Tag Archives: melanoma

  Two more studies found that higher levels of vitamin D in the blood are associated with better health outcomes - one study found a lower risk of breast cancer, especially among postmenopausal women, and in the other - better outcomes after a metastatic melanoma diagnosis.

The breast cancer study suggested that a fairly high blood level of vitamin D (25(OH)D serum level>38.0 ng/mL) was associated with a lower risk of breast cancer. But overall they found that women supplementing with vitamin D (more than 4 times a week) at any dose had a lower risk of breast cancer over a 5 year period than those not supplementing with vitamin D. From Environmental Health Perspectives:

Serum Vitamin D and Risk of Breast Cancer within Five Years

Vitamin D is an environmental and dietary agent with known anticarcinogenic effects, but protection against breast cancer has not been established. We evaluated the association between baseline serum 25-hydroxyvitamin D [25(OH)D] levels, supplemental vitamin D use, and breast cancer incidence over the subsequent 5 y of follow-up. From 2003-2009, the Sister Study enrolled 50,884 U.S. women 35-74 y old who had a sister with breast cancer but had never had breast cancer themselves. Using liquid chromatography-mass spectrometry, we measured 25(OH)D in serum samples from 1,611 women who later developed breast cancer and from 1,843 randomly selected cohort participants.

We found that 25(OH)D levels were associated with a 21% lower breast cancer hazard (highest versus lowest quartile). Analysis of the first 5 y of follow-up for all 50,884 Sister Study participants showed that self-reported vitamin D supplementation was associated with an 11% lower hazard. These associations were particularly strong among postmenopausal women.

In this cohort of women with elevated risk, high serum 25(OH)D levels and regular vitamin D supplement use were associated with lower rates of incident, postmenopausal breast cancer over 5 y of follow-up. These results may help to establish clinical benchmarks for 25(OH)D levels; in addition, they support the hypothesis that vitamin D supplementation is useful in breast cancer prevention.

The first sentence in the melanoma study lays out what is widely known: "Vitamin D deficiency (≤20 ng/mL) is associated with an increased incidence and worse prognosis of various types of cancer including melanoma." Studies show that the relationship between vitamin D, sunlight exposure, and melanoma is complicated in a number of ways, including: sun exposure may be associated with increased survival in patients with melanoma. which may mean that vitamin D has a protective role in patients with melanoma. Several studies suggest that vitamin D may delay melanoma recurrence and improve overall prognosis. The study also found that metastatic melanoma patients with vitamin D deficiency who are unable to or don't raise their vitamin D blood levels (25(OH)D3) have a worse outcome compared to those who are are able to markedly increase (by greater than >20 ng/mL) their 25(OH)D3 levels. From Oncotarget:

Vitamin D deficiency is associated with a worse prognosis in metastatic melanoma

Vitamin D deficiency (≤20 ng/mL) is associated with an increased incidence and worse prognosis of various types of cancer including melanoma. A retrospective, single-center study of individuals diagnosed with melanoma from January 2007 through June 2013 who had a vitamin D (25(OH)D3) level measured within one year of diagnosis was performed to determine whether vitamin D deficiency and repletion are associated with melanoma outcome.

A total of 409 individuals diagnosed with histopathology-confirmed melanoma who had an ever measured serum 25(OH)D3 level were identified. 252 individuals with a 25(OH)D3 level recorded within one year after diagnosis were included in the study .... A worse melanoma prognosis was associated with vitamin D deficiency, higher stage, ulceration, and higher mitotic rate. In patients with stage IV metastatic melanoma, vitamin D deficiency was associated with significantly worse melanoma-specific mortality. Patients with metastatic melanoma who were initially vitamin D deficient and subsequently had a decrease or ≤20 ng/mL increase in their 25(OH)D3 concentration had significantly worse outcomes compared to non-deficient patients who had a >20 ng/mL increase. Our results suggest that initial vitamin D deficiency and insufficient repletion is associated with a worse prognosis in patients with metastatic melanoma.

 A number of recent studies looked at vitamin D and various diseases. All showed benefits of higher vitamin D levels in the blood: lower rates of cancer incidence, improved heart function in those with heart failure, lower rates of leukemia incidence, lower rates of breast cancer, and less aggressive breast and prostate cancer. However, one study found no benefits to vitamin D supplementation during pregnancy and the child's asthma risk. Older studies found low levels of vitamin D linked to higher risk of premenopausal breast cancer, and also to thicker melanomas at diagnosis (the thinner the melanoma, the better the prognosis).

Everyone agrees that sunshine is an excellent source of vitamin D, but there is still disagreement over what are the best daily vitamin D supplement dosages, or even what are optimal levels of vitamin D in the blood (measured as serum 25-hydroxyvitamin D or 25(OH)D). In 2010, the Institute of Medicine (IOM) concluded that levels lower than 12 ng/ml represented a vitamin D deficiency and recommended a target of 20 ng/ml, which could be met in most healthy adults (ages 19 to 70) with 600 International Units of vitamin D each day. Since then most researchers have argued for higher blood serum levels: most agreeing that over 30 ng/ml is best, while some advocating 50 ng/ml or more. But even what's too high (and could cause problems) is debated. Many vitamin D supporters now advocate taking 800 to 1,000 IUs of vitamin D daily (some say up to 4000 IUs daily is OK). Remember to look for vitamin D3 supplements, not D2.

This study found that higher levels of vitamin D (measured as serum 25(OH)D) are better, with 25(OH)D concentrations of at least 40 ng/ml best to reduce cancer risk (all types of cancer). From Medical Xpress: Higher levels of vitamin D correspond to lower cancer risk, researchers say

Researchers at University of California, San Diego School of Medicine report that higher levels of vitamin D - specifically serum 25-hydroxyvitamin D - are associated with a correspondingly reduced risk of cancer. The findings are published in the April 6, online issue of PLOS ONE.

Garland and his late brother, Frank, made the first connection between vitamin D deficiency and some cancers in 1980 when they noted populations at higher latitudes (with less available sunlight) were more likely to be deficient in vitamin D, which is produced by the body through exposure to sunshine, and experience higher rates of colon cancer. Subsequent studies by the Garlands and others found vitamin D links to other cancers, such as breast, lung and bladder.

The new PLOS ONE study sought to determine what blood level of vitamin D was required to effectively reduce cancer risk....The only accurate measure of vitamin D levels in a person is a blood test....Cancer incidence declined with increased 25(OH)D. Women with 25(OH)D concentrations of 40 ng/ml or greater had a 67 percent lower risk of cancer than women with levels of 20 ng/ml or less.

Garland does not identify a singular, optimum daily intake of vitamin D or the manner of intake, which may be sunlight exposure, diet and/or supplementation. He said the current study simply clarifies that reduced cancer risk becomes measurable at 40 ng/ml, with additional benefit at higher levels. "These findings support an inverse association between 25(OH)D and risk of cancer," he said, "and highlight the importance for cancer prevention of achieving a vitamin D blood serum concentration above 20 ng/ml, the concentration recommended by the IOM for bone health."

From Science Daily: Vitamin D improves heart function, study finds

A daily dose of vitamin D3 improves heart function in people with chronic heart failure, a five-year research project has found. The study involved more than 160 patients who were already being treated for their heart failure using proven treatments including beta-blockers, ACE-inhibitors and pacemakers.

Participants were asked to take vitamin D3 or a dummy (placebo) tablet for one year. Those patients who took vitamin D3 experienced an improvement in heart function which was not seen in those who took a placebo....In the 80 patients who took Vitamin D3, the heart's pumping function improved from 26% to 34%. In the others, who took placebo, there was no change in cardiac function.

Disappointing results. From Medscape: Vitamin D Disappoints: Prenatal Supplementation and Childhood Asthma

Two recent clinical trials examined maternal supplementation with vitamin D and postpregnancy offspring outcomes for asthma and wheezing....However, with respect to preventing asthma in offspring, there is no clear evidence for vitamin D supplementation in pregnant women.

From PLOS ONE: Vitamin D Deficiency at Melanoma Diagnosis Is Associated with Higher Breslow Thickness

Vitamin D deficiency at the time of melanoma diagnosis is associated with thicker tumours that are likely to have a poorer prognosis. Ensuring vitamin D levels of 50 nmol/L or higher in this population could potentially result in 18% of melanomas having Breslow thickness of <0.75 mm rather than ≥0.75 mm.

Reported in 2013. From Medical Express: Low vitamin D levels linked to high risk of premenopausal breast cancer

A prospective study led by researchers from the University of California, San Diego School of Medicine has found that low serum vitamin D levels in the months preceding diagnosis may predict a high risk of premenopausal breast cancer. The study of blood levels of 1,200 healthy women found that women whose serum vitamin D level was low during the three-month period just before diagnosis had approximately three times the risk of breast cancer as women in the highest vitamin D group. 

A 2011 meta-analysis by Garland and colleagues estimated that a serum level of 50 ng/ml is associated with 50 percent lower risk of breast cancer. While there are some variations in absorption, those who consume 4000 IU per day of vitamin D from food or a supplement normally would reach a serum level of 50 ng/ml.

This study, even though done on mice, reinforces previous research that taking antioxidant supplements are linked to higher rates of cancer or the spread of cancer (metastases). Here it is linked to the spread of metastatic skin cancer. The researchers say that the overall conclusion from the various studies is that antioxidants protect healthy cells from free radicals that can turn them into malignancies, but may also protect a tumor once it has developed. They also suggest that suntan lotions and skin lotions containing vitamin E and beta-carotene may have the same negative effect and are now studying that possibility. However, note that many, many studies find that eating foods does NOT find negative effects, but only beneficial ones for health. The October 5, 2015 post also discussed why supplements containing large doses of antioxidants (such as beta-carotene) don't work, and can even cause harm. Bottom line: Eat fruits and vegetables daily for numerous health benefits, but skip the antioxidant supplements. From Science Daily:

Antioxidants cause malignant melanoma to metastasize faster

Antioxidants can double the rate of melanoma metastasis in mice, new research shows. The results reinforce previous findings that antioxidants hasten the progression of lung cancer. People with cancer or an elevated risk of developing the disease should avoid nutritional supplements that contain antioxidants, the researchers say.

Researchers at Sahlgrenska Academy, University of Gothenburg, demonstrated in January 2014 that antioxidants hastened and aggravated the progression of lung cancer. Mice that were given antioxidants developed additional and more aggressive tumors. Experiments on human lung cancer cells confirmed the results. Given well-established evidence that free radicals can cause cancer, the research community had simply assumed that antioxidants, which destroy them, provide protection against the disease. Found in many nutritional supplements, antioxidants are widely marketed as a means of preventing cancer. Because the lung cancer studies called the collective wisdom into question, they attracted a great deal of attention.

The follow-up studies at Sahlgrenska Academy have now found that antioxidants double the rate of metastasis in malignant melanoma, the most perilous type of skin cancer. Science Translational Medicine published the findings on October 7. "As opposed to the lung cancer studies, the primary melanoma tumor was not affected," Professor Bergö says. "But the antioxidant boosted the ability of the tumor cells to metastasize, an even more serious problem because metastasis is the cause of death in the case of melanoma. The primary tumor is not dangerous per se and is usually removed."

Experiments on cell cultures from patients with malignant melanoma confirmed the new results. "We have demonstrated that antioxidants promote the progression of cancer in at least two different ways," Professor Bergö says. The overall conclusion from the various studies is that antioxidants protect healthy cells from free radicals that can turn them into malignancies but may also protect a tumor once it has developed.

Avoid supplements: Taking nutritional supplements containing antioxidants may unintentionally hasten the progression of a small tumor or premalignant lesion, neither of which is possible to detect. "Previous research at Sahlgrenska Academy has indicated that cancer patients are particularly prone to take supplements containing antioxidants," Dr. Bergö says. Our current research combined with information from large clinical trials with antioxidants suggests that people who have been recently diagnosed with cancer should avoid such supplements."

The role of antioxidants is particularly relevant in the case of melanoma, not only because melanoma cells are known to be sensitive to free radicals but because the cells can be exposed to antioxidants by non-dietary means as well. "Skin and suntan lotions sometimes contain beta carotene or vitamin E, both of which could potentially affect malignant melanoma cells in the same way as antioxidants in nutritional supplements," Professor Bergö says. How antioxidants in lotions affect the course of malignant melanoma is currently being explored. "We are testing whether antioxidants applied directly to malignant melanoma cells in mice hasten the progression of cancer in the same way as their dietary counterparts," Professor Bergö says. 

Citrus paradisi (Grapefruit, pink) white bg.jpgWill these research results hold up over time? It is known that certain fruits (citrus fruits and juices) and vegetables contain photosensitizing chemicals called psoralens, and the researchers suspected that a high intake of citrus products over time could make individuals more susceptible to melanoma than people who rarely ate citrus fruits. During more than 2 decades of following more than 100,000 persons they found 1840 melanomas , And yes, even though there were relatively few melanomas, they did find a dose-dependent relationship between citrus product consumption and melanoma risk, specifically that ingesting citrus fruit 1.6 or more times per day had a 36% higher risk for melanoma than people who ate it less than twice per week. But this association was only with whole grapefruit and orange juice, and weirdly, not with consumption of grapefruit juice or whole oranges. Before people panic, remember that citrus fruits have all sorts of great health benefits and should be eaten. From Science Daily:

Can orange juice, grapefruit raise your melanoma risk?

People who enjoy a glass of orange juice or some fresh grapefruit in the morning may face a slightly increased risk of melanoma—the least common but most deadly form of skin cancer. That's the finding from a study of more than 100,000 U.S. adults followed for about 25 years. Researchers discovered that those who regularly consumed orange juice or whole grapefruit had a higher risk of developing melanoma, compared to people who avoided those foods.

Experts were quick to stress that the findings, reported online June 29 in the Journal of Clinical Oncology, do not prove that citrus foods help cause skin cancer. It is plausible, however, that certain compounds in citrus explain the association, said senior researcher Dr. Abrar Qureshi, chair of dermatology at Brown University and a dermatologist at Rhode Island Hospital, in Providence.

Citrus foods contain particular "photoactive" chemicals—namely, psoralens and furocoumarins—that are known to make the skin more sensitive to the sun when they're applied topically, Qureshi said."You'll see children get a sunburn in spots where a citrus popsicle dripped down the chin, for example," Qureshi explained.

But even if citrus foods potentially make some people susceptible to sunburn, it's not orange juice that should be avoided, Qureshi said. "The citrus can't hurt you without the excessive sun exposure," he pointed out. So the message remains the same, Qureshi said: Protect your skin from soaking up too many rays by staying in the shade, using sunblock and wearing a hat. "I don't think the general public should make any changes based on this study," said Berwick, a professor of dermatology at the University of New Mexico in Albuquerque. 

For the study, the researchers analyzed data from two long-running studies of U.S. health professionals. Every couple of years, the participants answered detailed surveys on their health and lifestyle. Over about 25 years, more than 1,800 people developed melanoma and the risk was higher among those who regularly drank orange juice or ate whole grapefruit. That was true, the researchers found, even when several other factors were taken into account—including people's reports of their overall sun exposure and history of bad sunburns.

People who had orange juice at least once a day were about 25 percent more likely to develop melanoma than those who drank the juice less than weekly. Similarly, people who ate whole grapefruit at least three times a week had a 41 percent higher melanoma risk, versus those who never ate it. On the other hand, there was no connection between melanoma risk and either whole oranges or grapefruit juice, the researchers found.

Qureshi did offer a potential explanation for why only orange juice and whole grapefruit may be tied to melanoma risk."There are different types of these photoactive compounds in different parts of the fruit," he said. So, it's possible that not all citrus fruits are alike when it comes to melanoma risk. Plus, Qureshi said, heat—like that used in pasteurizing juice—neutralizes the photoactive compounds. That might help explain why grapefruit juice was not connected to melanoma risk.

This recent scientific (and yes, technical) article discusses the tantalizing promise of treating cancer, especially melanoma, with infections and certain vaccines. Much discussion of how two vaccines that are already out there may prevent some cancers such as melanoma and leukemia (vaccination with Bacille Calmette-Guerin (BCG) of newborns and vaccination with the yellow fever 17D vaccine of adults).This recent article is a further development on what was discussed in the last post (Injecting a person with a bacterial extract - called Coley's toxins or Coley toxins - to cause an infection, and so treat cancer). From BioMed Central:

The biography of the immune system and the control of cancer: from St Peregrine to contemporary vaccination strategies

In 1875 Campbell de Morgan, a surgeon at the Middlesex Hospital in London, reported that regressions and remissions of cancers sometimes occurred after post-operative infections, particularly the streptococcal infection erysipelas...

Campbell de Morgan’s observation that remissions sometimes occurred after post-operative streptococcal infections inspired some workers to undertake the risky procedure of deliberately inducing erysipelas in cancer patients. Subsequently, an American surgeon, William Coley, developed bacteria-free extracts of streptococci and other bacteria (“Coley toxins”) and reported their successful use in the therapy of cancers, especially sarcomas, between 1881 and 1936 . Unfortunately Coley, a mild mannered and unassuming gentleman, did not adhere to rigorous scientific protocols in his studies and he was marginalized by forceful personalities advocating radiotherapy. Notwithstanding, an analysis of his results with cancer deemed inoperable undertaken in 1994 revealed a remission rate of 64% and a five-year survival rate of 44%, results equal to or better than those with modern therapies [14]. 

It is also now appreciated that chronic inflammation is an essential element of cancers and it has indeed been termed ‘the other half of the tumour’ [37]. The normal healing process relies on inflammation, collagen production, angiogenesis and cell proliferation and, in a description of the similarities between tumour stroma formation and wound healing, tumours have been referred to as “wounds that do not heal” [38], 

The relationship between infection, and associated inflammation, and cancer is a complex and paradoxical one and there are several well described examples of cancer being the direct consequence of infection [41]. Around 2 million of the 12.7 million new cancer cases worldwide in 2008 (16.1%) were assumed to be related to infection, principally Helicobacter pylori, hepatitis viruses, and the human papilloma virus, with a higher proportion in developing countries (22.9%) than in developed ones (7.4%) [42]. The large majority of cases of cancer, especially those in the developed nations, are therefore not caused by infection – on the contrary, there is growing evidence that a history of certain infections and environmental exposure to certain populations of micro-organisms, as well as some types of vaccination, may induce patterns of immune reactivity that reduce the risk of at least some cancers

A study of an adult population in Italy demonstrated an association between a history of common childhood infectious diseases (measles, chickenpox, rubella, mumps and pertussis) and the risk of developing chronic lymphatic leukaemia (CLL), with a strong inverse relationship between the risk of CLL and the number of infections (p = 0.002) [47]. 

In the 1990s Kölmel and colleagues established a working group – Febrile Infections and Melanoma (FEBIM) – within the European Organization for Research and Treatment of Cancer (EORTC). Based on a pilot study [79] this group undertook a series of studies to establish the relationship between the risk for developing melanoma and a history of, initially, infectious diseases [80], and, subsequently, also of vaccinations [81,82].

In the first report of the FEBIM group a significant level of protection against melanoma in those with a history of certain severe infections (sepsis, Staph. aureus infection, pneumonia, pulmonary tuberculosis) with fever of over 38.5°C was demonstrated [80]. It should, however, be noted that these apparently melanoma-protective infectious diseases have become rare in the industrialized nations. 

It is claimed that, as a result of recent observational studies, measures for prevention of some malignancies such as melanoma and certain forms of leukaemia are already at hand: vaccination with Bacille Calmette-Guérin (BCG) of new-borns and vaccination with the yellow fever 17D (YFV) vaccine of adults. While the evidence of their benefit for prevention of malignancies requires substantiation, the observations that vaccinations with BCG and/or vaccinia early in life improved the outcome of patients after surgical therapy of melanoma are of practical relevance as the survival advantage conferred by prior vaccination is greater than any contemporary adjuvant therapy.