consumed the most foods from the 'prudent diet' and were not obese had the greatest protection from breast cancer.

Fish oil slows growth of colon polyps in laboratory mice (Abstract 3716)

The protective effect of fish oils, called marine n-3 or omega-3 fatty acids, may be extended to colon cancer, according to animal studies conducted by researchers at the Vanderbilt-Ingram Cancer Center in Nashville, Tenn.

Their results showed that colon polyps were generally smaller among laboratory mice fed a diet rich in fish oil compared to other mice on a high-fat diet. Specifically, the scientists found that half the mice on the high fat diet had polyps greater than 2 millimeters in size, compared to only 18 percent of mice on the fish oil diet.

Upon closer inspection, the scientists found that the fish oil diet resulted in a four-fold increase in polyunsaturated fats and a decrease in other lipids in the intestinal tracts of these specially bred animals called Min (for multiple intestinal neoplasia) mice, used to study early-stage colon tumor progression.

'Our hypothesis is that a PUFA, or a pattern of PUFAs, contributes to slowing the growth of polyps that sporadically arise in this mouse model of colon cancer,' said J. Oliver McIntyre, a research professor at Vanderbilt. 'This needs to be tested by further experiments.

For their experiment, the scientists employed a relatively new analytical approach called 'computational lipidomics,' which compares hundreds of lipids from two different populations, such as polyps and normal tissue, using mass spectrometry and computer algorithms.

Future work will focus on the molecular mechanisms that are triggering, in animals on a diet rich in fish oil, the reduced growth of colonic polyps seen in these series of experiments.

'At this stage, our work is basic science, though we expect that our kind of approach will be useful in identifying targets for prevention, whether through lifestyle factors of chemoprevention and that it will have some relevance in the future for people interested in reducing their risk from colon cancer,' said McIntyre.

Consumption of omega-6 fatty acids may lower risk of prostate cancer (Abstract 3472)

In the largest study of its kind to date, a team led by scientists at the Harvard School of Public Health has found that omega-6 fatty acids typically found in salad dressings, corn and other non-hydrogenated vegetable oils may actually offer some protection against prostate cancer.

The 13-year prospective study, involving U.S. physicians from The Physician's Health Study, found that men with the highest blood levels of linoleic acid, the major omega-6 fatty acid in non-hydrogenated vegetable oils, were 40 percent less likely to get prostate cancer as those with the lowest level of this fatty acid in their blood.

The study results confirm the findings of some smaller European studies, but also differ from others that have suggested the opposite conclusion.

'This study is the largest one conducted to date exploring the association between biomarkers of fatty acid intake and risk of prostate cancer,' said Jorge E. Chavarro, a doctoral candidate in the departments of Nutrition and Epidemiology at the Harvard School of Public Health, and the study's lead investigator.

'If the findings are confirmed, the implications are that intake of linoleic acid is not harmful to the prostate and may actually be beneficial to help lower the risk of prostate cancer,' he added.

To conduct the study, the scientists analyzed blood collected and frozen in 1982 as part of the Physician's Health Study, which involved 14,916 U.S. physicians. Omega-6 fatty acid levels as a percentage of all fatty acids were determined for 479 individuals from this group diagnosed with prostate cancer through 1995, along with 491 matched controls.

While higher blood levels of linolic acid were associated with reduced risk from prostate cancer, several other fatty acids including gamma linolenic acid and dihomo gamma linolenic acid, along with arachidonic acid, were linked to an increased risk.

'Blood levels of linoleic acids are a good biomarker of linoleic acid intake, mostly intake of salad dressings and non-hydrogenated vegetable oils,' said Chavarro. 'Thus our results suggest that intake of linoleic acid may reduce the risk of prostate cancer.

'On the other hand, blood levels of GLA, DHGLA and AA are not good biomarkers of intake of these fatty acids. The blood levels of these fatty acids most likely represent the activity of the enzymes that metabolize these fatty acids, not diet.'

Future research will focus on clarifying the role of omega-6 fatty acids in prostate cancer, and to determine if some other dietary or behavioral factor may also be contributing to the results seen in this study.

Potential Cancer Preventative Benefits of Flaxseed Depends on Genetic Makeup of the Individual (Abstract 3664)

Dietary flaxseed and its components have been shown to reduce the levels of sex hormones associated with breast cancer in animal studies and among postmenopausal women. But studies now suggest that flaxseed might be more beneficial to women with a particular genetic makeup.

In this case, the scientists focused on variations in two key genes responsible for the conversion of estrogen to specific metabolites. 'This is likely a partial explanation for why not everyone who is exposed to something, such as diet, may have a good or bad result from it,' said Susan McCann, with Cancer Prevention and Population Studies at the Roswell Park Cancer Institute, Buffalo, N.Y.

In their study, the scientists examined how variants in the two genes, COMT and CYP1B1, affected estrogen metabolism from flaxseed consumption among 132 healthy, postmenopausal women aged 46 to 75 years. Participants consumed 10 grams of ground flaxseed daily for seven days, with no other dietary changes. Flaxseed is an excellent dietary source for substances called lignans, classified as phytoestrogens (plant estrogens) because they seem to mimic the action of estrogen in animals.

In previous studies, flaxseed consumption was shown to result in higher conversion of estrogen to a metabolite called 2-hydroxyestrone, which has been linked to lower breast cancer risk in animal and human studies. The new results successfully replicated these findings, in addition to showing that flaxseed consumption results in a higher ratio of 2-hydroxyestrone to another estrogen metabolite called 16-hydroxyestrone.

However, the findings also revealed that women with specific variants in these two genes converted more estrogen to the relevant metabolites than those women with two common genes. In the study group, about 28 percent of the women had two variants for COMT, while 16 percent had variants for CYP1B1.

'One should keep in mind that we only examined two genes,' said McCann. 'The body has a number of complementary pathways, so that if one pathway doesn't work well, another one can take its place.

'Our results are one more piece in the diet and cancer prevention puzzle. Potentially, we may, in the future, be able to target specific interventions to those people most likely to benefit.'
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