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 Get active, really active, to reduce your risk for 5 diseases: breast cancer, colon cancer, heart disease, and ischemic stroke. Instead of the 150 minutes of brisk walking or 75 minutes per week of running (which is equal to the 600 metabolic equivalent (MET) minutes now recommended by the World Health Organization), this study found that much more exercise is needed for best health results.

This study (which was a review and analysis of 174 studies) found that there is a dose-response effect, with the most reduction in the risk of the 5 conditions by getting 3000 to 4000 MET minutes per week. This sounds like a lot, but the researchers  point out that this can be achieved by incorporating exercise into your daily routines. The researchers write: "A person can achieve 3000 MET minutes/week by incorporating different types of physical activity into the daily routine—for example, climbing stairs 10 minutes, vacuuming 15 minutes, gardening 20 minutes, running 20 minutes, and walking or cycling for transportation 25 minutes on a daily basis would together achieve about 3000 MET minutes a week."

So start thinking creatively about how to increase exercise or activity into your daily life, especially moderate or vigorous intensity activity. For example, park your car far from the store door, or better yet, bicycle or walk to the store from home. From Medscape:

Get Moving: High Physical-Activity Level Reduces Risk of 5 Diseases

High levels of physical activity can reduce the risk for five major diseases, including type 2 diabetes, new research shows. Findings from the systematic review and meta-analysis were published online ....The data, from a total 174 studies comprising 149,184,285 total person-years of follow-up, suggest that the more total regular daily physical activity one engages in — including recreation, transportation, occupational activity, and/or daily chores — the lower the risks for breast cancer, colon cancer, diabetes, ischemic heart disease, and ischemic stroke.

However, significant reductions in those conditions were seen only with total activity levels considerably higher than the minimum 600 metabolic equivalent (MET) minutes per week recommended by the World Health Organization for health benefits. That 600 METs equates to about 150 minutes/week of brisk walking or 75 minutes/week of running. (A MET is defined as the ratio of the metabolic rate during that activity to the metabolic rate when resting.) Risks of the five conditions dropped significantly with an increase in MET minutes per week from 600 to 3000 to 4000, with less additive benefit seen above that level.

For reference, the authors say, "a person can achieve 3000 MET minutes/week by incorporating different types of physical activity into the daily routine — for example, climbing stairs 10 minutes, vacuuming 15 minutes, gardening 20 minutes, running 20 minutes, and walking or cycling for transportation 25 minutes on a daily basis would together achieve about 3000 MET minutes a week." "This amount might seem a bit large, but this is about total activity across all domains of life.…For people who currently don't exercise, clinicians could encourage them to incorporate physical activity into their daily routines, [such as] turning household chores into exercise. 

Another recent meta-analysis of trials involving more than one million individuals indicated that an hour of moderate-intensity activity, such as brisk walking or cycling, offsets the health risks of 8 hours of sitting. The message that physical inactivity is a killer — leading to 5.3 million premature deaths annually worldwide, which is as many as caused by smoking and twice as many as associated with obesity, has been emerging over the past few years, with warnings that "sitting is the new smoking."

This new research is the first meta-analysis to quantify the dose-response association between total physical activity across all domains and the risk of five chronic diseases. The 174 prospective cohort studies included 35 for breast cancer, 19 for colon cancer, 55 for diabetes, 43 for ischemic heart disease, and 26 for ischemic stroke. (Some included more than one end point.)....Higher levels of total physical activity were associated with lower risks of all five outcomes.

With the development of diabetes, for example, compared with no physical activity, those with 600 MET minutes per week (the minimum recommended level of activity) had a 2% lower risk. That risk reduction jumped by an additional 19% with an increase from 600 to 3600 METs/week. Gains were smaller above that, with the increase of total activity from 9000 to 12,000 MET minutes/week yielding only an additional 0.6% diabetes reduction.

Overall, compared with insufficiently active individuals (total activity < 600 MET minutes/week), the risk reduction for those in the highly active category (≥ 8000 MET minutes/week) was 14% for breast cancer; 21% for colon cancer; 28% for diabetes; 25% for ischemic heart disease; and 26% for ischemic stroke

 Credit: Medscape

 A medical article in the journal Addiction states that there is strong evidence that alcohol causes 7 cancers, that there is evidence that it probably causes more, the effects are dose related, and if one also smokes the risks are greatly increased. The 7 cancers are: oropharynx (mouth and pharynx), larynx, esophagus, liver, colon, rectum, and female breast. An earlier post reported on conflicting results from some studies (e.g. that low to moderate alcohol consumption is beneficial), as well as the finding that effects are dose-related (the more alcohol a person drinks, the higher the risk of cancer). NOTE: One standard drink contains 10 grams of alcohol, and is equivalent to one ordinary beer, a small glass of wine (100 mls or 5 oz) or a nip of spirits (30 mls). The article excerpts below state that the strongest effects are from consuming 50 grams or more of alcohol per day (compared to those who don't drink at all). From Medscape:

No Confusion: Alcohol Causes Seven Cancers

There is "strong evidence" that alcohol causes seven cancers, and other evidence indicates that it "probably" causes more, according to a new literature review published online July 21 in Addiction. Epidemiologic evidence supports a causal association of alcohol consumption and cancers of the oropharynx, larynx, esophagus, liver, colon, rectum, and female breast, says Jennie Connor, MB, ChB, MPH, from the Department of Preventive and Social Medicine, University of Otago, in Dunegin, New Zealand.

In short, alcohol causes cancer. This is not news, says Dr Connor. The International Agency for Research on Cancer (IARC) and other agencies have long identified alcohol consumption as being causally associated with these seven cancers. So why did Dr Connor, who is an epidemiologist and physician, write a new review? Because she wants to "clarify the strength of the evidence" in an "accessible way." 

The newly published review "reinforces the need for the public to be made aware of the causal link between alcohol and cancer," said Colin Shevills, from the Alcohol Health Alliance UK, in a press statement....The lack of clarity about alcohol causing cancer, Dr Connor believes, is related to alcohol industry propaganda as well as the fact that the "epidemiological basis for causal inference is an iterative process that is never completed fully."

Dr Connor writes that the strength of the association of alcohol as a cause of cancer varies by bodily site. The evidence is "particularly strong" for cancer of the mouth, pharynx, and esophagus (relative risk, ~4-7 for ≥50 g/day of alcohol compared with no drinking) but is less so for colorectal cancer and liver and breast cancer (relative risk, ~1.5 for ≥50 g/day). "For cancers of the mouth, pharynx, larynx and oesophagus there is a well-recognized interaction of alcohol with smoking, resulting a multiplicative effect on risk," adds Dr Connor.

Other cancers are also likely caused by alcohol. Dr Connor writes that there is "accumulating research" supporting a causal contribution of alcohol to cancer of the pancreas, prostate, and skin (melanoma). One British expert had an opinion about alcohol's carcinogenicity. In a statement about the new review, Prof Dorothy Bennett, director of the Molecular and Clinical Sciences Research Institute at St. George's, University of London, said: "Alcohol enters cells very easily, and is then converted into acetaldehyde, which can damage DNA and is a known carcinogen."

In the new review, Dr Connor describes various hallmarks of causality that have been found in epidemiologic studies of alcohol and these seven cancers, such as a dose-response relationship and the fact that the risk for some of these cancers (esophageal, head and neck, and liver) attenuates when drinking ceases. Current estimates suggest that alcohol-attributable cancers at the seven cancer sites make up 5.8% of all cancer deaths worldwide, she states. The alcohol industry has a lot at stake, she says, which in turn leads to "misinformation" that "undermines research findings and contradicts evidence-based public health messages."

But there is no safe level of drinking with respect to cancer, says Dr Connor, citing research about low to moderate levels of alcohol, which has been covered by Medscape Medical News. This was also the conclusion of the 2014 World Cancer Report, issued by the World Health Organization's IARC.

 Amazing!  Researchers found that the bacteria found in breast cancer patients and healthy patients are different. (See post on their earlier work on breast microbiome.) And not only that, but the types of bacteria (Lactobacillus and Streptococcus) that are more prevalent in the breasts of healthy women are considered "beneficial" and may actually protect them from breast cancer. Meanwhile, elevated levels of the bacteria Escherichia coli and Staphylococcus epidermidis found in the breast tissue adjacent to tumors are the kind that do harm (e.g., known to induce double-stranded breaks in DNA) . This research raises the question: could probiotics (beneficial bacteria) protect breasts from cancer? From Science Daily:

Beneficial bacteria may protect breasts from cancer

Bacteria that have the potential to abet breast cancer are present in the breasts of cancer patients, while beneficial bacteria are more abundant in healthy breasts, where they may actually be protecting women from cancer, according to Gregor Reid, PhD, and his collaborators. These findings may lead ultimately to the use of probiotics to protect women against breast cancer. The research is published in the ahead of print June 24 in Applied and Environmental Microbiology, a journal of the American Society for Microbiology.

In the study, Reid's PhD student Camilla Urbaniak obtained breast tissues from 58 women who were undergoing lumpectomies or mastectomies for either benign (13 women) or cancerous (45 women) tumors, as well as from 23 healthy women who had undergone breast reductions or enhancements. They used DNA sequencing to identify bacteria from the tissues, and culturing to confirm that the organisms were alive. 

Women with breast cancer had elevated levels of Escherichia coli and Staphylococcus epidermidis, are known to induce double-stranded breaks in DNA in HeLa cells, which are cultured human cells. "Double-strand breaks are the most detrimental type of DNA damage and are caused by genotoxins, reactive oxygen species, and ionizing radiation," the investigators write. The repair mechanism for double-stranded breaks is highly error prone, and such errors can lead to cancer's development.

Conversely, Lactobacillus and Streptococcus, considered to be health-promoting bacteria, were more prevalent in healthy breasts than in cancerous ones. Both groups have anticarcinogenic properties. For example, natural killer cells are critical to controlling growth of tumors, and a low level of these immune cells is associated with increased incidence of breast cancer. Streptococcus thermophilus produces anti-oxidants that neutralize reactive oxygen species, which can cause DNA damage, and thus, cancer.

The motivation for the research was the knowledge that breast cancer decreases with breast feeding, said Reid. "Since human milk contains beneficial bacteria, we wondered if they might be playing a role in lowering the risk of cancer. Or, could other bacterial types influence cancer formation in the mammary gland in women who had never lactated? To even explore the question, we needed first to show that bacteria are indeed present in breast tissue." (They had showed that in earlier research.)

But lactation might not even be necessary to improve the bacterial flora of breasts. "Colleagues in Spain have shown that probiotic lactobacilli ingested by women can reach the mammary gland," said Reid. "Combined with our work, this raises the question, should women, especially those at risk for breast cancer, take probiotic lactobacilli to increase the proportion of beneficial bacteria in the breast? To date, researchers have not even considered such questions, and indeed some have balked at there being any link between bacteria and breast cancer or health."

Besides fighting cancer directly, it might be possible to increase the abundance of beneficial bacteria at the expense of harmful ones, through probiotics, said Reid. Antibiotics targeting bacteria that abet cancer might be another option for improving breast cancer management, said Reid. In any case, something keeps bacteria in check on and in the breasts, as it does throughout the rest of the body, said Reid. "What if that something was other bacteria--in conjunction with the host immune system?

Surprising results (to me at least) from research comparing various diets and incidence of several cancers in 11,082 individuals in the Netherlands over a 20 year period. I expected the daily meat eaters to have higher rates of the 3 cancers studied, but no....

Their main conclusion: vegetarians, pescetarians (no meat, but does eat fish), and low-meat consumers did not have a reduced risk of lung, postmenopausal breast, and overall prostate cancer when compared with individuals consuming meat on a daily basis. This is after taking confounders such as smoking into account (because smokers have higher rates of cancers such as lung cancer). The researchers do point out that some other similar studies had mixed results, but that perhaps those studies did not take confounders (variables that distort the results) such as smoking, physical activity levels, alcohol consumption, etc. into account. From the European Journal of Clinical Nutrition:

Vegetarianism, low meat consumption and the risk of lung, postmenopausal breast and prostate cancer in a population-based cohort study

The few prospective studies that examined lung, female breast and prostate cancer risk in vegetarians have yielded mixed results, whereas none have studied the effects of low meat diets. Moreover, little is known about the explanatory role of (non-) dietary factors associated with these diets.The Netherlands Cohort Study—Meat Investigation Cohort (NLCS-MIC)— is an analytical cohort of 11,082 individuals including 1133 self-reported vegetarians (aged 55–69 years at baseline). At baseline (1986), subjects completed a questionnaire on dietary habits and other risk factors for cancer and were classified into vegetarians (n=691), pescetarians (n=389), 1 day per week (n=1388), 2–5 days per week (n=2965) and 6–7 days per week meat consumers (n=5649).

After 20.3 years of follow-up, 279 lung, 312 postmenopausal breast and 399 prostate cancer cases (including 136 advanced) were available for analyses. After adjustment for confounding variables, we found no statistically significant association between meat consumption groups and the risk of lung cancer. As well, no significant associations were observed for postmenopausal breast and overall prostate cancer. After adjustment for confounders, individuals consuming meat 1 day per week were at a 75% increased risk of advanced prostate cancer compared with 6–7 days per week meat consumers.

Vegetarians, pescetarians and 1 day per week meat consumers did not have a reduced risk of lung, postmenopausal breast and overall prostate cancer compared with individuals consuming meat on a daily basis after taking confounders into account.

Although vegetarian diets are primarily defined by the absence of meat and fish, they are also shown to be associated with high intakes of fruits and vegetables and a favorable distribution of non-dietary factors.1, 2 Consequently, vegetarian diets may reduce the risk of different types of cancers through multiple mechanisms, depending on the etiology and preventability of the tumor.3, 4

We previously reported a nonsignificantly reduced risk of vegetarian and low meat diets on colorectal, and especially rectal, cancer5 and set out to study its effect on three other major cancers. Although meat consumption has been hypothesized to be implicated in the etiology of lung, female breast and prostate cancer, data are not consistent across studies and meat subtypes.6, 7, 8However, on the basis of the existing body of literature, vegetarians may be at a lower risk of developing lung cancer (because of lower smoking rates) and to postmenopausal breast cancer (because of lower alcohol consumption, lower body mass index and higher physical activity levels).

Results from this prospective cohort study showed that, in age- and sex-adjusted models, vegetarians and pescetarians were at a reduced risk of lung cancer compared with individuals consuming meat on a daily basis. This effect disappeared after taking confounders, especially smoking, into account. We did not observe an association between the meat consumption group and the risk of post-menopausal breast and overall prostate cancer.

Our null findings regarding post-menopausal breast cancer risk are in line with other prospective studies comparing vegetarians with non-vegetarians and a pooled analysis of five cohort studies on breast cancer mortality. In contrast, the UK Women’s Cohort Study reported a lower post-menopausal breast cancer risk among non-meat consumers compared with high meat consumers,14 although this was not observed in their dietary pattern analyses.15 Vegetarian diets are rich in fiber and soy. Fiber was associated with a reduced risk of breast cancer in a meta-analysis of prospective studies,19 and soy contains isoflavones, which have previously been associated with a significant reduced risk of postmenopausal breast cancer in Asian populations.20 However, compared with the average soy intake in four Asian countries (ranging from 38 to 134 g/day21), the soy product intake among vegetarians in our population was likely too low to exert an effect (~15g per day).

 A recent study pooled the data from over a million Europeans and Americans and found that higher levels of leisure-time physical activity was associated with a reduced risk of developing cancer in 13 of the 26 cancers looked at. For that group of 13 cancers, the cancer risk reduction ranged from 10% to 42%. And most of these associations (leisure-time physical activity and lower risk of cancer) were evident regardless of body size or smoking history. Bottom line: getting active may lower your cancer risk. From Science Daily:

Physical activity associated with lower risk for many cancers

Higher levels of leisure-time physical activity were associated with lower risks for 13 types of cancers, according to a new study published online by JAMA Internal Medicine. Physical inactivity is common, with an estimated 51 percent of people in the United States and 31 percent of people worldwide not meeting recommended physical activity levels. Any decrease in cancer risk associated with physical activity could be relevant to public health and cancer prevention efforts.

Steven C. Moore, Ph.D., M.P.H., of the National Cancer Institute, Bethesda, Md., and coauthors pooled data from 12 U.S. and European cohorts (groups of study participants) with self-reported physical activity (1987-2004). They analyzed associations of physical activity with the incidence of 26 kinds of cancer.The study included 1.4 million participants and 186,932 cancers were identified during a median of 11 years of follow-up.

The authors report that higher levels of physical activity compared to lower levels were associated with lower risks of 13 of 26 cancers: esophageal adenocarcinoma (42 percent lower risk); liver (27 percent lower risk); lung (26 percent lower risk); kidney (23 percent lower risk); gastric cardia (22 percent lower risk); endometrial (21 percent lower risk); myeloid leukemia (20 percent lower risk); myeloma (17 percent lower risk); colon (16 percent lower risk); head and neck (15 percent lower risk), rectal (13 percent lower risk); bladder (13 percent lower risk); and breast (10 percent lower risk). Most of the associations remained regardless of body size or smoking history, according to the article. Overall, a higher level of physical activity was associated with a 7 percent lower risk of total cancer.

Physical activity was associated with a 5 percent higher risk of prostate cancer and a 27 percent higher risk of malignant melanoma, an association that was significant in regions of the U.S. with higher levels of solar UV radiation but not in regions with lower levels, the results showed.

The authors note the main limitation of their study is that they cannot fully exclude the possibility that diet, smoking and other factors may affect the results. Also, the study used self-reported physical activity, which can mean errors in recall."These findings support promoting physical activity as a key component of population-wide cancer prevention and control efforts," the authors conclude.

 For the first time ever, one type of cancer has been reclassified as a non-cancer. An international panel of pathologists and clinicians has reclassified a type of thyroid cancer to reflect that it is noninvasive and has a low risk for recurrence.The panel renamed encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC) as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). There has been concern for a while of the costs (financial, physical, and mental) of the overdiagnosis and overtreatment for something that won't spread (it's "indolent" and "low-risk").

There have been discussions for some time now in the medical community regarding the move away from the word "cancer" in the description of early stages of both breast and prostate cancer. In 2013, a medical team sanctioned by the National Cancer Institute proposed that a number of premalignant conditions, including ductal carcinoma in situ and high-grade prostatic intraepithelial neoplasia, should no longer be called "cancer." Instead, the conditions should be labeled something more appropriate, such as indolent lesions of epithelial origin (IDLE), the group suggested. " Use of the term 'cancer' should be reserved for describing lesions with a reasonable likelihood of lethal progression if left untreated," the group said at the time.

From Futurity: NONINVASIVE THYROID ‘CANCER’ ISN’T CANCER

The reclassification of a noninvasive type of thyroid cancer that has a low risk of recurrence is expected to reduce the fears and the unnecessary interventions that come with a cancer diagnosis, experts say. The incidence of thyroid cancer has been rising partly due to early detection of tumors that are indolent or non-progressing, despite the presence of certain cellular abnormalities that are traditionally considered cancerous, says senior investigator Yuri Nikiforov, professor of pathology at the University of Pittsburgh.

“This phenomenon is known as overdiagnosis,” Nikiforov says. “To my knowledge, this is the first time in the modern era a type of cancer is being reclassified as a non-cancer. I hope that it will set an example for other expert groups to address nomenclature of various cancer types that have indolent behavior to prevent inappropriate and costly treatment.”

In particular, a tumor type known as encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC) has increased in incidence by an estimated two- to three-fold over the past 20 to 30 years and makes up 10 to 20 percent of all thyroid cancers diagnosed in Europe and North America. Although studies have shown EFVPTC is not dangerous, it is typically treated as aggressively as other types of thyroid cancer. At the recommendation of the National Cancer Institute, the panel sought to revise the terminology and to see if the word “cancer” could be dropped from its name.

As reported in JAMA Oncology, two dozen experienced pathologists from seven countries and four continents independently reviewed 268 tumor samples diagnosed as EFVPTC from 13 institutions....In a group of more than 100 noninvasive EFVPTCs, there were no recurrences or other manifestations of the disease at a median follow-up of 13 years. They decided to rename EFVPTC as “noninvasive follicular thyroid neoplasm with papillary-like nuclear featuresor NIFTP. The new name cites key features to guide pathologists in diagnosis, but omits the word “cancer,” indicating that it need not be treated with radioiodine or other aggressive approaches.

“We determined that if NIFTP is carefully diagnosed, the tumor’s recurrence rate is extremely low, likely less than 1 percent within the first 15 years,” Nikiforov says. “The cost of treating thyroid cancer in 2013 was estimated to exceed $1.6 billion in the US. Not only does the reclassification eliminate the psychological impact of the diagnosis of ‘cancer,’ it reduces the likelihood of complications of total thyroid removal, and the overall cost of health care.”

 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.

 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.

 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.

 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.