Vitamin D Against Colon Cancer

Roles of vitamin D in colon cancer prevention, abstract:

Colorectal cancer (CRC) is the neoplasia that is most frequently associated with vitamin D deficiency in epidemiological and observational studies in terms of incidence and mortality. Many mechanistic studies show that the active vitamin D metabolite (1α,25-dihydroxyvitamin D3 or calcitriol) inhibits proliferation and promotes epithelial differentiation of human colon carcinoma cell lines that express vitamin D receptor (VDR) via the regulation of a high number of genes. A key action underlining this effect is the multilevel inhibition of the Wnt/β-catenin signaling pathway, whose abnormal activation in colon epithelial cells initiates and promotes CRC. Recently, our group has shown that calcitriol modulates gene expression and inhibits protumoral properties of patient-derived colon cancer-associated fibroblasts (CAFs). Accordingly, high VDR expression in tumor stromal fibroblasts is associated with longer survival of CRC patients. Moreover, many types of immune cells express VDR and are regulated by calcitriol, which probably contributes to its action against CRC. Given the role attributed to the intestinal microbiota in CRC and the finding that it is altered by vitamin D deficiency, an indirect antitumoral effect of calcitriol is also plausible at this level. In summary, calcitriol has an array of potential protective effects against CRC by acting on carcinoma cells, CAFs, immune cells and probably also the gut microbiota.

Your Risk for Colon Cancer

50,630:
this is the projected number of colorectal cancer (CRC) -related deaths for 2018 in the U.S. Only lung cancer-related deaths exceed this number.

How does CRC start? It begins as a benign growth – polyp / adenoma. The most frequent initiating mutation is in the APC gene, and less frequently - in the proteins beta-Catenin, Axin, and KRAS. Given sufficient time - approximately 10 years - and the right mutations (i.e., mutations that allow self-sufficiency in growth signaling, resistance to apoptosis, potential for unlimited growth, etc), malignancy develops.

Once the malignancy has established itself, cure is unlikely. Therefore, the best approach is this of prevention; the words of Ben Franklin are still valid:

… an ounce of prevention is worth a pound of cure…

The power of prevention is best understood when we look at the leading causes of death for the past 100 years. NEJM has published a great review that summarizes the ten leading causes of death in the U.S. since 1900. If we compare 1900 to 2010, we will find that the three biggest killers in 1900 were the gastrointestinal infections, pneumonia, and TB.  However, these were no longer the biggest killers in 2010 (the last year in the NEJM review).

How did we achieve that? Sanitation, better nutrition, vaccination, and antibiotics. Except for the antibiotics, the rest of the measures/changes were preventive.

Since the 1960s we have also seen reduction in heart disease-associated deaths due to prevention with medications that control blood pressure and cholesterol.

The lesson is that any significant victory against a disease is achieved through preventive strategies. There is no doubt in my mind that we will claim a significant victory against cancer, when we dedicate more financial resources to prevention. Cervical cancer is the perfect example how prevention through screening and vaccines reduces cancer deaths.

However, can we prevent colorectal cancer (CRC)? Obviously, screening is one answer; although quite invasive, colonoscopy detects early lesions. What else can we do? The American Institute for Cancer Research (AICR) has estimated that approximately 45% of all CRC cases can be prevented mostly through lifestyle changes. The institute has come up with five simple recommendations … that may slash the number of CRC cases by half! The problem with all these recommendations is that they require self-discipline.

The increased intake of fiber is one of the recommendations. Although the topic has been controversial for the past few decades, in 2003, two massive prospective epidemiological studies (one from Europe and one from the U.S.) concluded that fiber does protect against colon cancer: increasing the intake of fiber from 15 g to 35 g results in 40% decrease in risk.

Here is the summary of one of the studies:

Lancet 2003 May 3;361(9368):1496-501.Bingham SA:  
We prospectively examined the association between dietary fibre intake and incidence of colorectal cancer in 519978 individuals aged 25-70 years in ten European countries. Participants completed a dietary questionnaire in 1992-98 and were followed up for cancer incidence. …data for 1065 reported cases of colorectal cancer were included in the analysis. Dietary fibre in foods was inversely related to incidence of large bowel cancer (adjusted relative risk 0.75 [95% CI 0.59-0.95] for the highest versus lowest quintile of intake), the protective effect being greatest for the left side of the colon, and least for the rectum. After calibration with more detailed dietary data, the adjusted relative risk for the highest versus lowest quintile of fibre from food intake was 0.58 (0.41-0.85). No food source of fibre was significantly more protective than others, and non-food supplement sources of fibre were not investigated. In populations with low average intake of dietary fibre, an approximate doubling of total fibre intake from foods could reduce the risk of colorectal cancer by 40%.

In 2011, AICR and the continuous update project announced that the protective effect of fiber against colon cancer is upgraded from probable to convincing.

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.

Omega-3 Fatty Acids And Prevention Of Colorectal Cancer Recurrence

Omega-3 fatty acids in (recurrent) cancer prevention.

Increasing evidence supports the contention that many malignancies, including sporadic colorectal cancer, are driven by the self-renewing, chemotherapy-resistant cancer stem/stem-like cells (CSC/CSLC), underscoring the need for improved preventive and therapeutic strategies targeting CSCs/CSLCs. Omega-3 polyunsaturated fatty acids (ω-3 PUFA), have been reported to inhibit the growth of primary tumors, but their potential as a preventive agent for recurring cancers is unexplored. The primary objectives of this investigation are (i) to examine whether eicosapentaenoic acid (EPA; one of the ω-3 PUFA) synergizes with FuOx (5-FU+Oxaliplatin), the backbone of colon cancer chemotherapy, and (ii) whether EPA by itself or in combination with conventional chemotherapy prevents the recurrence of colon cancer via eliminating/suppressing CSCs/CSLCs. FuOx-resistant (chemoresistant; CR) colon cancer cells, highly enriched in CSCs, were used for this study. Although EPA alone was effective, combination of EPA and FuOx was more potent in (i) inhibiting cell growth, colonosphere formation, and sphere-forming frequency, (ii) increasing sphere disintegration, (iii) suppressing the growth of SCID mice xenografts of CR colon cancer cells, and (iv) decreasing proinflammatory metabolites in mice. In addition, EPA + FuOx caused a reduction in CSC/CSLC population. The growth reduction by this regimen is the result of increased apoptosis as evidenced by PARP cleavage. Furthermore, increased pPTEN, decreased pAkt, normalization of β-catenin expression, localization, and transcriptional activity by EPA suggests a role for the PTEN-Akt axis and Wnt signaling in regulating this process. Our data suggest that EPA by itself or in combination with FuOx could be an effective preventive strategy for recurring colorectal cancer.

These findings suggest even more health benefits for omega-3 fatty acids.  It would seem that reasonable consumption of certain polyunsaturated fats has not only cardiovascular benefits, but cancer prevention benefits as well.

Lifestyle versus predisposition: scratching my head

Have you heard about the health care systems in the U.S. that have started to sequence millions of genomes in order to unearth a few predisposition genes? Millions of dollars are now poured into this endeavor. As a result, we will eventually connect the presence of some gene variants with increased risk of conditions X, Y and Z, ... and we will know that Joe Smith carries a predisposition gene for condition Z.

The fact that these are only PREDISPOSITION genes tells you that LIFESTYLE may or may not allow for conditions X, Y, and Z to be developed. Then the logical question is, why are we so complacent about our current disease-permissive lifestyle? Should not we tackle unhealthy habits with the same enthusiasm (and the same amount of funds/resources) as the ones with which we embark on massive sequencing efforts? Is it cost-effective to allow the average American to play DARE by practicing the most disease-permissive lifestyle in the history of humankind?

Under ideal circumstances, in taking care of each individual, the health care system should combine the implementation of healthy habits along with the knowledge of the predisposition genes of the individual. Platforms such as PatientsLikeMe should match sequencing data input with physical/physiological data and health markers/outcomes. Prospective analyses of such data will suggest how "tweaks" in the lifestyle can prevent the establishment of conditions to which some are predisposed.

Since we are faraway from the ideal situation, it seems that educating the Americans in healthy prevention-oriented lifestyle is more economically sound than massive sequencing of a million human genomes. What do you think?

Berries Against Cancer

Something to consider:

Colon cancer is one of the most prevalent diseases across the world. Numerous epidemiological studies indicate that diets rich in fruit, such as berries, provide significant health benefits against several types of cancer, including colon cancer. The anticancer activities of berries are attributed to their high content of phytochemicals and to their relevant antioxidant properties. In vitro and in vivostudies have demonstrated that berries and their bioactive components exert therapeutic and preventive effects against colon cancer by the suppression of inflammation, oxidative stress, proliferation and angiogenesis, through the modulation of multiple signaling pathways such as NF-κB, Wnt/β-catenin, PI3K/AKT/PKB/mTOR, and ERK/MAPK. Based on the exciting outcomes of preclinical studies, a few berries have advanced to the clinical phase. A limited number of human studies have shown that consumption of berries can prevent colorectal cancer, especially in patients at high risk (familial adenopolyposis or aberrant crypt foci, and inflammatory bowel diseases). In this review, we aim to highlight the findings of berries and their bioactive compounds in colon cancer from in vitro and in vivo studies, both on animals and humans. Thus, this review could be a useful step towards the next phase of berry research in colon cancer

Vitamin D Deficiency and the Colon

Deficiency of vitamin D can promote colon inflammation and colon cancer.

Epidemiological studies showed that 1,25-Dihydroxyvitamin D[1,25(OH)2D3] insufficiency appears to be associated with aging and colon cancer while underlying biological mechanisms remain largely unknown. Inflammatory bowel disease is one of the risk factors for colon cancer. In this study, we investigated whether 1,25(OH)2D3 deficiency has an impact on the colon of 25-hydroxyvitamin D 1α-hydroxylase knockout [Cyp27b1-/-] mice fed on a rescue diet (high calcium, phosphate, and lactose) from weaning to 10 months of age. We found that 1,25(OH)2D3 deficient mice displayed significant colon inflammation phenotypes including shortened colon length, thinned and disordered mucosal structure, and inflammatory cell infiltration. DNA damage, cellular senescence and the production of senescence-associated inflammatory cytokines were also increased significantly in the colon of Cyp27b1-/-mice. Furthermore, the levels of ROS in the colonwere increased significantly, whereas the expression levels of antioxidative genes were down-regulated dramatically in the colon of Cyp27b1-/-mice. Taken together, our results demonstrated that 1,25(OH)2D3 deficiency could induce colon inflammation, which may result from increased oxidative stress and DNA damage, subsequently, induced cell senescence and overproduction of senescence-associated secretory factors. Therefore, our findings suggest that 1,25(OH)2D3 may play an important role in preventing the development and progression of colon inflammation and colon cancer.

Of course, too much of any vitamin or mineral is not good either. Strive for balance and obtain them from natural food sources (rather than supplements) if possible.  Some sunlight can help with vitamin D - but beware of too much exposure there as well (skin cancer threat).

Possible Advances For Non-Invasive Colorectal Cancer Screening

For those who avoid the colonoscopy because of its invasive nature, here is a sample of some research in the field of detection.

BACKGROUND: 

Colorectal cancer (CRC) is one of the most common causes of cancer-related death around the world. MicroRNAs (miRNAs) are small non-coding RNAs that often are abnormally expressed in tumors. Detection and quantitation of miRNAs may provide information for the screening and early diagnosis of CRC.

OBJECTIVES:

The objective of our study was to determine whether fecal microRNAs (miR-29a, miR-145, miR-223, miR-224) could be used as biomarkers for the screening and early diagnosis of colorectal cancer.

METHODS: 

We carried out a retrospective analysis of the miRNAs in fecal samples from 80 CRC patients and 51 normal controls. The levels of 4 miRNAs (miR-29a, miR-145, miR-223, and miR-224) were quantitated using the SYBR Green miScript PCR system and 2 - Δ Δ Ct method.

RESULTS:

Our data indicated that the expression levels of miR-29a (p< 0.001), miR-223 (p< 0.001) and miR-224 (p< 0.001) are significantly lower in feces from CRC patients than these from normal volunteers, whereas their miR-145 levels are not significantly different (p= 0.59). Interestingly, the level of miR-29a (p< 0.001) in feces from individuals with rectum cancer is also significantly higher than that from patients with colon cancer.

CONCLUSION: 

The reduced expression of miR-29a, miR-223, and miR-224 in the feces from CRC patients could be an informative biomarker for screening and early diagnosis of CRC.

As recent posts have made clear, I have had my colonoscopy done, but I understand that many people want to avoid it. Any type of detection, even the blood stool tests, is better than nothing, and non-invasive testing continues to become more sophisticated.

Electronic Cleansing For Virtual Colonoscopy

A study says:

Electronic cleansing is an image post processing technique in which the tagged colonic content is subtracted from colon using CTC images. There are post processing artefacts, like: 1) soft tissue degradation; 2) incomplete cleansing; 3) misclassification of polyp due to pseudo enhanced voxels; and 4) pseudo soft tissue structures. The objective of the study was to subtract the tagged coloniccontent without losing the soft tissue structures. This paper proposes a novel adaptive method to solve the first three problems using a multi-step algorithm. It uses a new edge model-based method which involves colon segmentation, priori information of Hounsfield units (HU) of different colonic contents at specific tube voltages, subtracting the tagging materials, restoring the soft tissue structures based on selective HU, removing boundary between air-contrast, and applying a filter to clean minute particles due to improperly tagged endoluminal fluids which appear as noise. The main finding of the study was submerged soft tissue structures were absolutely preserved and the pseudo enhanced intensities were corrected without any artifact. The method was implemented with multithreading for parallel processing in a high performance computer. The technique was applied on a fecal tagged dataset (30 patients) where the tagging agent was not completely removed from colon. The results were then qualitatively validated by radiologists for any image processing artifacts.

This would seem to eliminate the need for extensive bowel cleansing; instead a dye would be consumed that would stain fecal matter, which could then be electronically subtracted from the image. Imaging ("virtual") colonoscopy is an alternative to the “real-life” version. Advantages being that it is less invasive and eliminates most of the potential side effects; negatives are that you would need regular colonoscopy if the imaging found something, and it is not offered at many locations. Then there is the radiation exposure, and whether or not you are comfortable with imaging accuracy vs. direct visualization (although some studies put accuracy as high, but those were with bowel cleansing).

Colonoscopy In Old Age: What Best to Measure?

A paper looked at the utility of having patients 75+ years old have colonoscopies, which goes against current recommendations.

Among patients 76-85 years old in the United States, colonoscopy use was associated with decreased risks of both distal and proximal CRC, with a smaller risk reduction in distal colon. Due to inherent limitations associated with our retrospective design, future prospective studies are needed to validate these findings.

It is not surprising that a cohort of patients getting colonoscopies - the "gold standard" for colon cancer screening - will exhibit decreased risk for that disease.

But the better measurement would have been - did these patients end up living significantly longer? Did they have better morbidity and mortality? Were there tangible long-term benefits to compensate for the risk (old patients have a higher risk of side effects from colonoscopy that those in the 50-70 age range), cost, and inconvenience of the procedure at such an advanced age?

The recommendations against colonoscopy for age 75+ is not because folks think there is no disease risk at that age, it is because the thought is that these patients will most likely die of other causes and that the cost:benefit ratio for this class of patients is skewed in the direction of greater cost and less benefit.

Health Benefits of Mulberry Fruit

Here is a study suggesting that mulberry fruit can have positive effects against inflammation, colitis, and cancer:

Here, we investigated the impact of mulberry fruit (MBF) extracts on lipopolysaccharide (LPS)-induced inflammatory responses in RAW 264.7 macrophages, and the therapeutic efficacy of MBF diet in mice with dextran sulfate sodium (DSS)-induced acute colitis and MUC2(-/-) mice with colorectal cancer. In vitro, LPS-induced nitric oxide (NO) production was significantly inhibited by MBF extracts via suppressing the expression of proinflammatory molecules, including inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-1 beta (IL-β) and IL-6. Particularly, a dose-dependent inhibition on LPS-induced inflammatory responses was observed following treatment with MBF dichloromethane extract (MBF-DE), in which linoleic acid and ethyl linolenate were identified as two active compounds. Moreover, we elucidated that MBF-DE attenuated LPS-induced inflammatory responses by blocking activation of both NF-κB/p65 and pERK/MAPK pathways. In vivo, DSS-induced acute colitis was significantly ameliorated in MBF-fed mice as gauged by weight loss, colon morphology and histological damage. In addition, MBF-fed MUC2(-/-) mice displayed significant decrease in intestinal tumor and inflammation incidence compared to control diet-fed group. Overall, our results demonstrated that MBF suppressed the development of intestinal inflammation and tumorgenesis both in vitro and in vivo, and supports the potential of MBF as a therapeutic functional food for testing in human clinical trials.

Eating a diet high in fruits and vegetables seems to be a "can't lose" proposition for most - likely, all - people. Add mulberry fruit to the list of those plant-based foods you should consider eating.

Cancer Prevention Diet

Cancer prevention diet and other lifestyle tips: 

1. Be as lean as possible without becoming underweight. Weight gain, overweight and obesity increases the risk of a number of cancers, including bowel, breast, prostate, pancreatic, endometrial, kidney, gallbladder, oesophageal, and ovarian cancers.

2. Be physically active for at least 30 minutes every day. Physical activity decreases the risk of colon, endometrial, and postmenopausal breast cancer. As fitness improves, aim for 60 minutes or more of moderate, or for 30 minutes or more of vigorous, physical activity every day. 

3. Avoid sugary drinks and limit consumption of energy-dense food. Foods that are high in fats, added sugars, and/or low in fiber, such as many fast and convenience foods, as well as sodas and energy drinks, promote weight gain that is associated with a higher cancer risk.

4. Eat more of a variety of vegetables, fruits, whole grains, and pulses such as beans.

5. Limit consumption of red meats (such as beef, pork and lamb) and avoid processed meats.

6. Limit alcoholic drinks. Limit consumption to no more than two drinks a day for men and one drink a day for women.

7. Limit consumption of salt and avoid moldy grains and cereals. Limit consumption of processed foods with added salt to ensure an intake of less than 2.4g sodium a day. Do not eat moldy cereals (grains) or pulses (legumes).

8. Where possible, aim to meet nutritional needs through diet alone, instead of using supplements to try to protect against cancer.

9. It is best for mothers to breastfeed exclusively for up to 6 months and then add other liquids and foods. Babies who are breastfed are less likely to be overweight as children or adults.

10. After treatment, cancer survivors should follow the recommendations for cancer prevention. Follow the recommendations for diet, healthy weight, and physical activity from your doctor or trained professional.

As regards fruit and vegetables:

It comes down to this: Fruit and vegetables have less fat, more fiber, and more cancer-fighting nutrients. These three elements work together to support your immune system and help your body fight off cancer. Currently, most people are falling short of the recommended daily minimum of five servings of fruit and vegetables. In fact, most of us need to double the amount we currently eat to stay healthy and help prevent or fight cancer.

I agree with the recommendations, but I wonder. If every American wanted to eat this way, do we have the fruit and vegetable growing, harvesting, and shipping capacity to make it all possible?

Musings, Part I: Become your own hero

...Because, the hero from the   stories may never come

Americans are very optimistic people, with a firm belief in heroism, but is this always good? Is the optimism unfounded and where does it come from? Have you noticed that we, the Americans, are perpetually entranced by the glory of last-minute interventions? 

Here they are: the wail of the ambulance saving the sick, the rush of the doctors answering code blue, the explosive disabled at the last second, and the law officer apprehending the villain at the last moment… All of these eleventh-hour solutions bring thrill, joy, and elation. We also like to read about last-minute miracles. We delight in heroes of fiction, movies, songs, folk legends and fairy tales, as they all perform the last-minute ritual of SAVING. We grew up with the on-time sweep by Superman and the handsome youth killing the dragon just before the beast releases deadly fire on the innocent.  

We are searching for, and expecting, the same type of miracles in our lives. Our fascination with cancer cure is connected to this ingrained psychology of miracle-expectation. The obsession with cancer treatment and cure, mainstream or alternative, is all over Internet, newspapers, TV, movies and books. It will be difficult to re-adjust this attitude. It is time, however, to realize that even if heroes who “cure” cancer existed, it would be better to prevent the disease.  It is time to realize that if there is no health crisis, there will be no need of a hero. In fact, we all can become heroes by preventing our own health crisis, and managing whatever is under our control. Preventing a crisis in a long run is the true, but stealthy, heroism. This stealthy heroism manifests wisdom, initiative, and bravery. Not foreseeing a health crisis, however, and acting at the last moment, equates to stupidity, ignorance and impulsiveness. Think about it:

• One in five adult Americans smoke.

• Two in three adult Americans are overweight or obese.

• One in two adult Americans has diabetes or pre-diabetes. 

• One in two or three Americans will be diagnosed with cancer. 

How many more warnings do we need? In fact, the health crisis has been unfolding for the past 20 years. The stealth heroes have never showed up. Let's hope that the last-minute heroes make an appearance.

Musings - part II explains why being healthy is a question of freedom.

If you do not get cancer, you are not going to die from it…

AICR, Cancer Prevention: Putting it Together

The estimate of the American Cancer Society is that in 2015, 312,150 men and 277,280 women in the U.S. will die from cancer. This death toll is equivalent to that resulting from three 747s airplanes crashing DAILY.  If this hypothetical flight tragedy were to take place every day, and we knew how to prevent up to 75% of the passenger deaths, do you think that we would not have acted immediately?  And yet, despite the fact that we know how to prevent up to 75% of all cancers from occurring, we, as a society, do not act upon our knowledge.  By not implementing cancer prevention, we consciously fail more than 1,000 people every day.

What is cancer prevention? It means blocking or eliminating the factors that cause the disease, or detecting the disease before it becomes incurable. It has been estimated that we can prevent up to 75% of all cancers with what we know today. Therefore, even without further advancement in cancer research, we could have a major control over the disease. Why are we not doing it?
 

One answer comes from the recent PBS documentary“The Emperor of All Maladies”.  At approximately minute 41 in part three, Dr. Robert Weinberg, one of the most prominent cancer researchers today, states that although prevention is one of the most powerful approaches against cancer, researchers like him tend to disregard prevention because it is not “intellectually stimulating and exciting.” Further, he explains: “Persuading somebody to quit smoking is ultimately a behavioral, a psychological exercise, has nothing to do with molecules and genes and cells. And so people like me are essentially uninterested in it, in spite of the fact that stopping people smoking will have vastly more effect on cancer mortality than anything I could hope to do in my own lifetime.”

In addition to not being “intellectually stimulating,” cancer prevention is not financially stimulating.  Dr. Vogelstein and his colleagues think that: “The reasons that society invests so much more in research on cures for advanced cancers than on prevention or early detection are complex. Economic issues play a part: New drugs are far more lucrative for industry than new tests, and large individual costs for treating patients with advanced disease have become acceptable, even in developing countries. “We should applaud the courage of these cancer researchers, who finally named one of the major reasons for the lack of cancer prevention: lack of profit.  


Profit and myopic focus on cure rather than prevention dictate the effort of most U.S. cancer researchers, the pharmaceutical industry, the government-supported National Cancer Institute, and even national “non-profit” organizations that many of us support, such as the American Cancer Society (ACS) and the American Association for Cancer Research (AACR).  The small fraction of their budgets dedicated to prevention proves that cancer prevention is the “unwanted child” of these organizations. In 2015, AACR cancelled their annual “International Conference on Frontiers in Cancer Prevention Research.” I suspect that the attendance became so low in the past few years that it makes no sense to organize this meeting on an annual basis. According to ACS, approximately 13.6% of its budget in 2012 went for cancer prevention information and education; meanwhile, 26% went for supporting the functions of the organization. Even our taxpayer/government-supported National Institutes of Health do not emphasize cancer prevention.

The only prominent U.S. organization that still takes the war on cancer seriously is the American Institute for Cancer Research (AICR), with 100% of its effort dedicated to prevention.  AICR (in partnership with the World Cancer Research Fund International) is one of the few world organizations that consistently reach out to the population with recommendations on cancer prevention.

If the structure of our society is geared toward treatment rather than prevention, and yet, only prevention could make a major difference, what should we do? Should we start a relentless campaign on educating everyone about healthy lifestyles? Should the government and the health insurance companies offer incentives for cancer prevention adherence or impose disincentives for non-compliance? What is the right direction?