Have you ever wondered why there is contradictory information about what foods we should and shouldn’t eat in order to prevent and control disease?

It turns out that each individual may have their own genetic “toolbox” of gene variants that they can use in combination with bioactive food components to prevent chronic diseases they may be at higher risk for developing. Find out how scientists are learning and applying knowledge from the new science known as “Nutrigenomics.”

A study reported in the Journal of the American Medical Association found no evidence that eating fruits and vegetables lowered the risk of breast cancer (Prentice et al. 2006). This study is in conflict with data reported from many other studies demonstrating that fruits and vegetables do have the ability to lower the risk of breast cancer.

So which study results are we to believe? One answer can be found in the relatively new science called Nutrigenomics. Nutrigenomics aims to identify the unique gene variants, that each individual has that, in combination with certain bioactive foods, may offer protection from developing specific diseases.

Dr. Ordovas, Senior Scientist, and Director of the Nutrition and Genomics Laboratory, at the U.S Department of Agriculture’s, Human Nutrition Research Center on Aging at Tufts University, is a strong example of someone that has studied Nutrigenomics.

Dr. Ordovas provided an example of how Nutrigenomics can be used to make sense of the sometimes confusing and contradictory findings in the field of nutrition (Yaktine and Pool 2007). He wanted to show what might be missing in studies like the one described above, where there was no evidence that eating fruits and vegetables lowered the risk of breast cancer.

To accomplish this, Dr. Ordovas looked at results from the Framingham Heart study, which at first glance, showed no difference in the High Density Lipid (HDL) protein levels (good cholesterol) for people who have different gene variants in one of the cholesterol transport genes, Apolipoprotein A-1 (APOA1), in their genetic toolboxes.

Dr. Ordovas hypothesized that diet might combine with an individual’s gene variant to influence their HDL level. He was right.

However, when he studied the results further, he realized that the study analysis that was conducted did not take into account the study participants’ diet. Dr. Ordovas hypothesized that diet might combine with an individual’s gene variant to influence their HDL level. He was right. When a person’s diet was taken into consideration, the data had a totally different interpretation.

Specifically, when he re-analyzed the data, Dr. Ordovas, divided the study participants’ data into groups of individuals with specific types of APOA gene variants and further broke up the groups according to how much polyunsaturated fat they had in their diet.

Then he analyzed the data and found that in each group, the HDL levels were linked to both an individual’s specific type of APOA gene variant, and the amount of polyunsaturated fat the study participant consumed in their diets.

In his results, Dr. Ordovas found that for one group of study participants that had a particular APOA gene variant, higher polyunsaturated fat levels consumed in the diet resulted in lower HDL levels.

Whereas for individuals in another group with a different APOA gene variant, consuming higher levels of polyunsaturated fats produced opposite results. Their HDL levels went up when they ate higher levels of polyunsaturated fat.

This was important data for these individuals to have because higher HDL levels are generally associated with a decreased cardiovascular disease risk.

According to Dr. Ordovas, the bottom line was:

“It was particularly important for people who had one gene variant to minimize their consumption of polyunsaturated fat in order to keep their levels of the good cholesterol as high as possible (Yaktine and Pool 2007).”

Conversely, individuals with the other APOA gene variant were able to achieve increases in good cholesterol levels by increasing their dietary intake of polyunsaturated fat (Ibid).

Dr. Ordovas stated,

“It is thus important for both doctors and researchers to take into account the genetic makeups of their patients when they try to understand and predict the effects of diet on health”(Ibid).

Future studies must be conducted to confirm these results and to see what other gene variants and environmental factors might also contribute to an individual’s HDL levels.

A second example of using our genetic toolboxes comes from Dr. Wu, at the University of Southern California’s Norris Comprehensive Cancer Center in Los Angeles, CA. Like Dr. Ordovas, Dr. Wu was interested in a bioactive food component. This time it was green tea instead of polyunsaturated fats. Dr Wu and her colleagues were interested in breast cancer prevention, in association with green tea, in women with the catechol- O-methyltransferase (COMT) gene variant. The COMT gene produces a protein, which is an enzyme that catalyzes the metabolism of tea polyphenols.

More importantly, scientists have found that there is a specific COMT gene variant that, in some people, produces a protein that has a 3-4 fold decrease in enzymatic activity. Dr. Wu and her colleagues wanted to find out what effect that gene variant might have on green tea’s ability to prevent breast cancer.

Dr. Wu and her colleagues had just finished conducting a study where they found that green tea, but not black tea, had a preventive affect against breast cancer:

“In conclusion, our study shows that green tea may act as a chemopreventive agent against breast cancer development. Confirmation of these findings is needed. We also need, in particular, a better understanding of the dose–response relationships since our findings are based on modest amounts of green tea intake” (Wu et al. 2003b).

However, the study did not look at the COMT gene variants.

Dr. Wu and her colleagues knew that other scientists thought that the lower biotransformation of the tea polyphenols (catechens), caused by the “low activity” COMT gene variant, might increase the accumulation of catechol estrogen intermediates, thereby increasing breast cancer risk. In fact, several studies had explored this question, but study results had been inconsistent (Liehr and Ricci 1996).

Dr. Wu and her colleagues decided to return to the same group of women that participated in the first experiment with green tea and conduct a second experiment to find the answer. When the second study was completed, there were surprising results. In contrast to what some scientists had previously thought, women with at least one “low activity” COMT gene variant had a significantly reduced risk for developing breast cancer that was associated with drinking either green tea or black tea (Wu et al. 2003a). Women with two alleles* of the high activity COMT gene variant did not have this breast cancer preventive effect.

Again, future studies will be required to confirm and extend these results and to determine what other factors might combine with a person’s genotype to alter breast cancer risk.

For example, the action of the COMT enzyme may change with age and gender. One scientist reported that “COMT activity in some peripheral tissues analyzed appeared to have age- and sex-related differences” (Zhu 2002) Also, Dr. Wu and her colleagues studied the COMT gene variant’s effect only in Asian women. Studies in women from different ethnic backgrounds will need to be conducted to determine if Dr. Wu and her colleagues’ results apply to them as well. Hence, there is still much to be done in order to fully understand the COMT gene and the gene variants associated with it that may, in combination with green tea, influence and individual’s risk for preventing breast cancer. Nonetheless, Dr. Wu and her colleagues’ study results help us understand the important role Nutrigenomics can play in breast cancer prevention.

In a third example of Nutrigenomics, Dr. Iman A Hakim, and her colleagues at the University of Arizona conducted a study, in collaboration with scientist at the University of Maryland and the National Institutes of Health (NIH), which also looked at the bioactive food component green tea. Specifically, they conducted a study to find out if drinking green tea could decrease the level of tobacco carcinogens in individuals who smoked cigarettes and who also had a Glutathione S-transferase gene variants in their genetic toolbox (Hakim et al. 2004).

The Glutathione S-transferase gene produces a protein that is both an antioxidant and a cytoprotective enzyme.

The two gene variants of this enzyme that Dr. Hakim and her colleagues looked at were “GSTM1” and “GSTT1.” Individuals with these two enzymes have been postulated to have more prominent GST enzyme induction (Ibid).

This increased induction of the GST enzyme, with its antioxidant and cytoprotective effects, would be especially relevant for smokers who have been found to have increased clusters of oxidized DNA base-pair damage in their stem cells (Bennett et al. 2008).

The DNA damage in these cigarette smokers involved DNA repair capacity. Specifically, scientists have found that in a highly damaging environment, DNA repair capacity can be overwhelmed, which occurs in the stem cells of cigarette smokers:

“These results suggest that levels of DNA-damaging agents in these tobacco-using (bone marrow) donors are sufficient to overwhelm cellular repair capacity, allowing the accumulation of potentially mutagenic clustered damages, even in tissue not directly exposed to tobacco constituents” (Ibid).

Hence, it is particularly important to see to what extent individuals who smoke cigarettes and possess these GST gene variants might be able to decrease DNA damage by drinking green tea.

Significantly, study results obtained by Dr. Hakim and her colleagues demonstrated that there was a statistically significant decrease in DNA damage in smokers with these gene variants that drank four 8 ounce cups of green tea per day over a four month period. These results were in comparison to cigarette smokers that participated in the study, did not have these gene variants, and drank the same quantity of green tea during the 4 month study period (Hakim et al. 2004).

DNA damage is generally considered a necessary step in cancer initiation, so studying ways to decrease DNA damage should enable scientists to make important headway into preventing cancer. New knowledge about how GST gene variants, in combination with green tea, may have the ability to decrease DNA damage in cigarette smokers. This offers exciting new information for cancer prevention knowledge that is based on Nutrigenomics.

Dr. Hakim noted that further studies are necessary to understand the interaction between green tea consumption and the GST genotypes* in relation to smoking-induced oxidative DNA damage.

DNAScribe will continue to report on the work that scientists are conducting in Nutrigenomics and it will let you know about new studies that are being conducted in this area that you may want to participate in.