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The last post was about several reviews of vitamin D studies, and how when people are put randomly into different groups and then followed for a while - that the studies generally are not finding the same wonderful effects of higher levels of vitamin D in the blood that observational studies are finding - instead finding no effect or mixed results. Some issues with observational studies: the groups are self-selected, some are a one time snapshot of a person (thus one can't tell what happens over time); and can't prove cause and effect (can only say there is an association or link). [See all posts about vitamin D.]

But anyway, today's post is about some more vitamin D studies, all published in 2018. All of them find health benefits from higher blood levels of vitamin D. What is an ideal level of vitamin D varies from study to study, and some are observational - thus can only say "find an association with" in the findings. The fifth study finds beneficial effects from higher doses of vitamin D, and the participants were randomly assigned to the groups (good!). Click on links to read details. All excerpts are from Science Daily:

Vitamin D deficiency linked to greater risk of diabetes

An epidemiological study conducted by researchers at University of California San Diego School of Medicine and Seoul National University suggests that persons deficient in vitamin D may be at much greater risk of developing diabetes. The findings are reported in the April 19, 2018 online issue of PLOS One ...continue reading "Five Studies Looking at Vitamin D and Health"

Does the type of iron in supplements and additives matter for your health? OK, this was a preliminary study and done in a lab using human cells, which means much more research needs to be done, but... It may be that different forms of iron in supplements and additives have slightly different effects in the human body, specifically the intestines. Ferrous sulphate so far looks good (had no effect on the cancer cells studied), while 2 other forms of iron - ferric citrate and ferric EDTA - may actually promote the formation of colon cancer. That is, they may be considered carcinogenic.

Ferric EDTA and ferric citrate have been observed to promote colon cancer in studies using mice. Bottom line: When buying supplements and foods, check labels to make sure the iron is in the form of ferrous sulphate, and not ferric citrate or ferric EDTA. From Science Daily:

Certain iron supplements may influence the development of colon cancer ...continue reading "Perhaps The Type Of Iron Supplement Matters"

A recent study published in BMJ (British Medical Journal) found a link between high consumption of ultra-processed food and higher rates overall of cancer, but also a higher risk of breast cancer. Specifically, a 10% increase in the proportion of ultra-processed foods in the diet was associated with a greater than 10% increase of overall cancer and 11% increase of breast cancer during the 6+ years of the study.

Alarmingly (because of the health implications), several surveys (in Europe, the US, Canada, New Zealand, and Brazil) have suggested that ultra-processed food products are now between 25 to 50% of calories eaten every day.

Ultra-processed food is food that is highly processed. It is food that is mass produced and packaged, as well as foods that have manufactured substances in them - such as hydrogenated oils (also contains trans fats), protein isolates, additives, preservatives, artificial or natural flavors, colors, nitrites (in processed meat), titanium dioxide (nanoparticles), etc. The food packaging can leach chemicals such as pthalates (endocrine disruptors). The list goes on and on and on. All of these things in ultra-processed foods may be involved in causing health problems, including cancer. They are typically also poorer nutritionally and higher in salt than unprocessed or minimally processed foods. These ultra-processed foods that are so popular are all around us - in fast food, in mass produced desserts and breads, packaged snacks, soups, cold cuts, margarine, frozen or shelf stable ready to eat meals, instant foods, sodas and drinks, etc.

On the other hand, unprocessed or minimally processed foods are fresh, dried, ground, chilled, frozen, pasteurised, or fermented foods such as fruits, vegetables, legumes (beans), rice, pasta, eggs, meat, fish, or milk. There are also “processed culinary ingredients”  which are salt, vegetable oils, butter, sugar, and other substances extracted from foods and used in kitchens to transform unprocessed or minimally processed foods into "culinary preparations" (meals). The study did NOT find any association with unprocessed, minimally processed, or processed culinary ingredients with cancer. Only with the ultra-processed food. Instead, the study found that higher consumption of “minimally/unprocessed foods” (and lower ultra-processed food) was associated with lower risks of overall cancer and breast cancer.

So an apple is unprocessed, and plain apple sauce made with just apples is minimally processed, while a packaged apple dessert with additives added is ultra-processed. Think of it as "transformed food". Also keep in mind that your beneficial gut microbes like unprocessed or minimally processed food - especially those high in fiber. You know - a diet rich in fruits, vegetables, whole grains, seeds, nuts, legumes (beans).  ...continue reading "Ultra-Processed Food and Risk of Cancer"

The results of a recent study in the United Kingdom are in line with what a number of researchers (here, here, and here) have been writing about for a while - that studies show that some cancer screening (e.g. for prostate cancer) of people with no symptoms does not save lives.

The UK study randomly assigned men (aged 50 to 69) to get a PSA test one time or to not get a PSA test (the controls). The PSA test measures prostate-specific antigen in the blood, and is typically used to screen for prostate cancer. It is not done routinely in the UK. They found that while more men were diagnosed with prostate cancer in the PSA group, after 10 years there was no statistical difference in death rates between the two groups. As the researchers themselves said, the PSA screening test resulted in "an increase in the detection of low-risk prostate cancer cases" (the ones that wouldn't cause a problem). But not in the aggressive killer cancers.  However, the researchers are now continuing the study to see if there are differences in the 2 groups after an even longer period of time. From Medical Xpress:

One-off PSA screening for prostate cancer does not save lives

Inviting men with no symptoms to a one-off PSA test for prostate cancer does not save lives according to results from the largest ever prostate cancer trial conducted over 10 years by Cancer Research UK-funded scientists and published today (Tuesday) in the Journal of the American Medical Association (JAMA). Researchers at the Universities of Bristol and Oxford found that testing asymptomatic men with PSA detects some disease that would be unlikely to cause any harm but also misses some aggressive and lethal prostate cancers.

The CAP Trial, which spanned almost 600 GP practices in the UK and included more than 400,000 men aged 50-69, is the largest trial ever to investigate prostate cancer screening. The trial compared 189,386 men who were invited to have a one-off PSA test with 219,439 men who were not invited for screening. After an average of 10 years follow up, there were 8,054 (4.3%) prostate cancers in the screened group and 7,853 (3.6%) cases in the control group. Crucially, both groups had the same percentage of men dying from prostate cancer (0.29%).

While some prostate cancers are aggressive and lethal, others are clinically insignificant and will never lead to any harm or death if left undetected. Ideally, aggressive prostate cancers need to be identified and treated as early as possible. But finding a cancer that would never have caused men harm during their lifetime can have a serious impact on quality of life, including the worry of a cancer diagnosis, the possibility of infection following a biopsy and impotence and incontinence following treatment. ... Dr Richard Roope, Cancer Research UK's GP expert, said: "The PSA test is a blunt tool missing the subtleties of the disease and causing men harm.

Are there foods that could prevent cancer? Well... studies show that a dietary pattern with lots of fiber, and perhaps along the lines of the Mediterranean diet, may be the most beneficial. In other words, it's not just one or a few "super-foods" that a person should eat, but an overall dietary pattern. But one specific food does appear beneficial for health - nuts, specifically tree nuts.

Researchers at the Yale Cancer Center followed a large group of stage 3 colon cancer patients after they had been treated for about 6.5 years, and looked at how frequently they consumed nuts. (Stage 3 colon cancer means it had spread to lymph nodes, but not to distant sites like the liver and lungs.) They found an association with frequent consumption (2 or more servings per week) of tree nuts (walnuts, hazelnuts, almonds, cashews, pecans, etc.) and a 42% lower incidence of the colon cancer recurring and 57% lower death rate. However, these findings did not apply to peanuts, which are legumes. [NOTE: One ounce or a handful of nuts is considered a serving.]

Why would nuts be beneficial? Generally speaking, nuts lower inflammation and insulin resistance. The lead researcher Dr. Charles Fuchs said that "behaviors that make you less insulin-resistant, including eating nuts, seem to improve outcomes in colon cancer". Parts of this research were discussed last year, but now it has been written up in the Journal of Clinical Oncology. ...continue reading "Nuts And Colon Cancer"

Once again, a study found an association between a worrisome health problem (intestinal polyps) with a dietary supplement (calcium), but no problems with eating the foods (calcium rich foods). The large multi-center study specifically looked at serrated polyps (SPs) because they are considered precursor lesions for colorectal cancer - that is, that while they are not cancerous, some of them will develop into cancer. Persons invited to join the study had a recent colonoscopy with at least one adenomatous polyp detected and removed, and then were scheduled for another colonoscopy 3 to 5 years later. This was considered a "chemoprevention study" to see if certain supplements help prevent polyps (and thus cancer).

People in different parts of the US were randomly assigned to either receive calcium supplements (1200 mg/day of elemental calcium), vitamin D (1000 IU/day of vitamin D3),  both supplements (calcium supplement plus vitamin D), or neither. Supplement treatment continued for 3 to 5 years and then there was an observational period that was 6 to 10 years after the person first started supplementation. The higher incidence of serrated polyps was a "late effect" (6 to 10 years later) and not seen during the treatment time (the first 3 to 5 years). They found that women and current smokers had higher risks of serrated polyps when exposed to supplemental calcium. Vitamin D alone was not linked with polyps.

Other studies have also found an association between calcium supplements and increased risk of certain health problems, and a lower incidence of polyps with a higher intake of dietary calcium (real food). The researchers said: "Patients with a history of premalignant serrated polyps, especially women and smokers, may wish to avoid vitamin D and calcium supplementation." BOTTOM LINE: General guidelines should be to eat foods, not supplements, to get your nutrients, vitamins, and minerals. There are many studies also at this point that a high fiber diet with lots of fruits, vegetables, whole grains, legumes (beans), nuts, seeds are associated with better intestinal health and fewer polyps (here, here). Another way to view it is: feed your beneficial gut microbes with good, real food. And especially not highly processed junk. From Medical Xpress:

Calcium supplements may boost risk of abnormal bowel growths

Calcium supplements, taken with or without vitamin D, may increase the risk of small growths in the large bowel (colon) called polyps, suggest results from a large US trial published online in the journal Gut. Polyps are small growths in the lower part of the large bowel. They are non-cancerous, but some could eventually turn into cancer if they are not removed. Polyps come in different shapes and sizes, and this study specifically focused on the risk of serrated polyps, which are less common than conventional "adenomatous" polyps, but likely have the same risk of developing into cancer. 

...continue reading "Best to Eat Calcium Rich Foods, Not Calcium Supplements"

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.

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 harmlesscauses 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.”

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.

A new observational study from Taiwan found that having one of eight chronic diseases, such as heart disease or diabetes, or their markers (e.g. high cholesterol levels as a marker for heart disease), also significantly raises the person's odds of developing cancer or dying from cancer. The study estimated that these diseases or markers accounted for about 20% of all new cancers and 39% of all cancer deaths. That's about the risk of 5 lifestyle factors combined (smoking, alcohol consumption, obesity, unhealthy diet, and lack of exercise) contributing to cancer development and death.

The eight chronic diseases and markers were: cardiovascular disease (markers for which include blood pressure, total cholesterol, and heart rate), diabetes, chronic kidney disease (markers for which include proteinuria and glomerular filtration rate), pulmonary disease, and gouty arthritis (for which uric acid is a marker). The higher the chronic disease and marker score, the higher the risk of developing cancer and cancer death (a dose-response). Chronic diseases and markers were associated with a shortened lifespan -  about 13.3 years in men and 15.9 years in women.

But the good news is that regular physical exercise lowers the risk of developing cancer by about 48% and the risk of cancer death by 27%. That's huge!  So physical exercise and activity could be viewed as "cancer prevention" strategies. The researchers pointed out that additional cancer prevention strategies are avoiding smoking (very important), avoiding excessive alcohol consumption, maintaining healthy weight, and a healthy diet. From Science Daily:

Substantial impact of chronic diseases on cancer risk

Several common chronic diseases together account for more than a fifth of new cancer cases and more than a third of cancer deaths, finds a study published by The BMJ today. The findings show that the cancer risks from common chronic diseases, such as heart disease and diabetes, are as important as those from five major lifestyle factors combined.

A team of researchers based in the US and Taiwan therefore set out to investigate the combined effect of eight common chronic diseases or disease markers (for example, high blood pressure as a marker of heart disease) on cancer risk compared with lifestyle factorsThey also explored whether physical activity could reduce the cancer risk associated with chronic diseases and disease markers. The study involved 405,878 men and women in Taiwan with no history of cancer .... underwent a series of medical tests between 1996 and 2007. .... Participants were followed for an average of 8.7 years.

The researchers found that cardiovascular disease markers, diabetes, chronic kidney disease markers, pulmonary disease, and gouty arthritis marker were individually associated with risk of developing cancer or cancer death. Higher chronic disease risk scores based on these diseases or markers were linked with an increased risk of developing cancer and cancer death, with the highest level associated with a more than twofold increase in risk of developing cancer and a fourfold increase in risk of cancer death.

High chronic disease risk scores were also associated with substantial reduction in life span. The highest scores were associated with 13.3 years of life lost in men and 15.9 years of life lost in women. Together, these chronic diseases and markers accounted for more than one fifth of all new cancers and more than one third of all cancer deaths in this study population, which was similar to the contribution of five major lifestyle risk factors combined -- smoking, insufficient physical activity, insufficient fruit and vegetable intake, alcohol consumption, and obesity.

The researchers also found that physical activity was associated with a nearly 40% reduction in the excess risks of cancer and cancer death associated with chronic diseases and markers. [Original study.]

There have been many posts on this blog about diet, fiber, microbes, and the association of diet with various diseases, such as cancer. A recent journal article by M. Song and A. Chan reviewed studies that looked at the link between diet, gut microbes (the gut microbiota or gut microbiome), and colorectal cancer (what we typically call colon cancer).

In summary, research from the last 20 years has found that diet and colorectal cancer (CRC) go hand in hand, and that diet determines the microbes (microbiota) living in the gut - that is, what you feed the microbes determines what microbes will live and thrive in the gut. Also, certain microbes in the gut are linked to inflammation and cancer formation, and others to its prevention. In other words, there is potential to prevent colorectal cancer with certain diets, and to increase the odds of colorectal cancer with other diets.

What are main dietary factors linked to colorectal cancer? Western diet (lots of processed foods, red and processed meat, low in fiber, refined grains), low levels of dietary fiber, low intake of omega-3 fatty acids from seafood (or fish oil), and obesity. The researchers point out that a Western diet is associated with gut dysbiosis (microbial imbalance), loss of gut barrier integrity, and increased levels of inflammation. What should one do? Basically think to yourself: "I need to feed the beneficial microbes in my gut, so I need to eat lots of fruits, vegetables, whole grains, and seafood (omega-3 fatty acids)" - this is what the researchers call a "prudent pattern diet". And try to maintain a normal weight. Some excerpts from Current Colorectal Cancer Reports:

Diet, Gut Microbiota, and Colorectal Cancer Prevention: a Review of Potential Mechanisms and Promising Targets for Future Research

AbstractDiet plays an important role in the development of colorectal cancer. Emerging data have implicated the gut microbiota in colorectal cancer. Diet is a major determinant for the gut microbial structure and function. Therefore, it has been hypothesized that alterations in gut microbes and their metabolites may contribute to the influence of diet on the development of colorectal cancer.We review several major dietary factors that have been linked to gut microbiota and colorectal cancer, including major dietary patterns, fiber, red meat and sulfur, and obesity

Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the fourth leading cause of cancer death in the world. Over the past few decades, numerous epidemiologic studies have identified a range of dietary factors that may potentially promote or prevent CRC. Likewise, increasing evidence has implicated the gut microbiota in CRC development. Biological plausibility is supported by habitation of numerous gut microbes in the large intestine and the functional importance of the gut microbiota in maintenance of the gut barrier integrity and immune homeostasis, the disruptions of which are among the most important mechanisms in colorectal carcinogenesis. Given the critical role of diet in the configurations of gut microbial communities and production of bacterial metabolites, it has been proposed that diet may influence CRC risk through modulation of the gut microbial composition and metabolism that in turn shape the immune response during tumor development.

Although gut bacterial abundance may respond rapidly to extreme changes in diet, predominant microbial community membership is primarily determined by long-term diet, and substantial inter-individual variation persists despite short-term dietary change. .... Thus, this review focuses on the dietary factors that have strong mechanistic support, including dietary pattern, fiber, red meat and sulfur, and omega-3 fatty acid. Given the close link between diet and obesity and the predominant role of obesity in CRC as well as the substantial data linking the gut microbiome to obesity, we also include obesity at the end of the review.

DIETARY PATTERNS: Convincing data indicate that a “Western dietary pattern,” characterized by high intake of red or processed meat, sweets, and refined grains, is associated with higher risk of colorectal neoplasia; in contrast, diets that are rich in fruits, vegetables, and whole grains (“prudent pattern diet”) are associated with lower risk of CRC. Western diets are associated with gut dysbiosis (microbial imbalance), loss of gut barrier integrity, increased levels of inflammatory proteins, and dysregulated immune signatures.

A potential role of the gut microbiota in mediating the dietary associations with CRC risk is suggested by the dramatic difference of the gut microbial structures between populations consuming different diets. Rural Africans, whose diet is high in fiber and low in fat, have a strikingly different gut microbial composition than urban Europeans or African Americans consuming a Western diet, which parallels the lower CRC rates in Africa than Western countries. For example, the African gut microbiota is characterized by a predominance of Prevotella genus that are involved in starch, hemicellulose, and xylan degradation, whereas the American microbiota is predominated by Bacteroides genus with a higher abundance of potentially pathogenic proteobacteria, such as Escherichia and Acinetobacter. .... Moreover, a crossover study indicates that switching African Americans to a high-fiber, low-fat diet for 2 weeks increases production of SCFAs, suppresses secondary bile acid synthesis, and reduces colonic mucosal inflammation and proliferation biomarkers of cancer risk.

Fiber: Numerous prospective studies have linked higher fiber intake to lower risk of CRC. The most recent expert report from the World Cancer Research Fund and the American Institute for Cancer Research in 2011 concludes that evidence that consumption of foods containing dietary fiber protects against CRC is convincing. Besides systemic benefits for insulin sensitivity and metabolic regulation, which have been implicated in colorectal carcinogenesis, fiber possesses gut-specific activities, such as diluting fecal content, decreasing transit time, and increasing stool weight, thereby minimizing exposure to intestinal carcinogens.

Moreover, soluble fiber can be fermented by bacteria in the lumen of the colon into SCFAs [short-chain fatty acids], including butyrate, acetate,and propionate. Higher fiber intake has been shown to enrich butyrate-producing bacteria in the gut, such as Clostridium, Anaerostipes, Eubacterium, and Roseburia species, and increase production of SCFAs. SCFAs have been suggested as the key metabolites linking the gut microbes to various health conditions, especially CRC

Red Meat and Sulfur: There is convincing evidence that red and processed meats are associated with increased risk of CRC. Recently, the Int. Agency for Research on Cancer has classified processed meat as a carcinogen to humans. Mechanisms underlying the pro-cancer effects of red or processed meats include heme iron, N-nitroso compounds, or heterocyclic amines, and hydrogen sulfide production. Hydrogen sulfide has been implicated in inflammatory disorders associated with risk of CRC, such as ulcerative colitis, and directly with CRC.

Omega-3 Fatty Acid: Marine omega-3 polyunsaturated fatty acid, including eicosapentaenoic acid, docosahexaenoic acid, and docosapentaenoic acid, possesses potent anti-inflammatory activity and may protect against CRC. Fish oil, a rich source of omega-3 fatty acid, is the most popular natural product used by US adults. Substantial data support the beneficial effect of omega-3 fatty acid on CRC prevention and treatment.

Dietary fat composition is a major driver of the gut microbial community structure. Compared to other types of fat, omega-3 fatty acid have been associated with higher intestinal microbiota diversity and omega-3 fatty acid-rich diet ameliorates the gut dysbiosis induced by omega-6 polyunsaturated fatty acid or antibiotics.

Obesity: Since the 1970–1980s, the prevalence of obesity has markedly increased worldwide. The obesity epidemic is believed to be largely driven by global westernization characterized by overconsumption of easily accessible and energy-dense food and a sedentary lifestyle. Obesity is an established risk factor for CRC and several other cancers. Possible mechanisms include increased insulin levels and bioavailability of insulin-like growth factor 1, altered secretion of adipokines and inflammatory cytokines, and changes in sex hormone levels.