Genetics may influence the effects of vitamin E on cancer risk

January 08, 2019

Almost half of all Americans take a vitamin supplement, and yet many large-scale, placebo-controlled clinical trials of various supplements have found little or no benefit. A new study led by investigators from Brigham and Women's Hospital suggests an intriguing reason for this: genetic variation may be influencing these effects, increasing risk in some individuals while decreasing risk for others. Investigators conducted a retrospective analysis of the Women's Health Study (WHS) and its genetic component, the Women's Genome Health Study (WGHS), as well as validated their results in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study (ATBC). Both of these trials investigated whether taking vitamin E supplements could affect risk of cancer. They found that genetic variations in the gene COMT influenced whether vitamin E decreased or increased risk of developing cancer during and after the study periods. Their results are published online in The Journal of the National Cancer Institute.

"Observational studies of people taking vitamin E have reported benefits, and studies in animal models have suggested a protective effect, but when vitamin E supplements were brought into placebo-controlled clinical trials, the results were null," said Kathryn Hall, PhD, MPH, from the Division of Preventive Medicine at the Brigham. "This made it easy to assume that vitamin E just doesn't work. But what we've found is that it may have been protective in some and not in others, and that genetic variation is linked to these outcomes."

Multiple pathways may link the enzyme catechol-O-methyltransferase (COMT) to how vitamin E is processed by the body. Hall and colleagues previously found that genetic differences in COMT modified the effects of vitamin E on cardiovascular disease risk.

The most extensively studied variant in COMT comes in three genetic "flavors": met/met, val/met and val/val. People with the val/val variant have a version of COMT that is 3-4 times more enzymatically active than people with met/met.

Hall and her co-authors, including colleagues from the Division of Preventive Medicine - Nancy Cook, ScD, Julie Buring, ScD, Howard Sesso, ScD, and Daniel Chasman, PhD - as well as Paul Ridker, MD, director of the Center for Cardiovascular Disease Prevention, looked at cancer rates among women during the WHS/WGHS trial, which lasted 10 years, plus the 10 years immediately following the trial's conclusion. They found that in the overall period, for women with the met-met variant who took vitamin E compared to placebo, rates of total cancer were 14 percent significantly lower, while they were 15 percent higher for women with the val-val variant who took vitamin E compared to placebo.

Participants in the WGHS were all female health care professionals in good health at the beginning of the trial. The researchers validated these results by looking at a second cohort. Similar results were seen in the ATBC trial, led by Demetrius Albanes, MD, MPH, of the National Institutes of Health, which included only male smokers from Finland.

The team also analyzed rates of cancer sub-types such as breast, lung, uterine and colorectal cancer, finding similar trends to the overall cancer rates.

"Significant gene-drug interactions are hard to find, and this one is particularly striking. Now we need to understand which cancers are affected, why and how, and these results encourage us to pursue this with robust and rigorous curiosity," said Hall.
-end-
Funding for this work was provided by NHLBI K01HL130625, a Harvard CATALYST faculty fellowship, and NCCIH 2K24 AT004095. The WHS is supported by grants CA047988, HL043851, HL080467, HL099355, and UM1 CA182913 from the NIH (Bethesda, MD) and a research supplement from the Office of Dietary Supplements. The ATBC Study is supported by the Intramural Research Program of the U.S. National Cancer Institute, National Institutes of Health, and by U.S. Public Health Service contract HHSN261201500005C from the National Cancer Institute, Department of Health and Human Services.

Paper cited: Hall, K et al. "COMT modifies alpha-tocopherol effects in cancer prevention: gene-supplement interactions in two randomized clinical trials" JNCI DOI: 10.1093/jnci/djy204.

Brigham and Women's Hospital

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.