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Published on Leave a comment on Vitamin D Level Linked to Cancer Risk

 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.

Published on Leave a comment on Many Health Benefits of Nuts and Seeds

Nice summary article about the known benefits of nuts and seeds, and the nutrients they contain. Bottom line: all nuts and seeds are beneficial to health. It's best to eat a variety of nuts, and eat some nuts daily or at least a few times a week. A typical serving is 1/4 cup or small handful of nuts. Go to the article for the complete nut and seed list and a nut and seed nutrient chart. From Today's Dietician:

The Wonders of Nuts and Seeds

Nuts and seeds have been part of the human diet since Paleolithic times. A few nuts, such as almonds and walnuts, and seeds, namely flax and chia, get most of the glory, but the fact is each nut and seed brings something beneficial to the table. While exact nutrient compositions vary, nuts and seeds are rich sources of heart-healthy fats, fiber, plant protein, essential vitamins and minerals, and other bioactive compounds, including an array of phytochemicals that appear to have antioxidant and anti-inflammatory properties.

A wealth of data from prospective observational studies and clinical trials suggest that tree nut consumption reduces the risk of several chronic diseases, including cardiovascular disease (CVD), type 2 diabetes, and some forms of cancer. Moreover, there may be benefits for cognitive health. Adding support to these findings is research suggesting that incorporating tree nuts in the diet lowers the risk of conditions that contribute to disease, such as hypertension, high cholesterol, insulin resistance, abdominal obesity, endothelial dysfunction, oxidative stress, and inflammation. Various components of nuts, such as heart-healthy monounsaturated and polyunsaturated fats, plant-based protein, fiber, vitamins, minerals, and phytochemicals may work together to offer protection against oxidation, inflammation, cancer, and CVD.

Recent findings from the PREDIMED trial suggest that a Mediterranean diet that includes one serving of nuts per day protects against heart attack, stroke, or death from other cardiovascular causes in people at high risk due to type 2 diabetes or metabolic syndrome. PREDIMED data also suggest that eating more than three servings of nuts per week reduces risk of death from all causes, especially if also following a Mediterranean diet. Subjects who frequently consumed both total nuts and walnuts had a lower rate of death from cancer....While the number of nuts per serving varies by type, a typical serving is 1 oz or about 1/4 cup or a small handful (palm of the hand only)....

• Almonds are high in monounsaturated fats, which may explain their association with lower LDL cholesterol levels and reduced heart disease risk. The antioxidant function of the vitamin E (37% DV in 1 oz) in almonds along with their magnesium and potassium also may play a role in cardiovascular health. One study found that almonds may reduce LDL as much as statins.

• Brazil and cashew nuts: Technically a seed, 1 oz of Brazil nuts contains a whopping 767% DV for selenium. That's over the Tolerable Upper Intake Level of 400 mcg. But eating two Brazil nuts per day has been shown to be an effective way to increase blood levels of this antioxidant mineral healthfully. Cashews are lower in fat than most nuts and contain anacardic acid, which may improve insulin sensitivity and help prevent chronic inflammation.

• Pecans contain multiple forms of vitamin E and are especially rich in gamma-tocopherol, which has been shown to inhibit oxidation of LDL cholesterol. Oxidized LDL contributes to inflammation in the arteries and is a risk factor for CVD. Pecans also have the highest polyphenol and flavonoid content of the tree nuts.

• Pistachios: Two studies have shown that eating in-shell pistachios enhances feelings of fullness and satisfaction while reducing caloric intake. When eating in-shell pistachios, study subjects consumed about 40% fewer calories compared with pistachio kernels. Pistachios have the second highest polyphenol and flavonoid content of the tree nuts. 

• Walnuts are another excellent source of plant-based omega-3 fatty acids. Walnuts also boast the highest antioxidant content of the tree nuts, followed by pecans and cashew nuts. This makes walnuts one of the best nuts for anti-inflammatory benefits. Like pecans, walnuts are unusually rich in the gamma-tocopherol form of vitamin E. ... Walnut consumption among NHANES subjects is positively associated with cognitive function in both younger and older adults. They're a natural source of melatonin, which is critical in the regulation of sleep, circadian (daily) rhythms, and may play a role in walnuts' anticancer benefits.

Published on Leave a comment on More Sunlight Exposure, Live Longer?

A recent study in the Journal of Internal Medicine had interesting results regarding sun exposure - more was beneficial for health.

In the study, women were followed for 20 years, and any  deaths were put into one of 3 groups: as being from: heart disease, cancer, or other (non-heart disease and non-cancer). Swedish women followed for 20 years found that the more sunlight exposure they had, the longer the life expectancy, the less death from heart disease (cardiovascular disease) and causes other than heart disease or cancer (non-heart disease and non-cancer group), but the more skin cancer (basal cell carcinoma, squamous cell carcinoma and melanoma) they developed. 

Thus the main finding is of a dose-dependent relationship between sun exposure and life expectancy.

One surprising result was that nonsmokers who avoided sun exposure had a life expectancy similar to smokers in the highest sun exposure group. Those who avoided sun exposure had an increased risk of death mainly due to heart disease and "other causes" (non-cancer/non-heart disease).

I wondered about other cancers in this study, and this is all they had to say in the journal article:  "Thus, women with NMSC (nonmalignant skin cancer) had a 37% higher prevalence of other internal cancers than those without NMSC and a fourfold increased prevalence of MM (malignant melanoma). The incidence of other internal cancer was not increased subsequently on NMSC diagnosis."  I now have another question:  How do the women with cancer in the high and low sun exposure group do after another 10 or 20 years?  I would have liked for this study to continue longer.

The researchers felt that sunshine and vitamin D had a role in these results, and suggested that we need to rethink the "avoid sunshine" advice now given to people. In other words, some sunshine is good for health. From Science Daily:

Why do sunbathers live longer than those who avoid the sun?

New research looks into the paradox that women who sunbathe are likely to live longer than those who avoid the sun, even though sunbathers are at an increased risk of developing skin cancer. An analysis of information on 29,518 Swedish women who were followed for 20 years revealed that longer life expectancy among women with active sun exposure habits was related to a decrease in heart disease and noncancer/non-heart disease deaths, causing the relative contribution of death due to cancer to increase.

Whether the positive effect of sun exposure demonstrated in this observational study is mediated by vitamin D, another mechanism related to UV radiation, or by unmeasured bias cannot be determined. Therefore, additional research is warranted. 

"We found smokers in the highest sun exposure group were at a similar risk as non-smokers avoiding sun exposure, indicating avoidance of sun exposure to be a risk factor of the same magnitude as smoking," said Dr. Pelle Lindqvist, lead author of the Journal of Internal Medicine study. "Guidelines being too restrictive regarding sun exposure may do more harm than good for health."

Published on Leave a comment on Research Using Bacteria to Treat Cancer

The possibility of giving microbes in the future (whether bacteria, viruses, or fungi) to treat cancer is amazing. Of course big pharma is pursuing this line of research, which is called immunotherapy (stimulating the body's ability to fight tumors). The Bloomberg Business article discusses a number of big pharma companies entering the field and their main focus. The study in the journal Science finding that giving common beneficial bacteria (Bifidobacterium breve and Bifidobacterium longum) to mice to slow down melanoma tumor growth is a first step. The researchers themselves said that the 2 common beneficial bacteria species exhibited anti-tumor activity in the mice and was as effective as an immunotherapy in controlling the growth of skin cancer. But note that the bacteria needed to be live. Stay tuned....

From Bloomberg News: How Gut Bacteria Are Shaking Up Cancer Research

Top scientists at Roche Holding AG and AstraZeneca Plc are sizing up potential allies in the fight against cancer: the trillions of bacteria that live in the human body. "Five years ago, if you had asked me about bacteria in your gut playing an important role in your systemic immune response, I probably would have laughed it off," Daniel Chen, head of cancer immunotherapy research at Roche’s Genentech division, said in a phone interview. "Most of us immunologists now believe that there really is an important interaction there."

Two recent studies published in the journal Science have intrigued Chen and others who are developing medicines called immunotherapies that stimulate the body’s ability to fight tumors.In November, University of Chicago researchers wrote that giving mice Bifidobacterium, which normally resides in the gastrointestinal tract, was as effective as an immunotherapy in controlling the growth of skin cancer. Combining the two practically eliminated tumor growth. In the second study, scientists in France found that some bacterial species activated a response to immunotherapy, which didn’t occur without the microbes.  ...continue reading "Research Using Bacteria to Treat Cancer"

Published on Leave a comment on Low Vitamin D Levels Linked to Aggressive Cancer

Two recent studies link low vitamin D levels with more aggressive cancers: aggressive prostate cancer in men and more aggressive breast cancers (in mice and women). Researchers generally advise people to take 1000 to 2000 international units per day of vitamin D3 to maintain normal blood levels of of more than 30 nanograms/milliliter. The best source of vitamin D is sunlight, which is why vitamin D is frequently called the sunshine vitamin.

From Science Daily:  Low vitamin D predicts aggressive prostate cancer

A new study provides a major link between low levels of vitamin D and aggressive prostate cancer. Northwestern Medicine research showed deficient vitamin D blood levels in men can predict aggressive prostate cancer identified at the time of surgery.

"Vitamin D deficiency may predict aggressive prostate cancer as a biomarker," said lead investigator Dr. Adam Murphy, an assistant professor of urology at Northwestern University Feinberg School of Medicine and a Northwestern Medicine urologist. "Men with dark skin, low vitamin D intake or low sun exposure should be tested for vitamin D deficiency when they are diagnosed with an elevated PSA or prostate cancer. Then a deficiency should be corrected with supplements."

Aggressive prostate cancer is defined by whether the cancer has migrated outside of the prostate and by a high Gleason score. A low Gleason score means the cancer tissue is similar to normal prostate tissue and less likely to spread; a high one means the cancer tissue is very different from normal and more likely to spread. The study was part of a larger ongoing study of 1,760 men in the Chicago area examining vitamin D and prostate cancer. The current study included 190 men, average age of 64, who underwent a radical prostatectomy to remove their prostate from 2009 to 2014.

Of that group, 87 men had aggressive prostate cancer. Those with aggressive cancer had a median level of 22.7 nanograms per milliliter of vitamin D, significantly below the normal level of more than 30 nanograms/milliliter. The average D level in Chicago during the winter is about 25 nanograms/milliliter, Murphy noted....The Institute of Medicine recommends 600 international units of D per day, but Murphy recommends Chicago residents get 1,000 to 2,000 international units per day.

From Medical Xpress:  Vitamin D deficiency contributes to spread of breast cancer in mice, study finds

Breast tumors in laboratory mice deficient in vitamin D grow faster and are more likely to metastasize than tumors in mice with adequate levels of vitamin D, according to a preliminary study by researchers at the Stanford University School of Medicine.The research highlights a direct link between circulating vitamin D levels and the expression of a gene called ID1, known to be associated with tumor growth and breast cancer metastasis.

The finding builds upon several previous studies suggesting that low levels of vitamin D not only increase a person's risk of developing breast cancer, but are also correlated with more-aggressive tumors and worse prognoses. Although the research was conducted primarily in mice and on mouse cells, the researchers found in a study of 34 breast cancer patients that levels of circulating vitamin D were inversely correlated with the expression levels of ID1 protein in their tumors, and they confirmed that a vitamin D metabolite directly controls the expression of the ID1 gene in a human breast cancer cell line.

Once ingested or made by the body, vitamin D is converted through a series of steps into its active form, calcitriol. Calcitriol binds to a protein in cells called the vitamin D receptor, which then enters the cell's nucleus to control the expression of a variety of genes, including those involved in calcium absorption and bone health.

In the new study, Williams and Aggarwal investigated whether vitamin D levels affected the metastatic ability of mouse breast cancer cells implanted into the mammary fat pad of laboratory mice. One group of 10 mice was first fed a diet lacking in the vitamin for 10 weeks; the other 10 received a normal dose in their food. Mice fed a diet deficient in vitamin D developed palpable tumors an average of seven days sooner than their peers, and after six weeks of growth those tumors were significantly larger in size than those in animals with adequate vitamin D levels.

Published on Leave a comment on Treating Some Cancers With Probiotics in The Future?

Very exciting research IF it pans out - the idea of treating (some) cancers with probiotics (beneficial bacteria). This study was done on mice, and some mice started the probiotic mixture one week before they gave the mice the liver cancer, so...more limitations there. But the idea is so tantalizing and wonderful... And what was in the mixture of bacteria (called probiotic Prohep) that the mice ate that had beneficial results of shrinking liver tumors? The probiotic Prohep is composed of Lactobacillus rhamnosus GG (LGG), Escherichia coli Nissle 1917 (EcN), and heat inactivated VSL#3 (1:1:1).  VSL#3 contains: Streptococcus thermophilus, Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium infantis, Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus paracasei, and Lactobacillus delbrueckii. Note that Lactobacillus rhamnosus and some of the others are already found in many probiotic mixtures. From Medical Xpress:

Probiotics dramatically modulate liver cancer growth in mice

Medical research over the last decade has revealed the effects of the gut microbiome across a range of health markers including inflammation, immune response, metabolic function and weight....Previous studies have demonstrated the beneficial role of probiotics in reducing gastrointestinal inflammation and preventing colorectal cancer, but a new study published in the Proceedings of the National Academy of Sciences explored their immunomodulatory effects on extraintestinal tumors: specifically, in hepatocellular carcinoma (HCC). HCC is the most common type of liver cancer, and though it is relatively uncommon in the United States, it's the second-most deadly type of cancer worldwide and is particularly prevalent in regions with high rates of hepatitis. 

The researchers designed a study in a mouse model of HCC that quantified the immunological effects of a novel probiotic formulation called Prohep. They fed the mice Prohep for a week prior to tumor inoculation, and they observed a 40 percent reduction of tumor weight and size compared with control animals. Further, they established that the beneficial effects of the probiotics were closely related to the abundance of beneficial bacteria promoted by Prohep. These bacteria produce anti-inflammatory metabolites, which regulated pro-inflammatory immune cell populations via crosstalk between the gut and the liver tumor.

Among their findings, the researchers report that the probiotics reduced liver tumor growth by inhibiting angiogenesis, the process by which the body generates new blood vessels from existing ones, which is essential for tumor growth. They found significantly raised levels of hypoxic GLUT-1+, indicating that tumor reductions were due to hypoxia caused by reduced blood flow. Further, the tumors in the treated mice had 52 percent lower blood vessel area and 54 percent fewer vessel sprouts than the untreated mice.

They also determined that Prohep treatment down-regulated IL-17, a pro-inflammatory angiogenic factor. Because HCC is a highly vascularized tumor, the cancer is generally associated with high levels of IL-17 and an immune T-cell called T helper 17 (Th17), which is transported from the gut to HCC tumors via circulation. The researchers believe that reduced Th17 in tumor cells impedes the inflammation and angiogenesis and limits tumor growth. It's not surprising that they also found that probiotics increased the anti-inflammatory bacteria and metabolites present in the guts of treated mice. They conclude that Prohep intake has the capability of inhibiting tumor progression by modulating the gut microbiota.

Published on Leave a comment on Can Exercise Slow Cancer Growth?

Some studies with humans suggest that cancer growth is slowed with exercise, better cancer prognosis with regular exercise, and lowered cancer recurrence (e.g., exercise after prostate cancer diagnosis), but a recent study looked at the issue more in depth.

Yes, it was done in mice, but this way mice could be randomly assigned to different treatments (including various cancers - both fast and slow growing ones) and conditions in ways you can't with humans.

Why does exercise have these beneficial effects? Various suggestions include exercise causing changes in body composition, or sex hormone levels, or systemic inflammation, and changes in immune cell function. The researchers point out that cells of the immune system play dual roles in cancer: the immune system has a powerful capacity to combat cancer, but chronic inflammation has also been linked to formation of tumors (cancer). Thus, "mobilization" of cancer killing "immune cells during exercise might represent an indirect defense mechanism against cancer growth."

Bottom line: research suggests that exercise or vigorous activity is beneficial in those with cancer diagnosis.

From Science Daily: Running helps mice slow cancer growth

Here's one more benefit of exercise: mice who spent their free time on a running wheel were better able to shrink tumors (a 50% reduction in tumor size) compared to their less active counterparts. Researchers found that the surge of adrenaline that comes with a high-intensity workout helped to move cancer-killing immune (NK) cells toward lung, liver, or skin tumors implanted into the mice. The study appears Feb. 16, 2016 in Cell Metabolism.

"It is known that infiltration of natural killer (NK) immune cells can control and regulate the size of tumors, but nobody had looked at how exercise regulates the system," says senior study author Pernille Hojman, at the University of Copenhagen. "In our experiments, we tried to inject our mice with adrenaline to mimic this increase you see during exercise, and when we do that we see that the NK cells are mobilized to the bloodstream, and if there's a tumor present then the NK cells will find the tumor and home to it."

Hojman and her colleagues next used mice depleted of NK cells to show that the increase in number of NK cells at the site of the tumor was directly contributing to the reduction in size. Even with exercise and a full suite of other immune cells, without the NK cells these mice experienced the normal rate of cancer growth. Blocking the function of adrenaline also blunted the cancer-killing benefits of the running wheel.

The research group also discovered that an immune signaling molecule called IL-6 was the link between adrenaline-dependent mobilization of NK cells and tumor infiltration. It's known that IL-6 is released from muscle tissue during exercise, but Hojman presents evidence that adrenaline specifically hails IL-6 sensitive NK cells and that the IL-6 molecules helped guide the immune cells to the tumors.

"As someone working in the field of exercise and oncology, one of the main questions that cancer patients always ask is: how should I exercise? Can we do anything?" she says. "While it has previously been difficult to advise people about the intensity at which they should exercise, our data suggest that it might be beneficial to exercise at a somewhat high intensity in order to provoke a good epinephrine surge and hence recruitment of NK cells." (http://www.cell.com/cell-metabolism/pdf/S1550-4131(16)30003-1.pdf)

Published on Leave a comment on More On Rethinking Cancer Screening

The following is an excellent commentary by Dr. John Mandrola regarding an important British Medical Journal article that I posted about earlier (see Rethinking Cancer Screening). He has a highly regarded web-site and also frequently posts on Medscape. His view is that cancer screening "may be one of Medicine’s largest reversals. A reversal happens when something (testing or treatment) doctors did, and patients accepted, turned out to be non-beneficial." (www.drjohnm.org)

I can't overstate how big a reversal this is in medicine - it's huge, a paradigm change in the making. The reason for this is that studies show that overall death rates are basically the same in screened vs non-screened for mammography, colon, prostate, and lung cancer screening. This means our view of how cancer grows and spreads may have to be reexamined and changed. One possibility suggested by Dr. H. Gilbert Welch is that aggressive cancer is already "a systemic disease by the time it's detectable" (Oct. 28, 2015 post).  From Medscape:

In Cancer Screening, Why Not Tell the Truth?

The problem: cancer screening has not worked. Recent reviews of the evidence show that current-day screening techniques do not save lives. Worse, in many cases, these good-intentioned searches bring harm to previously healthy people.

I realize this sounds shocking. It did to me, too. Millions of women and men have had their breasts squished, veins poked, lungs irradiated, and bowels invaded in the name of "health" maintenance. I've been scolded for forgoing PSA tests and colonoscopy — "you should know better, John."....Anecdotes, however compelling, are not evidence. When you pull up a chair, open your computer, take a breath, suspend past beliefs, and look for the evidence that screening saves lives, it simply isn't there.

One reason that this many people (doctors and patients alike) have been misled about screening has been our collective attachment to the belief that if screening lowers disease-specific death rates, that would translate to lower overall mortality. That is: breast, lung, and colon cancer are bad diseases, so it makes sense that lowering death from those three types of cancer would extend life. It is not so.

In a comprehensive review of the literature[1] published in the BMJ, Drs Vinay Prasad (Oregon Health Sciences University, Portland) and David Newman (School of Medicine at Mount Sinai, New York), along with journalist Jeanne Lenzer, find that disease-specific mortality is a lousy surrogate for overall mortality. They report that when a screening technique does lower disease-specific death rates, which is both uncommon and of modest degree, there are no differences in overall mortality.

The authors cite three reasons why cancer screening might not reduce overall mortality:

  • Screening trials were underpowered to detect differences. I'm no statistician, but doesn't the fact that a trial requires millions of subjects to show a difference, mean there is little, if any, difference?
  • "Downstream effects of screening may negate any disease-specific gains." My translation: harm. Dr Peter Gøtzsche (Nordic Cochrane Center, Copenhagen) wrote in a commentary[2] that "screening always causes harm. Sometimes it also leads to benefits, and sometimes these benefits outweigh the harms." To understand harm resulting from screening, one need only to consider that a prostate biopsy entails sticking a needle through the rectum, or that some drugs used to treat breast cancer damage the heart.
  • Screening might not reduce overall mortality because of "off-target deaths." An illustration of this point is provided by a cohort study[3]that found a possible increased risk of suicide and cardiovascular death in men in the year after being diagnosed with prostate cancer. People die — of all sorts of causes, not just cancer.

Let's also be clear that this one paper is not an outlier. A group of Stanford researchers performed a systematic review and meta-analyses[4] of randomized trials of screening tests for 19 diseases (39 tests) where mortality is a common outcome. They found reductions in disease-specific mortality were uncommon and reductions in overall mortality were rare or nonexistent.

Drs Archie Bleyer and H Gilbert Welch (St Charles Health System, Central Oregon, Portland) reviewed Surveillance, Epidemiology, and End Results (SEER) data from 1976 through 2008 and concluded that "screening mammography has only marginally reduced the rate at which women present with advanced cancer and that overdiagnosis may account for nearly a third of all new breast cancer cases."[5] Likewise, a Cochrane Database Systematic review[6] of eight trials and 600,000 women did not find an effect of screening on either breast cancer mortality or all-cause mortality. This evidence caused the Swiss medical board to abolish screening mammography.[7]

These are the data. It's now clear to me that mass cancer screening does not save lives. But I'm still trying to understand how this practice became entrenched as public-health gospel. It has to be more than fear. Dr Gerd Gigerenzer (Max Planck Institute, Berlin, Germany)...He pointed to language and the ability of words to persuade. Instead of saying "early detection," advocates might use the term "prevention." This, Dr Gigerenzer says, wrongly suggests screening reduces the odds of getting cancer. Doesn't looking for cancer increase the odds of getting the diagnosis of cancer?

Gigerenzer noted two other ways language is used to emphasize screening benefits over harms: -The reporting of benefits in relative, not absolute terms. - The equating of increases in 5-year survival rates with decreases in mortality. I would add to this list of word misuse, the practice of referring to women sent to mammography screening as patients. They are not patients; they are well people. Dr Gigerenzer agreed with the commonsense notion that overall mortality should be reported along with cancer-specific mortality. His editorial included a fact box on breast cancer early detection using mammography provided by the Harding Center for Risk Literacy. I challenge you to tell me why such text boxes should not be shown to people before they undergo screening,

The first action healthcare experts should take is to spread the word that there is nothing about the mass screening of healthy people for cancer that equates to health maintenance. Embrace clear language. Saying or implying that screening saves lives when there are no data to support it and lots to refute it undermines trust in the medical profession.

The second action healthcare experts should take is to stop wasting money on screening. If the evidence shows no difference in overall mortality, why pay for it? I'm not naive to the fact that use of clear language will decrease the number of billable procedures. I am not saying this will be easy. One first move that would be less painful would be to get rid of quality measures or incentives that promote screening.

I want to be clear; I'm not saying all cancer screening is worthless. People at higher baseline risk for cancer, such as those with a family history of cancer or environmental exposures, might derive more benefit than harm from screening. Prasad, Lenzer, and Newman say this group of patients would be a good place to spend future research dollars. That sounds reasonable. I also acknowledge that some people, even when presented with the evidence, will want to proceed with screening. We can argue about who should pay for non–evidence-based medical procedures.

Published on Leave a comment on Rethinking Cancer Screening

A provocative and thought-provoking article in which the title says it all: Cancer screening has not been shown to 'save lives'. The following is from the Medscape analysis/reporting of the original British Medical Journal article and accompanying editorial ( BMJ. January 2016, Article, Editorial), and both the original and Medscape analysis are well worth reading. From Medscape:

Cancer Screening Has Not Been Shown to 'Save Lives'

Debates about cancer screening programs tend to focus on when to start, who to screen, and the frequency of screening. But some investigators are asking a far more provocative question: Do screening programs actually save lives?

We do not know the answer to that question, and would need to conduct massive clinical trials to find out, said Vinay K. Prasad, MD, MPH, assistant professor of medicine at the Oregon Health Sciences University in Portland."Proponents of cancer screening say that screening tests have been shown to save lives. What we're trying to show is that, strictly speaking, that's sort of an overstatement," he told Medscape Medical News.

In an analysis published online January 6 in the BMJ, Dr Prasad and his colleagues argue that although cancer screening might reduce cancer-specific mortality, it has not conclusively been shown to have an effect on overall mortality. The researchers go on to suggest that the harms of screening might actually contribute to overall mortality rates. These potential harms include false-positive results that lead to unnecessary biopsies or therapeutic interventions and overdiagnosis, in which treatment is delivered for a condition that is unlikely to affect patients during their natural lifespans.

"There are two chief reasons why cancer screening might reduce disease-specific mortality without significantly reducing overall mortality," the researchers write. "Firstly, studies may be underpowered to detect a small overall mortality benefit. Secondly, disease-specific mortality reductions may be offset by deaths due to the downstream effects of screening." "The bar to say that screening saves lives should be overall mortality, and we haven't met that bar," Dr Prasad told Medscape Medical News.

The rationale for cancer screening is based on the assumptions that screening will reduce deaths from cancer and that lowering cancer-specific deaths will decrease overall mortality. These assumptions remain unsupported by facts, Dr Prasad's team contends.

They illustrate this point with data from the National Lung Cancer Screening Trial (NLST). Although there was a 20% relative reduction in lung cancer deaths with low-dose CT screening, compared with chest x-ray, and a 6.7% relative reduction in overall mortality, the absolute reduction in risk for overall mortality was just 0.46%....The team also notes that "the benefit in lung cancer mortality of CT screening (estimated to avert over 12,000 lung cancer deaths in the United States annually) must be set against the 27,034 major complications (such as lung collapse, heart attack, stroke, and death) that follow a positive screening test."

The decision to undergo screening should be part of an informed discussion between the patient and clinician that takes into account personal preferences and the risks and benefits of screening. Dr Prasad explained. "Declining screening may be a reasonable and prudent choice for many people," the researchers write. "Doctors should be comfortable with whatever choice people make when they hear about all the potential benefits and the known harms," Dr Prasad added.

However, in an accompanying editorial, Gerd Gigerenzer, PhD, from the Max Planck Institute for Human Development in Berlin, argues that "rather than pouring resources into 'megatrials' with a small chance of detecting a minimal overall mortality reduction, at the additional cost of harming large numbers of patients, we should invest in transparent information in the first place." He explains that information about screening should be presented in a "fact box" that lays out the benefits and risks of mammography with numbers for how many women would be affected."It is time to change communication about cancer screening from dodgy persuasion into something straightforward," he concludes.

Richard L. Schilsky, MD, chief medical officer for the American Society of Clinical Oncology (ASCO), said that although, in general, ASCO supports cancer screening, "it's a very imperfect process....The often high variability in the natural history of many cancers has been the source of particular confusion and uncertainty surrounding screening, he noted. For example, there is little value in screening for aggressive cancers for which interventions are unlikely to make a difference in outcomes, no matter how early the disease can be detected. Conversely, "if the cancer is never going to kill you, no matter what the doctors do, then screening won't help either," he said. Additionally, there are some cancers for which treatments are sufficiently effective that they can be successfully managed whether they are diagnosed at an early or later stage. "When you consider all these factors, the number of individuals who will actually benefit from detecting a screen-detected cancer is very small," Dr Schilsky said.

Published on Leave a comment on Higher Leukemia Risk With Lower Levels of Sunshine and Vitamin D?

 The following research finds a link (it doesn't establish cause) - but these interesting associations with vitamin D keep popping up. The research looked at leukemia rates in 172 countries and found that living closer to the equator (and assumed to have higher levels of vitamin D due to sunlight exposure) is linked to lower levels of leukemia. By far the best source of vitamin D is sunshine (and not food). From Medical Xpress:

Researchers link higher risk of leukemia to low sunlight and vitamin D

Epidemiologists at University of California, San Diego School of Medicine report that persons residing at higher latitudes, with lower sunlight/ultraviolet B (UVB) exposure and greater prevalence of vitamin D deficiency, are at least two times at greater risk of developing leukemia than equatorial populations.

These results suggest that much of the burden of leukemia worldwide is due to the epidemic of vitamin D deficiency we are experiencing in winter in populations distant from the equator," said Cedric Garland, DrPH, adjunct professor in the Department of Family Medicine and Public Health and member of Moores Cancer Center at UC San Diego Health. "People who live in areas with low solar ultraviolet B exposure tend to have low levels of vitamin D metabolites in their blood," Garland said. "These low levels place them at high risk of certain cancers, including leukemia."

According to the American Cancer Society, 54,270 cases and 24,450 deaths from leukemia occur in the United States alone each year. There is no known way to prevent most types of leukemia, though some types may be prevented by avoiding high doses of ionizing radiation, exposure to the chemical benzene, smoking and certain types of chemotherapy.

The UC San Diego study analyzed age-adjusted incidence rates of leukemia in 172 countries from GLOBOCAN, an international agency for research on cancer that is part of the World Health Organization, comparing that information with cloud cover data from the International Satellite Cloud Climatology Project. The study follows similar investigations by Garland and colleagues of other cancers, including breast, colon, pancreas, bladder and multiple myeloma. In each study, they found that reduced UVB radiation exposure and lower vitamin D levels were associated with higher risks of cancer.

Leukemia rates were highest in countries relatively closer to the poles, such as Australia, New Zealand, Chile, Ireland, Canada and the United States. They were lowest in countries closer to the equator, such as Bolivia, Samoa, Madagascar and Nigeria.