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Cancer

Cancer is a heterogeneous group of more than 200 distinct diseases with very different etiologies, courses, and treatments; the popular simplification of "cancer" as a single entity is misleading and creates mistaken expectations about intervention… Read more.

32 factors with evidence, ordered from most to least effective. Information, not medical advice.

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*⏱ 2 min read

Cancer is the second leading cause of death in the world, and the success of treatment depends fundamentally on early detection; however, conventional screening and diagnostic approaches, which are usually based on tissue biopsies, have limitations that hinder their effectiveness, which has driven the development of liquid biopsies, an innovative technique that analyzes body fluids such as blood, urine, or cerebrospinal fluid for signs of cancer before tumors are clinically detectable.

Liquid biopsies analyze circulating tumor cells, circulating cell-free DNA, circulating tumor DNA, and circulating cell-free RNA that tumors release into the bloodstream through apoptosis, necrosis, and immune clearance; detection systems such as GRAIL's Galleri, which analyzes methylation patterns of cell-free DNA, can detect more than 50 types of cancer, although their real positive predictive value in a population with typical cancer prevalence is approximately 44%, not the 99% cited under laboratory conditions.

The importance of early detection and the challenges of precision

The average 5-year survival rate varies dramatically depending on the stage of the cancer at diagnosis: 71% for localized stage, 51% for regional stage, and only 14% for distant stage with metastasis, which underscores why detecting cancer while it is still small is so critical; however, medical imaging techniques can only detect tumors equal to or larger than 1 cm in diameter, and by then a tumor may already harbor a trillion cells and have altered its microenvironment.

False positives represent a major challenge in liquid biopsies: although Galleri claims a specificity rate of 99.5%, the real false-positive rate in clinical practice is higher because the positive predictive value of any test depends on the prevalence of the disease in the population, and in low-risk populations a highly specific test can still produce many false positives; for this reason liquid biopsies are best used to complement conventional imaging tests rather than replace them.

Applications beyond screening: treatment guidance and monitoring

Liquid biopsies offer significant advantages in guiding cancer treatment: they make it possible to detect actionable mutations in non-small cell lung cancer (EGFR), colorectal cancer (KRAS), and advanced breast cancer (PIK3CA) from a simple blood draw, without the need for tissue biopsies that can be invasive or technically impossible when the tumor is not accessible; and they can monitor treatment response in near real time, detecting changes in tumor burden earlier than conventional imaging methods.

Detection of drug resistance is another promising application: cancers acquire mutations over time that lead to resistance to treatments, and tissue biopsies are limited in frequency because of their invasiveness; in a study of 42 patients with gastrointestinal cancer, cell-free DNA analysis outperformed tissue biopsies in identifying clinically relevant resistance, with liquid biopsies detecting resistance not found in tissue samples in 78% of cases.

References

  1. Circulating tumor cells. doi:10.1146/annurev-med-010915-103022
  2. Cell-free DNA in cancer detection. doi:10.1038/nrc.2016.88
  3. Liquid biopsy biomarkers - overview. doi:10.1016/j.molcel.2016.12.002
  4. GRAIL Galleri test performance. doi:10.1016/j.annonc.2021.05.806
  5. Sensitivity and specificity of liquid biopsy meta-analysis. doi:10.1200/JCO.2020.38.15\_suppl.3027

*⏱ 2 min read

N-glycolylneuraminic acid, or Neu5Gc, is a sialic acid, a nine-carbon sugar molecule, produced by most non-human mammals; sialic acids play diverse roles such as mediating cell-cell interactions, triggering cell signaling cascades, and binding to pathogens, but humans do not produce Neu5Gc endogenously although small amounts are usually present in human urine, which indicates that the compound is obtained through the diet, with red meat and milk being the foods richest in Neu5Gc.

Because of its structural similarity to Neu5Ac, a sialic acid that the human body produces naturally, Neu5Gc is handled by the body's biochemical pathways as if it were its own, but the immune system recognizes it as foreign and produces antibodies against it; therefore, eating foods that contain Neu5Gc can trigger an immune response, activating inflammation and potentially providing a unique dietary link between the consumption of animal products and chronic diseases, especially atherosclerosis and cancer.

The evidence and its limitations

Studies in animal models show that Neu5Gc accumulates in human lung, pancreatic, and ovarian tumors, and that humanized Neu5Gc-deficient mice fed this compound and challenged with anti-Neu5Gc antibodies developed systemic inflammation with elevated IL-6 levels and a fivefold higher incidence of carcinomas after prolonged exposure; however, extrapolating these findings to humans is complicated because humans absorb much less dietary Neu5Gc than mice and eliminate it more quickly.

The picture is further complicated because a recent meta-analysis of 24 randomized controlled trials suggests that eating red meat daily does not influence cardiovascular risk biomarkers, and large population studies show that animal protein consumption was only associated with higher mortality rates when participants had at least one unhealthy lifestyle risk factor such as smoking, excessive alcohol consumption, physical inactivity, or overweight; the conclusion is that the risks of Neu5Gc, if they exist, probably manifest only in the context of a generally unhealthy lifestyle.

References

  1. Sialic acids in human health and disease. doi:10.1016/j.molmed.2008.06.002
  2. Human Uptake And Incorporation Of An Immunogenic Nonhuman Dietary Sialic Acid. doi:10.1073/pnas.2131556100
  3. Uniquely human evolution of sialic acid genetics and biology. doi:10.1073/pnas.0914634107
  4. Evidence For Human-Specific Mechanism For Diet And Antibody-Mediated Inflammation In Carcinoma Progression. doi:10.1073/pnas.0803943105
  5. A Red Meat-Derived Glycan Promotes Inflammation And Cancer Progression. doi:10.1073/pnas.1417508112
  6. Evidence For A Novel Human-Specific Xeno-Auto-Antibody Response Against Vascular Endothelium. doi:10.1182/blood-2009-05-220400

In depth

⏱ 3 min read

Cancer is a heterogeneous group of more than 200 distinct diseases with very different etiologies, courses, and treatments; the popular simplification of "cancer" as a single entity is misleading and produces mistaken expectations about supposedly universal interventions. The good news: approximately 40% of cancers are preventable by modifying known risk factors, and the combination of prevention, early detection, and modern treatment has dramatically improved survival rates in recent decades.

Main modifiable risk factors

Tobacco: causes approximately 20-30% of all cancer deaths; cancers of the lung, bladder, kidney, pancreas, stomach, colorectum, esophagus, mouth, pharynx, larynx, cervix, and breast. It is probably the single preventive intervention with the greatest impact.

Obesity: increases the risk of at least 13 types of cancer (postmenopausal breast, colorectal, endometrial, esophageal, kidney, pancreatic, liver, gallbladder, ovarian, myeloma, others).

Alcohol: any amount increases the risk of several cancers (breast, esophagus, liver, colorectal, head and neck). Modern recommendations are increasingly restrictive; "no safe amount" for cancer risk.

Ultra-processed diet: increases the risk of several cancers.

Processed meats: classified by IARC as a carcinogen (colorectal cancer). Excess red meat: probably carcinogenic.

Sedentary lifestyle.

Excessive sun exposure and sunburns: skin cancers.

Oncogenic infections: HPV (cervical, anal, and oropharyngeal cancers), HBV and HCV (hepatocellular), Helicobacter pylori (gastric), HIV (several). HPV and HBV vaccination prevents specific cancers.

Ionizing radiation: unnecessary X-rays, residential radon.

Environmental pollution: urban air, asbestos, certain industrial chemicals.

Screening: early detection that saves lives

  • Mammography: breast cancer (ages 50-69 in Spanish programs; varies by protocol).
  • Cervical cytology / HPV test: cervical cancer.
  • Fecal occult blood test or colonoscopy: colorectal cancer (ages 50-74).
  • Low-dose chest CT: lung cancer in long-term smokers.
  • PSA: prostate cancer (informed decision with the doctor).

Specific recommendations vary by country, age, sex, and individual risk factors. Adherence to screening is probably the preventive intervention with the greatest impact on cancer-specific mortality.

Nutritional interventions with population-level support

Mediterranean diet: support from prospective cohorts for several cancers.

High intake of varied vegetables and fruits.

Adequate dietary fiber: robust support for colorectal cancer.

Regular oily fish.

Limit processed meats; moderate red meat.

Limit alcohol.

Limit added sugars and ultra-processed foods.

Maintain a healthy weight.

Specific components with modest support in chemoprevention

Green tea polyphenols: with modest support in Asian cohorts.

Sulforaphane (broccoli and cruciferous vegetables): extensive preclinical support, preliminary clinical data in prostate cancer.

Lycopene (cooked tomato): modest support in prostate cancer.

Vitamin D: subclinical deficiencies associated with worse prognosis in several cancers; reasonable to correct.

Selenium: in areas with selenium-poor soil, supplementation has modest support; in regions with adequate intake, it offers no benefit.

Curcumin, resveratrol, EGCG, quercetin: extensive preclinical support, promising but not definitive clinical data.

Low-dose aspirin: support for preventing colorectal cancer in people with an indicated cardiovascular risk. Individualized risk-benefit balance.

What does NOT work

Modern clinical data have ruled out several popular claims: - Megadoses of vitamin C: no support in cancer prevention. - Megadoses of antioxidants: some studies suggest possible adverse effects in smokers (CARET, ATBC with beta-carotene). - "Alkaline diets": the body regulates its pH; it is not changed by diet in any physiologically relevant way. - "Miraculous" anticancer supplements: no rigorous clinical support. Take special care regarding interference with active cancer treatment.

When to see a doctor

Any persistent symptom without a clear explanation should be evaluated: unintentional weight loss, unexplained fatigue, persistent pain, changes in skin/moles, abnormal bleeding, sustained changes in bowel or urinary habits, palpable lumps, persistent cough, prolonged hoarseness, difficulty swallowing. Early detection changes trajectories.

The reasonable conclusion

The strongest cancer prevention combines: not smoking, a healthy weight, a Mediterranean diet (rich in plants, low in ultra-processed foods and processed meats), minimal alcohol, regular physical exercise, adequate sun protection, adherence to screening, and HPV and HBV vaccination. Specific nutritional components have modest support and are complements, not guarantees. In people with a cancer diagnosis, nutrition and supplementation should be coordinated with the oncology team to avoid interactions with treatment; "alternative treatments" without real clinical support are potentially dangerous because of the time lost and the compromised efficacy.

References

  1. World Cancer Research Fund / American Institute for Cancer Research (2018). Diet, nutrition, physical activity and cancer: a global perspective. Continuous Update Project Expert Report.
  2. Schwingshackl, L. et al. (2017). Adherence to Mediterranean diet and risk of cancer: a systematic review and meta-analysis of observational studies. Int J Cancer 140, 7. doi:10.1002/ijc.30509
  3. Aune, D. et al. (2017). Fruit and vegetable intake and the risk of cardiovascular disease, total cancer and all-cause mortality. Int J Epidemiol 46, 3. doi:10.1093/ije/dyw319
  4. Bouvard, V. et al. (2015). Carcinogenicity of consumption of red and processed meat. Lancet Oncol 16, 16. doi:10.1016/S1470-2045(15)00444-1
  5. GBD 2017 Risk Factor Collaborators (2018). Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks. Lancet 392, 10159. doi:10.1016/S0140-6736(18)32225-6
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Cancer

⏱ 3 min read

Cancer is a heterogeneous group of more than 200 distinct diseases with very different etiologies, courses, and treatments; the popular simplification of "cancer" as a single entity is misleading and produces mistaken expectations about supposedly universal interventions. The good news: approximately 40% of cancers are preventable by modifying known risk factors, and the combination of prevention, early detection, and modern treatment has dramatically improved survival rates in recent decades.

Main modifiable risk factors

Tobacco: causes approximately 20-30% of all cancer deaths; cancers of the lung, bladder, kidney, pancreas, stomach, colorectum, esophagus, mouth, pharynx, larynx, cervix, and breast. It is probably the single preventive intervention with the greatest impact.

Obesity: increases the risk of at least 13 types of cancer (postmenopausal breast, colorectal, endometrial, esophageal, kidney, pancreatic, liver, gallbladder, ovarian, myeloma, others).

Alcohol: any amount increases the risk of several cancers (breast, esophagus, liver, colorectal, head and neck). Modern recommendations are increasingly restrictive; "no safe amount" for cancer risk.

Ultra-processed diet: increases the risk of several cancers.

Processed meats: classified by IARC as a carcinogen (colorectal cancer). Excess red meat: probably carcinogenic.

Sedentary lifestyle.

Excessive sun exposure and sunburns: skin cancers.

Oncogenic infections: HPV (cervical, anal, and oropharyngeal cancers), HBV and HCV (hepatocellular), Helicobacter pylori (gastric), HIV (several). HPV and HBV vaccination prevents specific cancers.

Ionizing radiation: unnecessary X-rays, residential radon.

Environmental pollution: urban air, asbestos, certain industrial chemicals.

Screening: early detection that saves lives

Specific recommendations vary by country, age, sex, and individual risk factors. Adherence to screening is probably the preventive intervention with the greatest impact on cancer-specific mortality.

Nutritional interventions with population-level support

Mediterranean diet: support from prospective cohorts for several cancers.

High intake of varied vegetables and fruits.

Adequate dietary fiber: robust support for colorectal cancer.

Regular oily fish.

Limit processed meats; moderate red meat.

Limit alcohol.

Limit added sugars and ultra-processed foods.

Maintain a healthy weight.

Specific components with modest support in chemoprevention

Green tea polyphenols: with modest support in Asian cohorts.

Sulforaphane (broccoli and cruciferous vegetables): extensive preclinical support, preliminary clinical data in prostate cancer.

Lycopene (cooked tomato): modest support in prostate cancer.

Vitamin D: subclinical deficiencies associated with worse prognosis in several cancers; reasonable to correct.

Selenium: in areas with selenium-poor soil, supplementation has modest support; in regions with adequate intake, it offers no benefit.

Curcumin, resveratrol, EGCG, quercetin: extensive preclinical support, promising but not definitive clinical data.

Low-dose aspirin: support for preventing colorectal cancer in people with an indicated cardiovascular risk. Individualized risk-benefit balance.

What does NOT work

Modern clinical data have ruled out several popular claims: - Megadoses of vitamin C: no support in cancer prevention. - Megadoses of antioxidants: some studies suggest possible adverse effects in smokers (CARET, ATBC with beta-carotene). - "Alkaline diets": the body regulates its pH; it is not changed by diet in any physiologically relevant way. - "Miraculous" anticancer supplements: no rigorous clinical support. Take special care regarding interference with active cancer treatment.

When to see a doctor

Any persistent symptom without a clear explanation should be evaluated: unintentional weight loss, unexplained fatigue, persistent pain, changes in skin/moles, abnormal bleeding, sustained changes in bowel or urinary habits, palpable lumps, persistent cough, prolonged hoarseness, difficulty swallowing. Early detection changes trajectories.

The reasonable conclusion

The strongest cancer prevention combines: not smoking, a healthy weight, a Mediterranean diet (rich in plants, low in ultra-processed foods and processed meats), minimal alcohol, regular physical exercise, adequate sun protection, adherence to screening, and HPV and HBV vaccination. Specific nutritional components have modest support and are complements, not guarantees. In people with a cancer diagnosis, nutrition and supplementation should be coordinated with the oncology team to avoid interactions with treatment; "alternative treatments" without real clinical support are potentially dangerous because of the time lost and the compromised efficacy.

References

  1. World Cancer Research Fund / American Institute for Cancer Research (2018). Diet, nutrition, physical activity and cancer: a global perspective. Continuous Update Project Expert Report.
  2. Schwingshackl, L. et al. (2017). Adherence to Mediterranean diet and risk of cancer: a systematic review and meta-analysis of observational studies. Int J Cancer 140, 7. doi:10.1002/ijc.30509
  3. Aune, D. et al. (2017). Fruit and vegetable intake and the risk of cardiovascular disease, total cancer and all-cause mortality. Int J Epidemiol 46, 3. doi:10.1093/ije/dyw319
  4. Bouvard, V. et al. (2015). Carcinogenicity of consumption of red and processed meat. Lancet Oncol 16, 16. doi:10.1016/S1470-2045(15)00444-1
  5. GBD 2017 Risk Factor Collaborators (2018). Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks. Lancet 392, 10159. doi:10.1016/S0140-6736(18)32225-6