Green Tea: Mixed Reviews For Cancer Prevention

Lifestyle choices are pieces of the cancer prevention puzzle, but exactly which steps to take remain unclear, even to scientists. Still, more and more individuals are incorporating small changes into their daily routine — such as drinking green tea — in hopes of keeping cancer risk at bay.Is it working? A large new Cochrane review of studies that examined the affect of green tea on cancer prevention has yielded conflicting results.

Researchers looked at 51 medium- to high-quality studies that included more than 1.6 million participants. The studies focused on the relationship between green tea consumption and a variety of cancers, including breast, lung, digestive tract, urological prostate, gynecological and oral cancers.

The comprehensive review analyzed studies conducted from 1985 through 2008. Many of the reviewed studies took place in Asia, where tea drinking is widespread and part of the daily routine for many.

The review appears in a recent issue of The Cochrane Library, which is a publication of The Cochrane Collaboration, an international organization that evaluates medical research. Systematic reviews draw evidence-based conclusions about medical practice after considering both the content and quality of existing medical trials on a topic.

“Despite the large number of included studies the jury still seems to be out on the question of whether green tea can in fact prevent the development of various cancer types,” said lead review author Katja Boehm, Ph.D. Since people drink varying amounts of green tea, and different types of cancers vary in how they grow, it is impossible to state definitively that green tea is “good” for cancer prevention.

“One thing is certain…green tea consumption can never account for cancer prevention alone,” said Boehm, a member of the Unconventional and Complementary Methods in Oncology Study Group in Nuremburg, Germany.

Three types of tea — black, green and oolong — come from the plant Camellia sinensis, and all contain polyphenols. Catechins, a subgroup of the polyphenols, are powerful antioxidants. Some say the polyphenols in green tea are unique, preventing cell growth and thus having the potential to prevent cancer.

The review found that green tea had limited benefits for liver cancer, but found conflicting evidence for other gastrointestinal cancers, such as cancer of the esophagus, colon or pancreas. One study found a decreased risk of prostate cancer for men who consumed higher quantities of green tea or its extracts.

The review did not find any benefit for preventing death from gastric cancer, and found that green tea might even increase the risk of urinary bladder cancer. Despite conflicting findings, there was “limited moderate to strong evidence” of a benefit for lung, pancreatic and colorectal cancer. None of the studies that simply observed a group of people over time found a benefit for breast cancer prevention. However, both of the case control studies — which compare people without a condition to people with it — found a positive association between green tea consumption and a decreased risk of breast cancer.

Nagi Kumar, Ph.D., director of Nutrition Research at Moffitt Cancer Center in Tampa, Fla., is optimistic about the potential for green tea in cancer prevention. “The substances found in green tea are certainly promising,” Kumar said. “The field now has progressed to where we [can]…test the effectiveness and safety of green tea polyphenols using a drug form similar to the constituents in tea to see if we can prevent cancer progression. Time will tell.”

Kumar said the Cochrane review was “more an inventory of studies completed rather than a systematic scientific review,” adding that “the discussion lacks a scientific approach in the interpretation of the discordant findings.”

Kumar also noted that several groups are conducting randomized clinical trials, including one comprising six institutions: the Moffitt Cancer Center and the James A Haley VA Medical Center, University of Chicago, Jefferson in Philadelphia, University of Florida and Louisiana State University.

Both scientists agreed that more research is a good idea. Boehm said she highly recommends the conduction of a large, well-designed, study with adequate green tea consumption levels.

“The review provides where we have been in this field of research and where we are going and how much more we have on hand,” Kumar said. “Although not as thorough as I would like it, it is a good quality review.”

Therefore, while the questions about green tea consumption and cancer prevention remain unanswered, one thing remains clear: It is fine to consume green tea if you enjoy it and it might prove beneficial in the over time.

“If not exceeding the daily recommended allowance those who enjoy a cup of green tea should continue its consumption,” Boehm said. “Drinking green tea appears to be safe at regular, habitual and moderate use at its recommended dosage of up to 1200 ml/day.” That comes to a little over five cups a day.

Handle With Care: Telomeres Resemble DNA Fragile Sites

Telomeres, the repetitive sequences of DNA at the ends of linear chromosomes, have an important function: They protect vulnerable chromosome ends from molecular attack. Researchers at Rockefeller University now show that telomeres have their own weakness. They resemble unstable parts of the genome called fragile sites where DNA replication can stall and go awry. But what keeps our fragile telomeres from falling apart is a protein that ensures the smooth progression of DNA replication to the end of a chromosome.The research, led by Titia de Lange, head of the Laboratory of Cell Biology and Genetics, and first author Agnel Sfeir, a postdoctoral associate in the lab, suggests a striking similarity between telomeres and common fragile sites, parts of the genome where breaks tend to occur, albeit infrequently. (Humans have 80 common fragile sites, many of which have been linked to cancer.) De Lange and Sfeir found that these newly discovered fragile sites make it difficult for DNA replication to proceed, a discovery that unveils a new replication problem posed by telomeres.

At the center of the discovery is a protein known as TRF1, which de Lange, in an effort to understand how telomeres protect chromosome ends, discovered in 1995. Using a conditional mouse knockout, de Lange and Sfeir have now revealed that TRF1, which is part of a six-protein complex called shelterin, enables DNA replication to drive smoothly through telomeres with the aid of two other proteins.

“Telomeric DNA has a repetitive sequence that can form unusual DNA structures when the DNA is unwound during DNA replication,” says de Lange. “Our data suggest that TRF1 brings in two proteins that can take out these structures in the telomeric DNA. In other words, TRF1 and its helpers remove the bumps in the road so that the replication fork can drive through.”

The work, published in the July 10 issue of Cell, began when Sfeir deleted TRF1 and saw that the telomeres resembled common fragile sites, suggesting that TRF1 protects telomeres from becoming fragile. Instead of a continuous string of DNA, the telomeres were broken into fragments of twos and threes. To see if the replication fork stalls at telomeres, de Lange and Sfeir joined forces with Carl L. Schildkraut, a researcher at Albert Einstein College of Medicine in New York City. Using a technique called SMARD, the researchers observed the dynamics of replication across individual DNA molecules — the first time this technique has been used to study telomeres. In the absence of TRF1, the fork often stalled for a considerable amount of time.

The only other known replication problem posed by telomeres was solved in 1985 when it was shown that the enzyme telomerase elongates telomeres, which shorten during every cell division. The second problem posed by telomeres, the so-called end-protection problem, was solved by de Lange and her colleagues when they found that shelterin protects the ends of linear chromosomes, which look like damaged DNA, from unnecessary repair. Working with TRF1, the very first shelterin protein ever to be identified, de Lange and Sfeir have not only unveiled a completely unanticipated replication problem at telomeres, they have also shown how it is solved.

The research lays new groundwork for the study of common fragile sites throughout the genome, explains de Lange. “Fragile sites have always been hard to study because no specific DNA sequence preceeds or follows them,” she says. “In constrast, telomeres represent fragile sites with a known sequence, which may help us understand how common fragile sites break throughout the genome — and why.”

HIV-related Death: Predicting Fatal Fungal Infections

In a study published in The Journal of Infectious Diseases, researchers from Albert Einstein College of Medicine of Yeshiva University have identified cells in blood that predict which HIV-positive individuals are most likely to develop deadly fungal meningitis, a major cause of HIV-related death. This form of meningitis affects more than 900,000 HIV-infected people globally—most of them in sub-Saharan Africa and other areas of the world where antiretroviral therapy for HIV is not available.A major cause of fungal meningitis is Cryptococcus neoformans, a yeast-like fungus commonly found in soil and in bird droppings. Virtually everyone has been infected with Cryptococcus neoformans, but a healthy immune system keeps the infection from ever causing disease.

The risk of developing fungal meningitis from Cryptococcus neoformans rises dramatically when people have weakened immunity, due to HIV infection or other reasons including the use of immunosuppressive drugs after organ transplantation, or for treating autoimmune diseases or cancer. Knowing which patients are most likely to develop fungal meningitis would allow costly drugs for preventing fungal disease to be targeted to those most in need. (In the U.S., the widespread use of antiretroviral therapy by HIV-infected people, and their preventive use of anti-fungal drugs, has dramatically reduced their rate of fungal meningitis from Cryptococcus neoformans to about 2%.)

In this study, Liise-anne Pirofski, M.D., describes a technique for predicting which HIV-infected patients are at greatest risk for developing fungal meningitis caused by Cryptococcus neoformans. Dr. Pirofski is chief in the division of infectious diseases at Einstein.

Dr. Pirofski and her colleagues counted the number of immune cells known as IgM memory B cells in the bloodstream of three groups of individuals: people infected with HIV who had a history of fungal meningitis caused by Cryptococcus neoformans; people infected with HIV but with no history of the disease; and those with no history of either HIV infection or the disease.

"We were astounded to find a profound difference in the level of these IgM memory B cells between the HIV-infected groups," said Dr. Pirofski. "The HIV-infected people with fungal meningitis caused by Cryptococcus neoformans had much lower levels of these cells."

The research team wanted to know if the lower levels of IgM memory B cells in certain HIV-infected individuals resulted from the fungal disease, or whether their reduced levels of these cells preceded their development of the disease.

To find out, Dr. Pirofski analyzed frozen blood samples taken from HIV-infected patients before they had developed fungal meningitis due to Cryptococcus neoformans. Years before these HIV-infected patients were diagnosed with meningitis, their blood had far fewer IgM memory B cells than HIV-infected patients who didn't come down with the disease. This suggests that some people are predisposed to develop fungal meningitis because they have low levels of IgM memory B cells that may be due to their genetic makeup.

These findings could be important for many other immunocompromised patients in addition to those infected with HIV. "We think that knowing whether transplant recipients or other patients taking immunosuppressive drugs have low numbers of IgM memory B cells could be useful in deciding which patients should receive antifungal drugs to prevent meningitis caused by Cryptococcus neoformans," says Dr. Pirofski.

Krishanthi Subramanian, Ph.D., who did her thesis work in Dr. Pirofski's laboratory, is the first author of the study.