Resveratrol And VDR

Resveratrol is purported to have a number of health benefits; this paper explains one possible mechanism of action, abstract:

The 1,25-dihydroxyvitamin D3 (1,25D) hormone is derived from vitamin D generated in skin or obtained from the diet, and binds to and activates the vitamin D receptor (VDR) in target tissues including kidney, colon/small intestine, and bone/muscle. We tested resveratrol for its ability to modulate VDR signaling, using vitamin D responsive element (VDRE) and mammalian 2-hybrid (M2H) transcriptional system technology. Via VDRE-based assays in kidney, colon and myoblast cells, VDR-mediated transcription was activated by resveratrol, and a cooperative effect on transactivation was observed with resveratrol plus 1,25D. The M2H assay revealed a modest, resveratrol-induced dimerization of VDR with its retinoid X receptor (RXR) heteropartner. Cells treated with both resveratrol and 1,25D displayed synergistic stimulation of VDR-RXR heterodimerization, while resveratrol antagonized rexinoid-mediated RXR-RXR homodimerization. Increased transactivation in response to resveratrol was also observed with a subset of other nuclear receptors and their respective cognate responsive elements. Evaluation of wild-type versus a ligand-binding domain mutant VDR revealed that hormone-responsiveness to 1,25D was severely depressed, while the response to resveratrol was only moderately attenuated. Moreover, radiolabeled 1,25D-displacement assays demonstrated an increase in VDR-bound 1,25D in the presence of resveratrol. Thus, resveratrol may affect VDR and other nuclear receptors indirectly, likely via the ability of resveratrol to: (1) potentiate 1,25D binding to VDR; (2) activate RXR; and/or (3) stimulate SIRT1, an enzyme known to deacetylate nuclear receptors. The results of this study elucidate a possible pathway for crosstalk between two nutritionally derived lipids, vitamin D and resveratrol, both of which converge on VDR signaling.

Vitamin D and vitamin D signaling continuously proves to be extremely important for human health and disease prevention.

Cancer Incidence In Different Parts Of The USA

Different forms of cancer seem more prevalent in some areas of the USA compared to others.  For example, read here. Part of abstract:

For many cancers, there were distinct clusters of counties with especially high mortality. The location of these clusters varied by type of cancer and were spread in different regions of the United States. Clusters of breast cancer were present in the southern belt and along the Mississippi River, while liver cancer was high along the Texas-Mexico border, and clusters of kidney cancer were observed in North and South Dakota and counties in West Virginia, Ohio, Indiana, Louisiana, Oklahoma, Texas, Alaska, and Illinois.
CONCLUSIONS AND RELEVANCE:
Cancer mortality declined overall in the United States between 1980 and 2014. Over this same period, there were important changes in trends, patterns, and differences in cancer mortality among US counties. These patterns may inform further research into improving prevention and treatment.

This differences can be due to genetic differences between demographic groups variably distributed in these regions, differences in lifestyle including diet and physical activity, different distribution of age groups in these regions, socioeconomic status and access to health care, etc.  As the authors state, hopefully this information can be useful in optimizing prevention and treatment.

Fiber And Microbiota

Dietary fiber can increase levels of certain gut microbiota bacterial species, as well as higher levels of butyrate, a short chain fatty acid with beneficial anti-cancer effects in the colon.  Abstract:

BACKGROUND:

Dysfunction of the gut microbiota is frequently reported as a manifestation of chronic diseases, and therefore presents as a modifiable risk factor in their development. Diet is a major regulator of the gut microbiota and certain types of dietary fiber may modify bacterial numbers and metabolism, including short-chain fatty acid (SCFA) generation.

OBJECTIVE:

A systematic review and meta-analysis were undertaken to assess the effect of dietary fiber interventions on gut microbiota composition in healthy adults.

DESIGN:

A systematic search was conducted across MEDLINE, EMBASE, CENTRAL, and CINAHL for randomized controlled trials using culture and/or molecular microbiological techniques evaluating the effect of fiber intervention on gut microbiota composition in healthy adults. Meta-analyses via a random-effects model were performed on alpha diversity, prespecified bacterial abundances including Bifidobacterium and Lactobacillus spp., and fecal SCFA concentrations comparing dietary fiber interventions with placebo/low-fiber comparators.

RESULTS:

A total of 64 studies involving 2099 participants were included. Dietary fiber intervention resulted in higher abundance of Bifidobacterium spp. [standardized mean difference (SMD) 0.64 (95% CI: 0.42, 0.86); P < 0.00001)] and Lactobacillus spp. [SMD: 0.22 (0.03, 0.41), P = 0.02] as well as fecal butyrate concentration [SMD: 0.24 (0.00, 0.47), P = 0.05] compared with placebo/low-fiber comparators. Subgroup analysis revealed that fructans and galacto-oligosaccharides led to significantly greater abundance of both Bifidobacterium spp. and Lactobacillus spp. compared with comparators (P < 0.00001 and P = 0.002, respectively). No differences in effect were found between fiber intervention and comparators for α-diversity, abundances of other prespecified bacteria, or other SCFA concentrations.

CONCLUSIONS:

Dietary fiber intervention, particularly involving fructans and galacto-oligosaccharides, leads to higher fecal abundance of Bifidobacterium and Lactobacillus spp. but does not affect α-diversity. Further research is required to better understand the role of individual fiber types on the growth of microbes and the overall gut microbial community. This review was registered at PROSPERO as CRD42016053101.

Dietary Influences On The Plasma Membrane: Cancer Implications

Diet can affect the cell plasma membrane and hence decrease caner risk, through modulation of cell signaling. Abstract:

The cell plasma membrane serves as a nexus integrating extra- and intracellular components, which together enable many of the fundamental cellular signaling processes that sustain life. In order to perform this key function, plasma membrane components assemble into well-defined domains exhibiting distinct biochemical and biophysical properties that modulate various signaling events. Dysregulation of these highly dynamic membrane domains can promote oncogenic signaling. Recently, it has been demonstrated that select membrane-targeted dietary bioactives (MTDBs) have the ability to remodel plasma membrane domains and subsequently reduce cancer risk. In this review, we focus on the importance of plasma membrane domain structural and signaling functionalities as well as how loss of membrane homeostasis can drive aberrant signaling. Additionally, we discuss the intricacies associated with the investigation of these membrane domain features and their associations with cancer biology. Lastly, we describe the current literature focusing on MTDBs, including mechanisms of chemoprevention and therapeutics in order to establish a functional link between these membrane-altering biomolecules, tuning of plasma membrane hierarchal organization, and their implications in cancer prevention.

More On Gut Microbiota And Colorectal Cancer

Another paper about gut microbiota and colorectal cancer is of interest.  Abstract:

Pre-clinical and clinical data produce mounting evidence that the microbiota is strongly associated with colorectal carcinogenesis. Dysbiosis may change the course of carcinogenesis as microbial actions seem to impact genetic and epigenetic alterations leading to dysplasia, clonal expansion and malignant transformation. Initiation and promotion of colorectal cancer may result from direct bacterial actions, bacterial metabolites and inflammatory pathways. Newer aspects of microbiota and colorectal cancer include quorum sensing, biofilm formation, sidedness and effects/countereffects of microbiota and probiotics on chemotherapy. In the future, targeting the microbiota will probably be a powerful weapon in the battle against CRC as gut microbiology, genomics and metabolomics promise to uncover important linkages between microbiota and intestinal health.

Again we see the paradigm that targeting the gut microbiota, to yield a more healthy bacterial profile,c can be a future anti-cancer approach.

More On Cancer Prevention And Lifestyle

Here is recent news on yet another study linking lifestyle to cancer risk.  These are all things you, as a reader of this blog, should be well aware of by now.  The importance of curbing these behaviors to reduce cancer risk is underscored by these additional data.

Researchers with the American Cancer Society looked at data on cancer incidence and deaths, finding that 42 percent of all cancer cases in the United States -– and nearly half of all cancer deaths – are linked to preventable risk factors like cigarette smoking, exposure to secondhand smoke, excess body weight, alcohol intake and dietary choices.

Cigarette smoking, in particular, was connected to far more cancer cases and deaths than any other single risk factor, accounting for 19 percent of all cancer cases and 28.8 percent of deaths. Overweight and obesity came in second, responsible for 7.8 percent of cases and 6.5 percent of deaths, while alcohol intake was the third most important factor, leading to 5.6 percent of cancer cases and 4 percent of deaths.

Although there are some sex-specific differences as to the relative importance of various risk factors, the bottom line is that these things – smoking/overweight/obese, bad diets, certain STDs, alcohol – are bad for everyone.  Be aware and adjust your life accordingly, to the extent you are able.

Yet More On The Microbiota Colon Cancer Connection

A review paper asserts, from the abstract:

From the abstract:

Colorectal cancer (CRC) is the third most common cancer and the fourth most common cause of cancer-related death. Most cases of CRC are detected in Western countries, with its incidence increasing year by year. The probability of suffering from colorectal cancer is about 4%-5% and the risk for developing CRC is associated with personal features or habits such as age, chronic disease history and lifestyle. In this context, the gut microbiota has a relevant role, and dysbiosis situations can induce colonic carcinogenesis through a chronic inflammation mechanism. Some of the bacteria responsible for this multiphase process include Fusobacterium spp, Bacteroides fragilis and enteropathogenic Escherichia coli.

It is becoming increasingly clear that modification of gut microbiota, possibly through diet and/or probiotics, will become an important tool in the prevention and treatment of many diseases, including CRC.

Diet And Colorectal Cancer: Nucleus To Cell Membrane

Review article:

The International Agency for Research on Cancer recently released an assessment classifying red and processed meat as "carcinogenic to humans" on the basis of the positive association between increased consumption and risk for colorectal cancer. Diet, however, can also decrease the risk for colorectal cancer and be used as a chemopreventive strategy. Bioactive dietary molecules, such as n-3 polyunsaturated fatty acids, curcumin, and fermentable fiber, have been proposed to exert chemoprotective effects, and their molecular mechanisms have been the focus of research in the dietary/chemoprevention field. Using these bioactives as examples, this review surveys the proposed mechanisms by which they exert their effects, from the nucleus to the cellular membrane. In addition, we discuss emerging technologies involving the culturing of colonic organoids to study the physiological effects of dietary bioactives. Finally, we address future challenges to the field regarding the identification of additional molecular mechanisms and other bioactive dietary molecules that can be utilized in our fight to reduce the incidence of colorectal cancer.

Certain bioactive dietary factors have a protective effect against colorectal cancer, and scientists are investigating the cellular mechanisms behind these effects.

Eat your fiber!

Eat, drink, smoke – no problem

In March this year, there was yet another feast of ignorance, but I could not bring myself to address it until now.

It was reported at that time that “about two-thirds of cancers are caused by random typos in DNA that occur as normal cells make copies of themselves”. 

The report was based upon a "reiterated" research paper by B. Vogelstein.and his mathematician C. Tomasetti. The “finding” supposedly explained why healthy people still get cancer. In other words, no matter how diligently you take care of yourself and how healthy your lifestyle is, you can still develop cancer. 

This part is TRUE. All of us have cells that divide (i.e., replicate), and mistakes are introduced in cells’ DNA during replication. These mistakes may turn out to be mutations that can drive cancer development.

However, the esteemed researchers did not elaborate on the other side of the story: if you do not put any effort into being and staying healthy, if you are obese, physically inactive, smoke and drink, then you do have a HIGHER chance of developing cancer.

The two researchers estimated that 66 percent of mutations in cancers resulted from copying errors (during replication), the rest were due to lifestyle, environmental factors, and inheritance.

What the researchers COULD NOT AND DID NOT estimate was how many replication-introduced DNA errors were eliminated in some people, and therefore, these people NEVER developed cancer. Remember, individuals who lead a healthy lifestyle have also a healthy immune system that eliminates many of the cells with mutations (i.e., DNA errors). Many mutations are also “intercepted” by additional control mechanisms, and the cells can either repair the mistakes in the DNA or kill themselves (i.e., the cells commit to apoptosis).
 
Therefore, a better question that the researchers could have pondered was, why the DNA mistakes are sometimes not “addressed” by the control mechanisms. The esteemed researchers did not discuss that some DNA mistakes are not corrected/addressed by the natural control surveillance mechanisms simply because people have unhealthy lifestyle: eat too much sugar, become overweight/obese, stress out, do not move too much, drink and smoke, etc.

But then isn’t it more interesting to say one side of the story and fatalistically conclude that “most cancers are due to bad luck”?  After all, the words "bad luck" make a much more interesting title.

By the way, the fact that our DNA replication machinery is not perfect has been known for a long time. There is a silver lining to this imperfection – if there were no changes introduced in the DNA, we would not have had evolved from apes to whatever we think we are today.

Here are some comments that appeared after the quoted above article:

“…well that makes us all feel better now we know that its just bad luck”

“…Sounds like the "cancer prevention" industry - which is massive is busy spinning the truth!”

“…Genetics are the key factor. It basically refutes the diet fanatics, and their bleeting about health benefits of certain diets.”
 
The  comments are a prime example of how general public education marches on!

Breast cancer risk

Decrease your risk of breast cancer by more than 30%. 

AICR tells you how.

Just do not follow the AICR recipes!

More On Diet, Gut Microbiota, And Colorectal Cancer

At left, colorectal cancer diagram, By Blausen Medical Communications, Inc. - Donated via OTRS, see ticket for details, CC BY 3.0, https://commons.wikimedia.org/w/index.php?curid=27639260

Certain bacterial species in the gut microbiota enhanced risk of colorectal cancer (CRC).  Can diet influence the risk of developing CRC associated with those bacteria?  The answer seems to be yes, as described in this paper.  Excerpts from the abstract:

Importance: Fusobacterium nucleatum appears to play a role in colorectal carcinogenesis through suppression of the hosts' immune response to tumor. Evidence also suggests that diet influences intestinal F nucleatum. However, the role of F nucleatum in mediating the relationship between diet and the risk of colorectal cancer is unknown.

Objective: To test the hypothesis that the associations of prudent diets (rich in whole grains and dietary fiber) and Western diets (rich in red and processed meat, refined grains, and desserts) with colorectal cancer risk may differ according to the presence of F nucleatum in tumor tissue.

Conclusions and Relevance: Prudent diets rich in whole grains and dietary fiber are associated with a lower risk for F nucleatum - positive colorectal cancer but not F nucleatum - negative cancer, supporting a potential role for intestinal microbiota in mediating the association between diet and colorectal neoplasms.

In summary, diets high in whole grains and fiber reduce risk of CRC associated with F nucleatum, but not for CRC not associated with that species. This is evidence that the gut microbiota plays an important role in mediating the effects of diet on CRC, and further suggests the power of diet and gut microbiota management for cancer prevention.  I’ll be eating my whole grains and fiber.

Adenoma Detection Rates In Obese And Smoking Patients

At left, stained adenoma under the microscope.

By Nephron - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=8273894

Here is a study showing higher detection rates for adenomas and serrated adenomas in obese and smoking patients undergoing colonoscopy. Adenomas are benign tumors that - if left in the colon - have a probability of turning into full-fledged cancer (e.g., for a given polyp, could be a 10% chance in 10 years). Therefore, when detected in endoscopic screening, adenomas are typically removed.  The more adenomas, the greater the chance for cancer, so it is not surprising that obese and smoking individuals tend to have higher rates of colorectal cancer, since they are developing more of the pre-cancerous adenomas.

This again underscores the fundamental importance of maintaining a healthy bodyweight and to refrain from smoking.  If you are already at a normal weight and do not smoke, great, keep it up; if not, lose weight and make every attempt to quit smoking.  In general people associate obesity with diabetes and smoking with lung cancer, and those associations are indeed correct; however, there are many, many diseases associated with both obesity and smoking - including colorectal cancer - so the health ramifications of weight control and no smoking are enormous.

Colonary Concepts Update

I previously wrote about the company Colonary Concepts and their development of a more palatable colonoscopy prep, something which from personal experience I can say is sorely needed. I found some updated information from their website that I reproduce below. The good news: they’ve gotten to the stage of a Phase 3 clinical trial, and their product may be ready for launch by early 2019. That would be a welcome (and long overdue!) development.

Where are you in the development process?

Our colon prep candidate is currently entering our Phase 3 clinical trial, following a successful Phase 1 at the Dartmouth-Hitchcock Medical Center, and a successful Phase 2 at the Indiana University Health and Dartmouth-Hitchcock Medical Centers.

Our constipation technology is currently in a Phase 1 clinical trial, targeting completion in 1H’17.

What makes your technology so different?

Instead of fasting, and needing to consume a large volume of white, viscous, unpalatable fluid, our approach features simple, tasty bars and beverages that you consume during the 24 hours before the procedure.

When will your products reach the market?

The FDA regulates colon prep products, and we’re entering our Phase 3 trial. Forecasting is tricky, but our target is to secure approvals and launch by early 2019.

Where will I be able to purchase the colon prep kits?

When our products are FDA-approved, we expect that your physician will prescribe them, just as conventional prep kits are prescribed today.

New Colonoscopy Prep In Testing

Here is a possibly good news: better-tasting colonoscopy preps are under development and are in the testing stage.  My own personal experience has been that the prep I used ranks among the most foul-tasting things I have ever consumed, and I honestly couldn't finish every bit of it toward the end.  Luckily, taking 95% of it was sufficient for a good preparation, but I really struggled to keep it down and was always on the verge of throwing up.  If these new preps under development solve that problem, that's great, and perhaps the competition will stimulate existing brands to attempt some much-needed improvement.  And if this raises adherence to CRC screening, so much the better.

TAXPAYERS MONEY WILL BE FLUSHED

Twenty years from now, you’ll be more disappointed by the things you didn’t do than the ones you did do. So throw off the bowlines. Sail away from the safe harbor. Catch the trade winds in your sails. Explore. Dream. Discover.
Mark Twain


There is not too much of “explore, dream, discover” in Obama’s initiative about cancer, the Cancer Moonshot initiative. I have already written about it. Since my last commentary, a Blue Ribbon Panel was assembled, and this distinguished panel came up with ten recommendations.

Remember my prediction, the one that the $1 billion would go directly where the other billions of dollars have gone in the past 45 years? The money will go for CANCER TREATMENT, not PREVENTION. Yes, I was right, nine out of ten recommendations designate the money for treatment.

If the listed below recommendations were anonymously reviewed by any NIH NCI peer review panel, they would have been dismissed as not well justified, low impact, and catering to profit-driven interests.

Feast your mind on the following recommendations:

A. Establish a network for direct patient involvement: …this recommendation calls for cancer patients to join a new national network that … will provide them with a genetic profile of their cancer and let them “preregister” for clinical trials.

My response: Please, re-think the clinical trials first, then ask for more patient participation. There was an excellent idea on re-structuring the current "randomized controlled" clinical trials in the documentary “Surviving terminal cancer”.



B. Create a clinical trials network devoted exclusively to immunotherapy … for pediatric and adult cancers …to advance research in this area and could lead to new vaccines to prevent cancers of all types in children and adults.

My response: Where is the high impact in this maneuver? Also, I have not seen any rationale in this approach: how exactly would a clinical trials network result in new vaccines that prevent all cancers? Was this recommendation even written by a scientist or a sci-fi writer?

 

C. Develop ways to overcome resistance to therapy… this calls for establishment of multidisciplinary research teams to understand how drug resistance develops and find ways to prevent tumors from resisting the drugs meant to kill them.

My response: Really, the molecular mechanisms of drug resistance are extremely well studied. It is a matter of implementing the accumulated knowledge.

 
D. Build a national cancer data ecosystem… this would link many of the nation’s largest data repositories to enable one-stop, free access for researchers, doctors, and patients to share data on cancer and fuel faster progress.

My response: I am always suspicious when someone uses unusual combinations of words such as “national cancer data ecosystem”. Try to put it simply, for example: “implement obligatory sharing of data”. This is good, but how are we going to achieve it?
 


E. Intensify research on the major drivers of childhood cancers … intensifying research in cell biology, genomics, proteomics, and drug development would accelerate development of new therapies that target these cancer-causing proteins.

My response: Of course, we need to continue researching childhood cancers. I am not sure how this constitutes a novel and breakthrough recommendation? I assume we have been doing it all along.


F. Minimize cancer treatment’s debilitating side effects …this should support development of guidelines for managing patient-reported symptoms and side effects of cancer treatment in adults and children, with the goal of helping patients stay on their drug regimens and improve their quality of life.

My response: How about managing the health awareness and lifestyle factors that predispose to cancer instead? “Helping patients stay on their drug regimen”? Does this sound like trying to increase the profit for big pharma?



G. Expand use of proven prevention and early detection strategies…several cancer prevention and risk-reduction strategies have proven to be effective, including tobacco control, colorectal cancer screening, and HPV vaccination. The recommendation also calls for increasing testing for hereditary cancer syndromes in people with certain types of cancer and their family members, so those identified as high risk can begin early prevention or screening efforts.

My response: Out of the ten recommendations, this is THE ONLY one that deals with prevention, and YET, it does not mention the major lifestyle factors that contribute to cancer today: our sugar-laced diet, the physical inactivity, and the obesity. Tobacco use has been decreasing in the U.S. and we should continue doing whatever we have been doing about it.

Of course, the profit had to be factored even in a "prevention" recommendation: why not start excessively sequencing and screening, if someone could profit from it? Remember, the hereditary cancer syndromes account for maximum 20% of all cancers. The other 80% are mostly due to lifestyle, environment, age. Behavioral changes and educational efforts are implemental; however, they are not even mentioned here.


H. Mine past patient data to predict future patient outcomes: … we need to understand why patients with the same type and stage of cancer, and same treatment end up with different outcomes. The idea is that analyzing the tumor tissue from patients may discover genetic and other factors that impact response.

My response: We already know that amazingly diverse factors modulate the treatment response of individual patients. Instead, we should focus on the main factors/approaches that we know impact almost ALL cancer patients. How about examining the effect of ketogenic dietary regimens that could benefit more than 90% of all cancer patients? Or how about researching Coley's vaccine and why 40-50% of the advanced cancers were cured with this approach?


I. Develop a 3D cancer atlas: a web-based catalog of the genetic lesions and cellular interactions in tumor, immune, and other cells in the tumor microenvironment. The hope is that we will learn about the “evolution of tumors” and this will allow for developing predictive models of tumor progression and response to treatment.

My response: This is equivalent to going fishing into a land without any water body, not even a puddle. We already know that there is not only inter-individual heterogeneity of primary cancers, but also heterogeneity between the cells in the primary cancer in a patient, heterogeneity within the cells of a single metastasis, and between the cells of different metastases of the same individual. Why do we think that we can make sense of the cancer cell "insanity"? This expedition is hopeless. Instead, focus on the initial stages of neoplastic development, when we can really have an impact.
 

J. Develop new cancer technologies: increase the public–private sector collaboration to develop new tools or refine technologies (e.g., implantable microdosing devices that deliver drugs directly into a tumor to test their effectiveness, and advanced imaging technologies to study cancers at extremely high resolution).

My response: These new high-tech toys may not have any impact since the drugs used for the treatment would be the same. The only result will be the escalation of the cancer care cost.

Alcohol And Cancer

Paper analyzing the role of alcohol consumption in cancer:

Abstract

BACKGROUND AND AIMS:

There is increasing research evidence about the causal role of alcohol in cancer, accompanied by unclear and conflicting messages in the media. This paper aimed to clarify the strength of the evidence for alcohol as a cause of cancer, and the meaning of cause in this context.

METHODS:

Recent epidemiological and biological research on alcohol and cancer was reviewed and summarized, drawing upon published meta-analyses identified from the Medline database and the archives of the International Agency for Research on Cancer. More recent epidemiological studies not included in these publications were also reviewed. A brief description of the nature of causal inference in epidemiology was used to frame discussion of the strength of the evidence that alcohol causes cancer, and contrast this with the case for a protective association of alcohol with cardiovascular disease.

RESULTS:

The usual epidemiological understanding of a cause is a factor that increases the incidence of a condition in the population. In the context of a body of epidemiological evidence of an association of alcohol consumption with a disease, the inference that it is a causal association requires alternative explanations of the observed finding to be judged unlikely. Even without complete knowledge of biological mechanisms, the epidemiological evidence can support the judgement that alcohol causes cancer of the oropharynx, larynx, oesophagus, liver, colon, rectum and breast. The measured associations exhibit gradients of effect that are biologically plausible, and there is some evidence of reversibility of risk in laryngeal, pharyngeal and liver cancers when consumption ceases. The limitations of cohort studies mean that the true effects may be somewhat weaker or stronger than estimated currently, but are unlikely to be qualitatively different. The same, or similar, epidemiological studies also commonly report protection from cardiovascular disease associated with drinking but a high level of scepticism regarding these findings is now warranted.

CONCLUSIONS:

There is strong evidence that alcohol causes cancer at seven sites in the body and probably others. Current estimates suggest that alcohol-attributable cancers at these sites make up 5.8% of all cancer deaths world-wide. Confirmation of specific biological mechanisms by which alcohol increases the incidence of each type of cancer is not required to infer that alcohol is a cause.

So, alcohol consumption likely promotes cancer but skepticism is warranted about it being protective against cardiovascular disease.

I myself only consume (small) amounts of alcohol infrequently at holidays. I see no reason to be drinking alcohol on a regular basis.

Carbs and Cancer: Glycaemic Index and Lung Cancer

Is eating certain carbs as bad as smoking?

PITTSBURGH (KDKA) – You’ve heard that carbs can increase your waistline, but according to a new study they could be as bad for you as smoking cigarettes.
 

The study found carbs can actually raise the risk of lung cancer by some 49-percent.
 
Scientists found foods with a high glycaemic index, such as white bread, may increase the risks of cancer.
 
The report says glycaemic index is a measure of the quality of dietary carbohydrates – and is defined by how certain foods affect our blood sugar levels after eating.
 
The theory behind the study is that high-GI foods trigger higher levels of glucose and insulin in the blood, which in turn increase Insulin-Like Growth Factors (IGFs).
 
The study was conducted by the University of Texas MD Anderson Cancer Center.
 
Lead author on the study, Dr. Stephanie Melkonian says: “We observed a 49 percent increased risk of lung cancer among subjects with the highest daily GI compared to those with the lowest daily GI.”
 
The study says people should limit their intake of foods and beverages with a high GI.

So, in this study is was not total carbs per se that was the problem, but rather, the type of carbs - in other words a qualitative rather than strictly quantitative problem. Therefore, "white" and "starchy" carbs are a problem, by causing blood glucose spikes that result in higher levels of insulin and insulin-like growth factors. Whole wheat, etc, as much as non-starchy vegetables and many fruits, do not have the same effect. Although the problem is qualitative in that the type of carbs is what's most important, of course how much you eat of it will influence risk. Eating some occasional white bread and rice (which I for one try to avoid as much as possible) is likely not going to be as risky as stuffing your face with it every day, especially multiple times per day. Eating some potatoes won't kill you either. Again, it is a question of balance. For a variety of reasons independent of this study (obesity, diabetes, etc.) it is a good idea to limit levels of high glycaemic carbs. One does not have to completely eliminate them, but limit consumption , definitely, yes.

Gut Microbiota As A Colorectal Cancer Screening Tool

A proposed method for non-invasive colorectal cancer screening is to test the gut microbiota from stool samples; this is interesting, but obviously requires more development.  One possibility is that a combination of different non-invasive screening tools - fecal occult blood, gene testing from fecal matter, microbiota together with risk factors, etc. - can together provide sufficient accuracy and precision to be an effective screening combination.  Or else, "bite the bullet" and get the colonoscopy.  The abstract of this paper is reproduced below.

Recent studies have suggested that the gut microbiome may be an important factor in the development of colorectal cancer. Abnormalities in the gut microbiome have been reported in patients with colorectal cancer; however, this microbial community has not been explored as a potential screen for early-stage disease. We characterized the gut microbiome in patients from three clinical groups representing the stages of colorectal cancer development: healthy, adenoma, and carcinoma. Analysis of the gut microbiome from stool samples revealed both an enrichment and depletion of several bacterial populations associated with adenomas and carcinomas. Combined with known clinical risk factors of colorectal cancer (e.g., BMI, age, race), data from the gut microbiome significantly improved the ability to differentiate between healthy, adenoma, and carcinoma clinical groups relative to risk factors alone. Using Bayesian methods, we determined that using gut microbiome data as a screening tool improved the pretest to posttest probability of adenoma more than 50-fold. For example, the pretest probability in a 65-year-old was 0.17% and, after using the microbiome data, this increased to 10.67% (1 in 9 chance of having an adenoma). Taken together, the results of our study demonstrate the feasibility of using the composition of the gut microbiome to detect the presence of precancerous and cancerous lesions. Furthermore, these results support the need for more cross-sectional studies with diverse populations and linkage to other stool markers, dietary data, and personal health information. Cancer Prev Res; 1–10. ©2014 AACR.