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Category: breast cancer

Published on Leave a comment on Viewing Cancers As Birds, Rabbits, and Turtles

This article by academic physician and cancer researcher H. Gilbert Welch about viewing cancers as a barnyard pen of animals (birds, rabbits, and turtles) is a way to explain why some early screening tests haven't really reduced the rate of deaths from certain cancers, such as breast cancer (here and here). Or another way of looking at it is that some cancers are really "bad" and aggressive (birds that have already flown away to distant points at earliest cancer diagnosis), while others are "good" (rabbits or cancers that are slowly spreading and that can be treated, or turtles - that are such slow growing cancers that they would never cause a problem).

Interesting and thought-provoking reading. Excerpts from an editorial by H.Gilbert Welch from Breast Cancer Research and Treatment:

The heterogeneity of cancer

Cancer used to be so simple. It started as a wayward cell that then underwent a stepwise progression: from in situ to local, local to regional and, finally, regional to distant disease. At least, that is what I was taught in medical school…some (gulp) 40 years ago. Narod and Sopik suggest a wildly different paradigm. Local growth and distant metastasis are independent phenomena. Local control of cancer (e.g., efforts to minimize local recurrence) has no effect on its tendency to metastasize. If a cancer is destined to spread to distant sites, it will have already done so.

Call it the “bad cancers are bad” model. Or, alternatively, “good cancers are good.” Oddly enough, in 1955 a cancer surgeon at the Cleveland clinic—George Crile Jr.—foretold this complexity on the pages of Life magazine: In clinical practice to say that a person has cancer gives as little information about the possible course of his disease as to say that he has an infection. There are dangerous infections that may be fatal and there are harmless infections that are self-limited or may disappear. The same is true of cancers. Cancer is not a single entity. It is a broad spectrum of diseases related to each other only in name. 

..... The conventional model has been that large tumors are more likely to metastasize because they have a large pool of cancer cells to disseminate. Narod and Sopik instead suggest that these tumors became large because they are more aggressive cancers and thus are more likely to metastasize. Large, late-stage, node positive lesions are simply valuable markers for “badness.” The corollary is that small, early-stage, node negative lesions are valuable markers for “goodness.” But not always.

Which brings us to the conundrum of DCIS. It would be simplest if all DCIS was pseudodisease— cancer not destined to ever cause problems for our patients. Most DCIS is pseudodisease, but as Narod documented in earlier work , about 3% of women with DCIS will die from breast cancer in the next 20 years. Over half of these women did not experience an in-breast invasive recurrence prior to death. In other words, bad breast cancers are bad—from the get go.

This phenomenon explains the limited ability of mammography to reduce breast cancer mortality. The lack of value in finding microscopic breast cancers (like DCIS) is one of the least well-recognized findings from the ten randomized trials of mammography. Only one trial addressed this important question, the second Canadian trial ..... Given the finding of no difference in breast cancer mortality between the two groups, the lesson is clear: there is no obvious value to finding breast cancers that are so small they cannot be felt (such as most DCIS).

Overdiagnosis is made possible by cancers at the other end of the spectrum. Overdiagnosis is the detection of cancers that are very good – so good that patients would be better of not having them detected. Overdiagnosis doesn’t limit the ability of mammography to reduce breast cancer mortality—instead it’s a side-effect of the effort.

Such heterogeneity in cancer poses huge challenges for our effort to catch the disease early. It’s been described as the “barnyard pen of cancers” (an analogy that likely originates with Crile). We are trying to catch birds, rabbits, and turtles.

We can’t catch the birds early, because they have already gone—these are the most aggressive cancers, those that have already spread by the time they are detectable. We are able to catch the rabbits—the more slowly progressive cancers— but their earlier detection may not help much, because they weren’t destined to metastasize anyway. And then there are the turtles. There’s no need catch them, because they’re not going anywhere anyway.

Published on Leave a comment on Too Much Cancer Screening Has Misled Us About Risk Factors?

H. Gilbert Welch has written extensively about the issue of "overdiagnosis" and resulting  "overtreatment" of cancers. Cancer screening can cause the problem of overdiagnosis (finding small tumors that may never cause problems) and lead to overtreatment (treating unnecessarily, which can cause harm).

But now Welch and coauthor Otis Brawley discuss the issue of how too much screening and diagnostic testing of people thought to be "high risk"  for certain cancers results in more being found - thus the risk factors are "self-fulfilling". And it occurs the most in "scrutiny dependent cancers" - which are cancers that the more you look, the more you find, and the more of what you find is harmless. Many are referred to as slow-growing, indolent, subclinical, or even as precancerous. Prostate cancer, thyroid cancer, breast cancer, melanoma, and  lung cancer are  examples of "scrutiny-dependent" cancers.

Looking so hard and then finding cancer gives a false impression of an increased incidence of some cancers. The authors also said that risk factors in determining  who should be screened should not be cancer diagnosis (e.g. in a family member), but death from cancer. From STAT News:

Too much screening has misled us about real cancer risk factors, experts say

The best-known downside of cancer screening, such as PSA tests for prostate cancer and mammograms for breast cancer, is that they often flag cancers that pose no risk, leading to overdiagnosis and unnecessary, even harmful, treatment. But widespread screening for “scrutiny-dependent” cancers — those for which the harder you look the more you find, and the more of what you find is harmless — causes another problem, two leading cancer experts argue in a paper published on Monday: increasing the apparent incidence of some cancers. That in turn is misleading doctors and the public about what increases people’s risk of developing cancers — or at least the types of cancer that matter.

“Detecting cancers that would never become apparent is screwing up our understanding of risk factors,” said Dr. H. Gilbert Welch of the Dartmouth Institute for Health Policy and Clinical Practice, co-author of the analysis in Annals of Internal Medicine. The problem is especially clear in prostate, breast, and thyroid cancers, all of which are scrutiny dependent.

Men whose relatives developed prostate cancer are more likely to get PSA and other screening tests, either because they request them or because their physicians, noting their family histories, order them. Men with no such family history are less likely to be screened. .... (More than half of such cancers are so slow-growing that they don’t affect health or longevity.) Men who don’t get screened are less likely to have biopsies and so are less likely to be diagnosed with prostate cancer — not because they develop the disease at a lower rate but because they get screened at a lower rate. What you don’t look for, you don’t find.

“If we biopsied men without a family history of prostate cancer at the same rate that we biopsy men with a family history, we’d find more prostate cancer in them as well,” Welch said. “Family history influences how hard we look for prostate cancer and therefore how much we find. The risk factor becomes a self-fulfilling prophecy.”

A 2016 study of increased prostate cancer screening in men with a family history of the disease concluded that the risk due to family history has been overestimated by nearly half. “The risk factor of family history is spuriously strengthened because men with a family history are exposed to greater scrutiny,” write Welch and Dr. Otis Brawley, chief medical officer of the American Cancer Society, in the Annals report.

Wealthier, better educated women are, however, more connected to the health care system and therefore get more mammograms, breast ultrasounds, and MRIs. The more scrutiny, the more likely that harmless cases of breast cancer are found. (The idea of “harmless” breast cancer sounds like an oxymoron, but an estimated one-half of breast cancers detected by screening would never cause problems even if undetected and untreated.)

Breast tumors found by imaging are much more likely to be harmless than those discovered by women or their physicians finding a breast lump. Income and education are therefore less likely to be a true risk factor for breast cancer and more likely to be a “risk factor” for undergoing screening. If poorer, less educated women were screened for breast cancer at the same rate as wealthier, better educated women, the socioeconomic risk factor would likely vanish.

Thyroid cancers are also scrutiny dependent, which is why when countries launch screening programs the incidence of the disease skyrockets (but death rates don’t, showing that what’s being found is a false epidemic). 

Welch and Brawley call for less focus on risk factors for developing cancers, since those numbers both determine and reflect who gets screened, and more on risk factors for death from cancer.

Published on Leave a comment on Is Eating A Mediterranean Diet Protective Against Aggressive Prostate Cancer?

Prostate cancer is something that men worry about, especially because it is the most common cancer in men, and because it can take several forms. On one hand, a tumor can be "indolent" or so slow growing that it just needs to be monitored, or sometimes it can be very aggressive and even lead to death. That's why the possibility of a dietary pattern (what a person eats) having an effect on the cancer's progression or aggressiveness is very exciting - if true, it would be something people could do to improve their prostate cancer outcome. Or perhaps even prevent it in the first place. Studies up to this point have been mixed, with no clear results.

A recent large study conducted in Spain found that those men with prostate cancer who had a high adherence to a Mediterranean diet had a lower risk of aggressive prostate cancer, as compared to those following a typical Western diet (large amounts of fatty dairy products, refined grains, processed meat, caloric beverages, sweets, fast food, and sauces) or a Prudent diet (low-fat dairy products, whole grains, fruits, vegetables, and juices). A Mediterranean dietary pattern is rich in fruits and vegetables, and also fish, legumes, boiled potatoes, olives and olive oil, vegetable oils, and a low intake of juices.

The researchers also discussed that there are many similarities with breast cancer and prostate cancer, including risk factors. They found in an earlier study in Spain that eating a Western diet is associated with breast cancer risk, the Prudent diet is not associated with breast cancer, and the Mediterranean diet seems to be protective for breast cancer. From Medical Xpress:

A more complete Mediterranean diet may protect against aggressive prostate cancer

In a new study published in The Journal of Urology, researchers determined that men who followed a Mediterranean diet, rich in fish, boiled potatoes, whole fruits, vegetables, legumes, and olive oil, and low consumption of juices had lower risk of aggressive prostate cancer (PC) than those who followed other dietary patterns like Prudent or Western diets. ..."Our results show that a diet oriented towards the prevention of aggressive tumors in the prostate should probably include important elements of the Mediterranean diet such as fish, legumes, and olive oil, and suggest that a high intake of fruits, vegetables, and whole grains might not be enough."

The authors explored the relationship between the risk of having PC and dietary patterns as part of the MCC-Spain study, a Spanish case-control study that involved 733 patients with histologically confirmed PC and 1,229 healthy men with a mean age of 66 years from seven Spanish regions. Anthropometric, epidemiologic, and dietary data were collected.

Adherence to the three dietary patterns of Western, Prudent, and Mediterranean, which characterize the dietary habits of the Spanish population, was evaluated, The Western [dietary] pattern includes consumption of large amounts of fatty dairy products, refined grains, processed meat, caloric beverages, sweets, fast food, and sauces. The Prudent pattern involves consumption of low-fat dairy products, whole grains, fruits, vegetables, and juices. Finally, the Mediterranean pattern consists of high consumption of fish, boiled potatoes, fruits, vegetables, legumes, and olive oil, and low consumption of juices. The diets were graded according to the degree of adherence to each pattern and assigned to four quartiles from lower to higher adherence within each pattern.

Only a high adherence to Mediterranean dietary pattern appeared to be associated with a lower risk of aggressive PC. Prudent and Mediterranean dietary patterns showed different effects in low and high grade tumors. 

PC was assessed using Gleason scores of tumor aggressiveness (<6 or ?6) and clinical stage (cT1b to cT4). A Gleason score of <6 typically indicates a less aggressive tumor with generally good prognosis. Lower clinical stage (cT1-cT2a) indicates a tumor that has not spread. Results indicated that for more aggressive and more extensive tumors (Gleason >6 and stages cT2b to cT4), only high adherence to the Mediterranean diet showed a statistically significant protective effect. All other dietary patterns and tumor characteristics showed little or no correlation and did not achieve statistical significance. [Original study.]

Published on Leave a comment on Slight Increased Risk of Breast Cancer From Low Dose Hormonal Birth Control

 The findings of a large study from Denmark were a disappointment for those hoping that women taking or using low dose hormonal birth control (pills, IUD) would not show an increase in breast cancer (like the old higher dose birth control pills). This study found a small increase in the risk of breast cancer with the use of modern birth control pills and with a progestin-only intrauterine device. They pointed out that the biggest risk was in those using hormonal methods for over 10 years and in their 40s (most of the breast cancer cases occurred in this group of women). The risk goes up the longer one uses hormonal contraception.

Due to smaller numbers of women using a birth control patch, vaginal ring, and implants - they were unable to say one way or another if these also are linked to a higher incidence of breast cancer. But the sense from the researchers is that all hormonal contraception has a slight increase in risk of breast cancer. How big an increase in risk? There is a 20% increased risk overall, but the actual numbers are fairly small - 13 per 100,000 women or approximately 1 extra breast cancer for every 7690 women using hormonal contraception for 1 year. From Medical Xpress:

Small risk of breast cancer seen with hormone contraceptives

Modern birth control pills that are lower in estrogen have fewer side effects than past oral contraceptives. But a large Danish study suggests that, like older pills, they still modestly raise the risk of breast cancer, especially with long-term use. Researchers found a similar breast cancer risk with the progestin-only intrauterine device, and they couldn't rule out a risk for other hormonal contraceptives like the patch and the implant.

But the overall increased risk was small, amounting to one extra case of breast cancer among 7,700 women using such contraceptives per year. Experts who reviewed the research say women should balance the news against known benefits of the pill - including lowering the risk of other cancers.

Researchers analyzed health records of 1.8 million women, ages 15 to 49, in Denmark where a national health care system allows linking up large databases of prescription histories, cancer diagnoses and other information. Results were published Wednesday in the New England Journal of Medicine. Novo Nordisk Foundation funded the research, but played no role in designing the study.

Current and recent use of hormonal contraceptives was associated with a 20 percent increased risk of breast cancer. Risk increased with longer use, from a 9 percent increase in risk with less than a year of contraceptive use to a 38 percent increase after more than 10 years of use. Digging further, the researchers found no differences among types of birth control pills. Because of fewer users, the results for the patch, vaginal ring, implant and progestin shot were less clear, but the analysis didn't rule out an increased breast cancer risk for those methods. [Original study.]

Published on Leave a comment on Hair Dyes, Hair Relaxers, and Breast Cancer

There has long been concern over the chemicals in hair dyes and chemical hair straighteners or relaxers, and whether they are linked to various cancers. Studies have had mixed findings with regard to breast cancer, but a review paper concluded that there is evidence to support a role of hair product use in the risk of early onset breast cancer, especially in African-American women. Other studies found that long term users of dark hair dyes have a significantly increased risk of non-Hodgkin's lymphoma, multiple myeloma, and bladder cancer. 

A recent study done in the New York City and New Jersey area looked at both African-American women and white women and their use of various hair chemical products. They found that regularly chemically relaxing hair or dying hair dark brown or black is associated with an elevated risk of breast cancer in both African-American and white women. And women using both types of products had an even higher risk of breast cancer.From Medscape:

Dark Hair Dye and Chemical Relaxers Linked to Breast Cancer

African-American and white women who regularly chemically straighten their hair or dye it dark brown or black have an elevated risk of breast cancer, new research suggests. The study of 4,285 African-American and white women was the first to find a significant increase in breast cancer risk among black women who used dark shades of hair dye and white women who used chemical relaxers.

Black women who reported using dark hair dye had a 51 percent increased risk of breast cancer compared to black women who did not, while white women who reported using chemical relaxers had a 74 percent increased risk of breast cancer, the study found. The risk of breast cancer was even higher for white women who regularly dyed their hair dark shades and also used chemical relaxers, and it more than doubled for white dual users compared to white women who used neither dark dye nor chemical straighteners.

The study included adult women from New York and New Jersey, surveyed from 2002 through 2008, who had been diagnosed with breast cancer, plus women of similar age and race but without a history of cancer.....While the vast majority - 88 percent - of blacks had used chemicals to relax their hair, only 5 percent of whites reported using relaxers. For dark hair dye, the numbers flipped, though the differences were not as dramatic. While 58 percent of whites said they regularly dyed their hair dark shades, only 30 percent of blacks did.

The most striking results showed increased risk in the minority of black women who used dark hair dye and white women who used chemical relaxers. Black women who used chemical straighteners and white women who used dark hair dyes were also at higher risk for breast cancer, but that might have been due to chance. James-Todd said that because so many of the black women used chemical relaxers and so many of the white women used dark hair dye, links would have been hard to detect. There’s no reason to believe that chemical relaxers and hair dyes would increase the risk for women of one race and not of another, she said. 

Previous studies have shown that long-term users of dark dyes have a four-fold increased risk of fatal non-Hodgkin’s lymphoma and fatal multiple myeloma, the authors write. Prior research also has associated dark hair dye use with an increased risk of bladder cancer. A 2016 report from the U.S. Centers for Disease Control and Prevention found that breast cancer rates are generally similar for black and white women, at around 122 new cases for every 100,000 women per year, although black women with the disease are more likely to die from it.  [Original study.]

Published on Leave a comment on Vitamin D, Breast Cancer, and Melanoma

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

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

Serum Vitamin D and Risk of Breast Cancer within Five Years

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

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

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

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

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

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

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

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Published on 1 Comment on Is Coffee From Lightly Roasted Coffee Beans Best For Health?

Should the results of this study determine what kind of coffee one drinks? Does it really make a difference? Eh...Not for me (because all coffee seems to be beneficial), but it might for you.

Studies show that daily drinking of coffee appears to have health benefits. Studies have linked coffee consumption with lower rates of cancer (here and here), cardiovascular disease, and diabetes. Coffee contains beneficial chemicals (such as caffeine and chlorogenic acid) that are antioxidant and anti-inflammatory, and could help fight chronic inflammatory diseases. It turns out that how much coffee beans are roasted changes how much chlorogenic acid they contain, but the amount of caffeine basically stays the same among the different roasting levels.

Researchers in Korea compared the caffeine and chlorogenic acid components of Arabica coffee beans at different roasting levels: Light, Medium, City, and French roast. They then tested various protective antioxidant and anti-inflammatory properties of the different coffee extracts in various "cell models" (meaning in the lab, not on real people). They found that chlorogenic acid levels were higher in light roasted coffee extract than the other roasted groups, and also light roasted coffee extract had the highest antioxidant activity. The results found that increasing degrees of roasting reduced antioxidant and anti-inflammatory activities.

From the Journal of Medicinal Food: Cellular Antioxidant and Anti-Inflammatory Effects of Coffee Extracts with Different Roasting Levels

During roasting, major changes occur in the composition and physiological effects of coffee beans. In this study, in vitro antioxidant effects and anti-inflammatory effects of Coffea arabica green coffee extracts were investigated at different roasting levels corresponding to Light, Medium, City, and French roast. Total caffeine did not show huge difference according to roasting level, but total chlorogenic acid contents were higher in light roasted coffee extract than other roasted groups. In addition, light roasted coffee extract had the highest antioxidant activity.... The expression of mRNA for tumor necrosis factor-alpha and interleukin-6 was decreased in cells treated with the coffee extracts and the expression decreased with increasing roasting levels. These data suggest that coffee has physiological antioxidant and anti-inflammatory activities and these effects are negatively correlated with roasting levels in the cell models.

Coffee is one of the most popular beverages worldwide. Increasing consumption of coffee is related to the pleasing taste and aroma, as well as its physiological effects. Coffee is proposed to exert beneficial effects against cancer, cardiovascular disease, obesity, and diabetes. Coffee contains phenolic compounds such as caffeic acid, chlorogenic acid, ferulic acid, vanillic acid, and other phytochemicals. The quality of coffee is significantly related to the roasting process.... During roasting, there are numerous changes in coffee bean compound profiles and the aroma is increased. Major changes in coffee bean composition occur during roasting as a result of the Maillard reaction..... Roasting markedly affects chlorogenic acid, leading to hydrolysis of chlorogenic acid. New compounds are formed during the roasting process; one of these is melanoidin. Its formation might alter the overall antioxidant capacity of coffee beans after roasting.

Coffee is a rich source of antioxidants that may contribute to prevention of oxidative stress-related diseases. The antioxidant properties of coffee may reflect the presence of both phenolic and nonphenolic bioactive compounds, such as caffeine and chlorogenic acids. Previous studies have shown that coffee has protective effects against oxidation and DNA damage in human cell models and has been shown to possess an in vitro antioxidant activity that lessens lipid peroxidation and neoplastic activity. 

Caffeine is the major component in coffee extract and has antioxidant property. Chlorogenic acid is another well-known efficient antioxidant in coffee extract; it was highest in Light roast coffee extract and highest with low roasting temperature and lowest in Dark roasted extract. Carbohydrates, protein, and chlorogenic acid are all decreased in coffee during the roasting process.... Caffeine contents showed no differences among roasting levels, but chlorogenic acid content decreased as roasting degree increased..... The effect of coffee roasting on the antioxidant properties of coffee extracts was investigated in several earlier studies; antioxidant capacity decreased in Dark roast coffee. The antioxidant property of coffee extracts prepared with different roasting levels was also determined in this study. The best antioxidant activity was evident in Light roast coffee extract and the lowest in French roast coffee.

Published on Leave a comment on Living In More Polluted Counties Linked To Higher Cancer Rates

This is a thought-provoking study that looked at environmental quality and cancer incidence in counties throughout the US. The researchers found that the more polluted the county, the higher the cancer incidence. An increase in cancer rates was associated with poorer air quality and the "built environment" (such as major highways). They correctly point out that many things together can contribute to cancer occurring - and this is why looking at how polluted the air, water, etc. together is important.

They looked at the most common causes of cancer death in both men (lung, prostate, and colorectal cancer), and women (lung, breast, and colorectal cancer). They found that prostate and breast cancer demonstrated the strongest associations with poor environmental quality. [Original study.]

The researchers point out that about half of cancers are thought to have a genetic component, but therefore the other half have environmental causes. Other studies already find that environmental exposures (e.g., pesticides, diesel exhaust) are linked to various cancers. But this study was an attempt to look at interactions of various things in the environment with rates of cancer - because we all are exposed to a number of things simultaneously wherever we live, not just to exposures to one thing. Thus this study looked at associations in rates of cancer. 

Of course there is also a lifestyle contribution to many cancers that wasn't looked at here (nutrition, alcohol use, exercise). They also pointed out that many counties in the US are large and encompass both very polluted and non-polluted areas - and that those counties should be broken up into smaller geographic areas when studied. [More air pollution studies.] From Science Daily:

Poor overall environmental quality linked to elevated cancer rates

Nationwide, counties with the poorest quality across five domains -- air, water, land, the built environment and sociodemographic -- had the highest incidence of cancer, according to a new study published in the journal Cancer. Poor air quality and factors of the built environment -- such as the presence of major highways and the availability of public transit and housing -- -- were the most strongly associated with high cancer rates, while water quality and land pollution had no measurable effect.

Previous research has shown that genetics can be blamed for only about half of all cancers, suggesting that exposure to environmental toxins or socioeconomic factors may also play a role. "Most research has focused on single environmental factors like air pollution or toxins in water," said Jyotsna Jagai, research assistant professor of environmental and occupational health in the University of Illinois at Chicago School of Public Health and lead author of the study. "But these single factors don't paint a comprehensive picture of what a person is exposed to in their environment -- and may not be as helpful in predicting cancer risk, which is impacted by multiple factors including the air you breathe, the water you drink, the neighborhood you live in, and your exposure to myriad toxins, chemicals and pollutants."

To investigate the effects of overall environmental quality, the researchers looked at hundreds of variables, including air and water pollution, pesticide and radon levels, neighborhood safety, access to health services and healthy food, presence of heavily-trafficked highways and roads, and sociodemographic factors, such as poverty. Jagai and her colleagues used the U.S. EPA's Environmental Quality Index, a county-level measure incorporating more than 200 of these environmental variables and obtained cancer incidence rates from the National Cancer Institute's Surveillance, Epidemiology, and End Results Program State Cancer Profiles. Cancer data were available for 85 percent of the 3,142 U.S. counties.

The average age-adjusted rate for all types of cancer was 451 cases per 100,000 people. Counties with poor environmental quality had higher incidence of cancer -- on average, 39 more cases per 100,000 people -- than counties with high environmental quality. Increased rates were seen for both males and females, and prostate and breast cancer demonstrated the strongest association with poor environmental quality.

The researchers found that high levels of air pollution, poor quality in the built environment and high levels of sociodemographic risk factors were most strongly associated with increased cancer rates in men and women. The strongest associations were seen in urban areas, especially for the air and built environment domains. Breast and prostate cancer were most strongly associated with poor air quality.

Published on Leave a comment on Does Vitamin D Prevent Cancer?

Does vitamin D prevent cancer? There has been much debate over whether increasing levels of vitamin D (as measured in a person's blood) results in a lower incidence of cancer. Studies find a number of health problems linked to low levels of vitamin D (here, here, here), while studies looking at vitamin D and cancer have been "inconsistent" in their results. Some say yes - vitamin D is protective, while some say there is no effect from vitamin D supplements. Now a 4 year study (yes, yes - it's a very short length of time in which to study the onset of cancer) found no difference in the rate of cancer among two groups of postmenopausal women who received either: 2,000 IU per day of vitamin D3 and 1,500 mg per day of calcium OR an identical looking placebo. They looked for any kind of cancer occurring.

The Creighton University researchers found a difference among the women after 4 years, with the vitamin D plus calcium supplement group having fewer cancers (and a lower percentage of cancer) as compared to the placebo group, but...it did not reach statistical significance. So you could say it was due to chance. But when the researchers looked at the number of cancers from year 2 to 4, then the difference was statistically significant - that vitamin D was protective. The researchers wonder if the cancers diagnosed in year 1 were already developing before the study started. Note: The 2,000 IU per day vitamin D3 supplements in this study are considered high doses - "high dose supplementation".

The researchers point out that the women who were given vitamin D3 and calcium supplements had a 30% lower risk of cancer, even though this difference in cancer incidence rates between the 2 groups did not quite reach statistical significance. But both groups started with a fairly high vitamin D level -  an average 25-hydroxyvitamin D (25[OH]D) levels of 32.8 ng/m (which is above the average US population level). And in the supplement group it was raised to 43.9 ng/mL. Note that some researchers view vitamin D levels of 33 ng/mL  (the baseline level in both groups) as already protective against cancer.

Also, even during the study the placebo group was allowed to take their own vitamin D and calcium supplements as long as it wasn't more than the recommended amounts (800 IU per day for vitamin D and 1500 mg per day for calcium) - which makes those individuals actually a low vitamin D supplementation group rather than no supplementation, which might hide any treatment effects and so make the results for the 2 groups look similar. What is needed is a much longer follow-up, larger groups of women, and both high and low dose vitamin D supplement groups. Some studies suggest that whether a low or high dose taken has an effect on cancer incidence.

I still think this study period was way too short - to me, 5 or more years would have been more convincing, and the groups too small. Also, it was unfortunate that they were also given calcium supplements or that there wasn't a just vitamin D group. Combining vitamin D with calcium supplements just muddies the results (in my opinion), and also because calcium supplements are linked to health problems such as cardiovascular disease. So in this study can't tell what the separate effects of calcium and vitamin D are. (Note that calcium rich foods, however, are beneficial to health.)

But a big positive of the study was that the women were randomly assigned to either the vitamin D plus calcium group or the placebo group, and no one - not the women or their doctors knew who got what until the end of the study (to eliminate bias it was "double-blind"). Note The supplements used were vitamin D3 and not D2. Vitamin D can also be easily obtained by exposure to sunlight in the summer months.

Excerpts from Creighton University release about the study in Science Daily: Does Vitamin D decrease risk of cancer?

The study, funded by the National Institutes of Health, is a randomized clinical trial of the effects of vitamin D supplementation on all types of cancer combined. The four-year study included 2,303 healthy postmenopausal women 55 years and older from 31 counties in Nebraska. Participants were randomly assigned to take either 2000 international units (IU) of vitamin D3 and 1500 mg. of calcium or identical placebos daily for 4 years. The vitamin D3 dose was about three times the US government's Recommended Dietary Allowance (RDA) of 600 IU for adults through age 70, and 800 IU for those 71 and older. Women who were given vitamin D3 and calcium supplements had 30% lower risk of cancer. This difference in cancer incidence rates between groups did not quite reach statistical significance. However, in further analyses, blood levels of vitamin D, specifically 25-hydroxyvitamin D (25(OH)D), were significantly lower in women who developed cancer during the study than in those who remained healthy.

Original study in JAMA: Effect of Vitamin D and Calcium Supplementation on Cancer Incidence in Older Women. Accompanying editorial about the study in JAMA:  Vitamin D, Calcium, and Cancer: Approaching Daylight?

Published on Leave a comment on Mediterranean Diet and Breast Cancer

Once again the Mediterranean diet is linked to health benefits - this time a 40% lower incidence of certain types of breast cancer in postmenopausal women. Following a Mediterranean style diet has been linked in earlier studies to various health benefits, such as lower rates of heart disease, lower rates of early death, and certain cancers.

A strength of this study is that so many (62,573) Dutch postmenopausal women were followed for a long time (about 20 years). Their diet was analyzed, especially how closely it matched the Mediterranean diet or not. Since alcohol is a risk factor for breast cancer, and dose-related - it was not included as part of the Mediterranean diet in this study. The study found that following a Mediterranean diet with higher consumption of nuts, fruits, vegetables, and whole grains, appeared to be protective against certain breast cancers - it was associated with a reduced risk of estrogen receptor–negative (ER-) breast cancers. Unfortunately the researchers did not look at olive oil use in this study, because when it started in 1986, it was not typically used in the Netherlands. However, another good study found extra virgin olive oil to be a protective part (against breast cancer) of the Mediterranean diet. From Medscape:

Mediterranean Diet Cuts Some Breast Cancer Risk by 40%

Closely following a Mediterranean diet in everyday life may significantly reduce the risk for types of breast cancer that are associated with poorer prognoses in postmenopausal women, new research indicates. The traditional Mediterranean diet is characterized by a high intake of plant proteins, whole grains, fish, and monounsaturated fat, as well as moderate alcohol intake and low intake of refined grains, red meat, and sweets, say the study authors, led by Piet A. van den Brandt, PhD, an epidemiologist at the Maastricht University Medical Center in the Netherlands.

The new findings come from 62,573 Dutch women aged 55 to 69 years who provided information on dietary and lifestyle habits in 1986 and have since been followed for more than 20 years....The investigators found that women who most closely adhered to a Mediterranean diet had a 40% reduced risk for estrogen receptor–negative (ER-) breast cancer compared to women who adhered to the diet the least. They found a 39% reduced risk for progesterone receptor–negative (PR-)/ER- disease when comparing these same high- and low-adherence groups. Notably, in these results, the definition of the diet excluded alcohol intake, because the consumption of alcohol is a known risk factor for breast cancer....The authors also report that there were no significant associations with the diet and the risk of ER+ disease or total breast cancer.

Dr van den Brandt also explained that older women, who were the subjects of the new study, are more likely to derive benefit than younger women. "Generally speaking, postmenopausal breast cancer seems somewhat more influenced by environmental factors, such as lifestyle and diet, than premenopausal breast cancer, where genetic factors seem to play a more prominent role," he told Medscape Medical News.

Dr Toledo was the senior author of the only large, randomized trial to date in which postmenopausal women were assigned to a dietary intervention to promote their adherence to the traditional Mediterranean diet (JAMA Intern Med. 2015;175:1752–60). The study found that women with a higher adherence to the diet (supplemented with extra-virgin olive oil) showed a substantial reduction of their risk for breast cancer compared to a control group, as reported by Medscape Medical News.