Can A Diet Low In Carbs & High On Protein Help In the Fight Against Cancer?

Eating a low-carbohydrate, high-protein diet may reduce the risk of cancer and slow the growth of tumors already present, according to a study published in Cancer Research, a journal of the American Association for Cancer Research.

Gerald Krystal, Ph.D., Professor, Pathology & Laboratory Medicine, University of British Columbia; Distinguished Scientist, Terry Fox Laboratory, British Columbia Cancer Agency

Eating a low-carbohydrate, high-protein diet may reduce the risk of cancer and slow the growth of tumors already present, according to a study published in Cancer Research, a journal of the American Association for Cancer Research.

The study was conducted in mice, but the scientists involved agree that the strong biological findings are definitive enough that an effect in humans can be considered.

“This shows that something as simple as a change in diet can have an impact on cancer risk,” said lead researcher Gerald Krystal, Ph.D., a distinguished scientist at the British Columbia Cancer Research Centre.

Cancer Research editor-in-chief George Prendergast, Ph.D., CEO of the Lankenau Institute for Medical Research, agreed. “Many cancer patients are interested in making changes in areas that they can control, and this study definitely lends credence to the idea that a change in diet can be beneficial,” said Prendergast, who was not involved with the study.

Krystal and his colleagues implanted various strains of mice with human tumor cells or with mouse tumor cells and assigned them to one of two diets. The first diet, a typical Western diet, contained about 55 percent carbohydrate, 23 percent protein and 22 percent fat. The second, which is somewhat like a South Beach diet but higher in protein, contained 15 percent carbohydrate, 58 percent protein and 26 percent fat. They found that the tumor cells grew consistently slower on the second diet.

As well, mice genetically predisposed to breast cancer were put on these two diets and almost half of them on the Western diet developed breast cancer within their first year of life while none on the low-carbohydrate, high-protein diet did. Interestingly, only one on the Western diet reached a normal life span (approximately 2 years), with 70 percent of them dying from cancer while only 30 percent of those on the low-carbohydrate diet developed cancer and more than half these mice reached or exceeded their normal life span.

Krystal and colleagues also tested the effect of mTOR inhibitor CCI-779 (temsirolimus/Torisel®), which inhibits cell growth, and COX-2 inhibitor celecoxib (Celebrex®), which reduces inflammation, on tumor development, and found these agents had an additive effect in the mice fed the low-carbohydrate, high-protein diet.

When asked to speculate on the biological mechanism, Krystal said that tumor cells, unlike normal cells, need significantly more glucose to grow and thrive. Restricting carbohydrate intake can significantly limit blood glucose and insulin, a hormone that has been shown in many independent studies to promote tumor growth in both humans and mice.

Furthermore, a low-carbohydrate, high-protein diet has the potential to both boost the ability of the immune system to kill cancer cells and prevent obesity, which leads to chronic inflammation and cancer.

About the American Association For Cancer Research (AACR)

The mission of the AACR is to prevent and cure cancer. Founded in 1907, the AACR is the world’s oldest and largest professional organization dedicated to advancing cancer research. The membership includes 33,000 basic, translational and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 90 other countries. The AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants, research fellowships and career development awards. The AACR Annual Meeting attracts more than 18,000 participants who share the latest discoveries and developments in the field. Special conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment and patient care. Including Cancer Discovery, the AACR publishes seven major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; Cancer Epidemiology, Biomarkers & Prevention; and Cancer Prevention Research. AACR journals represented 20 percent of the market share of total citations in 2009. The AACR also publishes CR, a magazine for cancer survivors and their families, patient advocates, physicians and scientists.

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One In Three Billion Found: Single Mutation In FOXL2 Gene May Cause Granulosa Cell Ovarian Cancer

“… Vancouver scientists from the Ovarian Cancer Research (OvCaRe) Program at BC Cancer Agency and Vancouver Coastal Health Research Institute have discovered that there appears to be a single spelling mistake in the genetic code of granulosa cell tumours, a rare and often untreatable form of ovarian cancer. This means that out of the three billion nucleotide pairs that make up the genetic code of the tumour, one – the same one in every tumour sample – is incorrect. The discovery, published online June 10th in the New England Journal of Medicine, marks the beginning of a new era of cancer genomics, where the complete genetic sequence of cancers can be unravelled and the mutations that cause them exposed. For women with granulosa cell tumours it represents the first specific diagnostic tool and clear path to develop much needed treatments for this cancer. …”

Found: One in Three Billion

The spelling mistake in the genetic code that causes a type of Ovarian Cancer

Eureka! Vancouver scientists from the Ovarian Cancer Research (OvCaRe) Program at BC Cancer Agency and Vancouver Coastal Health Research Institute have discovered that there appears to be a single spelling mistake in the genetic code of granulosa cell tumours, a rare and often untreatable form of ovarian cancer. This means that out of the three billion nucleotide pairs that make up the genetic code of the tumour, one – the same one in every tumour sample – is incorrect. The discovery, published online June 10th in the New England Journal of Medicine, marks the beginning of a new era of cancer genomics, where the complete genetic sequence of cancers can be unravelled and the mutations that cause them exposed. For women with granulosa cell tumours it represents the first specific diagnostic tool and clear path to develop much needed treatments for this cancer.

Dr. David Huntsman

David Huntsman, M.D. (Nfld.), Associate Professor, Department of Pathology & Laboratory Medicine, University of British Columbia; Genetic Pathologist, BC Cancer Agency

“This is really a two-fold discovery,” says Dr. David Huntsman, lead author and genetic pathologist at the BC Cancer Agency and Vancouver General Hospital and associate professor in the Department of Pathology and Laboratory Medicine at the University of British Columbia. “It clearly shows the power of the new generation of DNA sequencing technologies to impact clinical medicine, and for those of us in the area of ovarian cancer research and care, by identifying the singular mutation that causes granulosa cell tumours, we can now more easily identify them and develop news ways to treat them.”

In the past when scientists wanted to look at the sequence of a tumour, it was a laborious process, with each gene individually decoded into thousands of nucleotides and all data accumulated and sorted. Most studies could only look at one or at most a few of the 20,000 genes in the human genome whereas the new sequencing technologies allow scientists to look at everything at once. Through a collaboration between OvCaRe and the BC Cancer Agency’s Genome Sciences Centre, the research team used “next generation” sequencing machines that are able to decode billions of nucleotides at rapid speed and new computer techniques to quickly assemble the data. “This task would have been unfathomable in terms of both cost and complexity even two years ago,” says Dr. Marco Marra, Director of the BC Cancer Agency’s Genome Sciences Centre.

The OvCaRe team decoded four tumour samples of the relatively rare granulosa cell tumour, which affects five percent of ovarian cancer patients. Using the new sequencing technology and bioinformatics, they discovered a single nucleotide located in the FOXL2 gene was mutated in every sample. The research team further validated their work by examining a large number [95 samples] of additional tumour samples from across Canada and around the world, and are satisfied they have been able to validate that this mutation is present in almost all granulosa cell tumours and not in unrelated cancers. Most types of cancers, including ovarian cancers, have a broad range of genetic abnormalities. This finding shows that granulosa cell tumours have a characteristic single DNA spelling mistake that can serve as an easy to read identity tag for this cancer type.

“Although it has been suggested that hundreds of any cancer type would have to be sequenced at great depth to make clinically useful discoveries,” says Huntsman, “we had hypothesized that knowledge could be gained from much smaller studies if the cancers were carefully selected and represented clinically homogenous diseases. There are many rarer cancer types, like granulosa cell tumours that fit that bill and based upon our success in decoding granulosa cell tumours we are focusing on other rare tumours in what could be described as a guerrilla war on cancer. We hope that these studies will not only help future patients with rare tumours but will also teach us about more common ones as well.”

“This cancer is unique,” says Dr. Dianne Miller, gynecologic oncologist at BC Cancer Agency and Vancouver General Hospital. “For patients with this tumour type, it means they should all have the same response to the same treatment. And now that we have this pathway, we can look for existing cancer drugs that might work on this particular gene mutation to make the cancer disappear.”

The OvCaRe team was able to make this discovery because of the multidisciplinary nature of the group, which crosses two provincial health authorities and is made up of gynaecologists, pathologists, bioinformatics specialists, and oncologists. Further enhancing the team’s success is the centralization of patient treatment and record keeping.

“We are excited by this paper,” says Dr. Michael Birrer, professor, Department of Medicine, Harvard Medical School and director GYN/Medical Oncology, Medicine, Massachusetts General Hospital. “The ovarian cancer research and care community now has new biologic insights into this poorly understood tumour and a potential therapeutic target. More importantly, this tour de force study reveals the power of genomic approaches to cancer, particularly rare tumours.”

Ovarian cancer affects about one in 70 Canadian women. Approximately 2500 new cases are diagnosed each year and the five-year survival rate is only 30 per cent.

This study was supported by donors to VGH & UBC Hospital Foundation and the BC Cancer Foundation, and Genome BC for the development of Illumina sequencing at the BC Cancer Agency’s Genome Sciences Centre. OvCaRe and the BC Cancer Agency’s Genome Sciences Centre are also supported by the Michael Smith Foundation for Health Research.

Ovarian Cancer Research Program (OvCaRe) is a multidisciplinary research program involving clinicians and research scientists in gynaecology, pathology, and medical oncology. OvCaRe is a unique collaboration between the BC Cancer Agency, Vancouver Coastal Health Research Institute, and the University of British Columbia. Funding is provided through donations to VGH & UBC Hospital Foundation and the BC Cancer Foundation, who, in a joint partnership created a campaign to raise funds to make OvCaRe possible. The OvCaRe team is considered a leader in ovarian cancer research, breaking new ground in better identifying, understanding, and treating this disease. Earlier this year, the team discovered that ovarian cancer was not just one disease, but rather made up of several distinct subtypes.

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Related N Engl J Med Editorial:  Shendure J, Stewart, CJ. Cancer Genomes on a Shoestring Budget. N Engl J Med 2009 0: NEJMe0903433 (Full Text).

Additional Reference:  Köbel M, Kalloger SE, Boyd N,et. al. Ovarian carcinoma subtypes are different diseases: implications for biomarker studies. PLoS Med. 2008 Dec 2;5(12):e232. PubMed PMID: 19053170; PubMed Central PMCID: PMC2592352.

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