Clinical Knowledge Summary: Cancer Risk Reduction (Longevity Medicine)

 

1. Scope


Covered: Evidence-based and emerging interventions to reduce incident cancer and cancer mortality in adults seen in a private UK longevity clinic, working adjunctively to NHS primary and secondary care. Includes lifestyle interventions (physical activity, weight management, alcohol, smoking, diet), pharmacological chemoprevention (aspirin, metformin, GLP-1 receptor agonists), weight-loss surgery, vaccination (HPV), vitamin D, high-risk hereditary chemoprevention (Lynch syndrome), and experimental geroscience agents (rapamycin, senolytics).

Not covered: Detailed organised cancer-screening protocols (NHS bowel, breast, cervical, targeted lung screening), tumour-specific treatment, germline testing pathways, and radiological screening (e.g. whole-body MRI) — these are signposted but not the focus. This document does not replace NHS screening or specialist genetics referral.

Overarching principle: The largest, most certain reductions in cancer risk come from established modifiable factors (tobacco, alcohol, adiposity, physical inactivity) — not from supplements or off-label drugs. Chemoprevention should be individualised and, outside licensed/guideline indications, offered only with explicit informed consent and clear documentation.



2. Background and pathophysiology

Cancer is an age-related disease: two-thirds of new diagnoses occur in people ≥60 years.[1] Ageing biology and carcinogenesis share overlapping mechanisms, providing the rationale for a longevity-medicine approach.

Key human-relevant mechanisms:

– Adiposity-driven carcinogenesis — excess adipose tissue causes chronic inflammation (IL-6, TNF-α, prostaglandin E2), hyperinsulinaemia/IGF-1 signalling, raised sex-steroids, adipokine dysregulation, and immune suppression; obesity is convincingly linked to ≥13 cancers and ~10% of new diagnoses.[2]

– Insulin/IGF-1 and mTOR signalling — hyperinsulinaemia promotes tumour proliferation; AMPK activation and mTOR inhibition are the proposed anti-neoplastic mechanisms of metformin and rapalogs.[3][4]

– Inflammation and platelet/COX pathways — aspirin inhibits prostaglandin synthesis and platelet-derived thromboxane A2 (a T-cell suppressor); anti-metastatic platelet effects may explain mortality benefit.[1][5]

– Direct genotoxicity — alcohol/acetaldehyde (Group 1 carcinogen) and tobacco carcinogens cause DNA damage.[6][7]

– Immunosenescence and “inflammaging” — age-related immune decline may attenuate chemoprevention efficacy in older adults (a plausible explanation for divergent aspirin effects by age).[1]

Preclinical only (mechanistic plausibility, no human incidence data):

– Cellular senescence / SASP — senescent-cell accumulation drives age-related dysfunction; senolytics (dasatinib+quercetin, fisetin) extend lifespan and reduce organ dysfunction in mice.[8][9]

– mTOR inhibition (rapamycin) — the most reproducible cancer-delaying agent in murine models; low-dose rapamycin reduces DNA-damage-induced senescence markers (p21) in human immune cells but has no human cancer-incidence outcome data.[4][10]



3. Evidence base and grading

GRADE-style certainty (High/Moderate/Low/Very low) and strength of recommendation for each intervention–outcome pair.

Smoking cessation → cancer incidence and mortality

– Evidence statement: Consistent large cohort data and umbrella reviews show cessation reduces all-site cancer (aHR ~0.83 at ≥10–15 yrs), lung cancer (aHR ~0.58), and cancer/all-cause mortality; benefit at any quit age, greatest before age 40. RCT evidence exists for cessation interventions.[11][12][13]

– Certainty: High (biological gradient, dose-response, consistency; residual “sick-quitter” confounding minor).

– Recommendation: Strong recommendation — the single most important cancer-prevention intervention.

Alcohol reduction/cessation → alcohol-related cancers

– Evidence statement: Alcohol is a Group 1 carcinogen (oral, pharyngeal, laryngeal, oesophageal SCC, hepatocellular, colorectal, female breast). IARC judged sufficient evidence that reduction/cessation lowers oral and oesophageal cancer risk; large cohorts show reduced drinking lowers alcohol-related and all-cancer incidence. No safe threshold is established; breast cancer risk rises from any intake.[6][14][15][16]

– Certainty: Moderate (observational; “sick-quitter” bias, but consistent with mechanistic reversibility).

– Recommendation: Strong recommendation to minimise intake; frame as no risk-free level.

Physical activity → cancer incidence and mortality

– Evidence statement: Strong evidence (ACSM/WCRF) for reduced risk of bladder, breast, colon, endometrial, oesophageal adenocarcinoma, gastric, and renal cancers (RR reductions ~10–20%), with dose-response. Post-diagnosis activity associated with 40–50% lower mortality for breast/colon/prostate cancer (observational). Evidence is predominantly cohort-based (no RCTs with cancer endpoints).[17][18]

– Certainty: Moderate (large consistent cohorts, dose-response, plausible mechanisms; indirectness/confounding limit to moderate).

– Recommendation: Strong recommendation.

Weight loss — bariatric/metabolic surgery → obesity-associated cancer

– Evidence statement: Matched cohort (SPLENDID, n=30,318) — 32% lower obesity-associated cancer (HR 0.68) and 48% lower cancer mortality (HR 0.52); SOS study HR 0.67. Benefit strongest for endometrial cancer; requires >20% and sustained weight loss; curves separate ~6 years. No RCT (not feasible).[19]

– Certainty: Moderate (well-matched large cohorts, dose-response, mortality endpoint) for obesity-associated cancer overall; Low for most individual sites.

– Recommendation: Conditional recommendation for eligible patients with obesity (aligns with metabolic indications).

Weight loss — lifestyle → cancer

– Evidence statement: WHI observational data — intentional ≥5% loss associated with lower obesity-associated (HR 0.88) and endometrial (HR 0.61) cancer; Look AHEAD RCT showed no significant difference (HR 0.84; modest weight difference limited power). >10% loss may be needed.[2]

– Certainty: Low (RCT null but underpowered; observational positive).

– Recommendation: Conditional recommendation (benefits for cardiometabolic health independent of cancer).

HPV vaccination → cervical and HPV-related cancer

– Evidence statement: Moderate-certainty Cochrane evidence that HPV vaccination reduces invasive cervical cancer (RR 0.37) and CIN3+ (RR 0.39), with greatest benefit vaccinating before sexual debut. Swedish and English population studies confirm reduced invasive cancer (up to 88% if vaccinated <17 yrs).[20][21][22]

– Certainty: High (for CIN precancer, from RCTs); Moderate (for invasive cervical cancer).[23]

– Recommendation: Strong recommendation within licensed/national programme indications.

Aspirin → colorectal and overall cancer (general population)

– Evidence statement: Conflicting by age and follow-up duration. USPSTF/Rothwell analyses suggest ~40% CRC incidence reduction and reduced CRC mortality emerging ≥10–20 years after initiation; Cochrane 2026 found little/no CRC difference before 15 years and very-low-certainty benefit thereafter. ASPREE (initiation ≥70 yrs) showed no incidence benefit and a 15% increase in cancer mortality (excess metastatic/stage 4 disease). High-certainty evidence of increased serious extracranial haemorrhage (RR 1.59).[24][25][26][1]

– Certainty: Moderate (CRC incidence, long-latency); Low/Very low (overall cancer, mortality; age-dependent harm).

– Recommendation: Conditional recommendation only for younger average-risk adults (~50–65 yrs) with long life expectancy where CVD/bleeding risk is balanced; Recommend against initiation for cancer prevention in adults ≥70 years.[1][27]

Aspirin → colorectal cancer in Lynch syndrome

– Evidence statement: CAPP2 RCT — 600 mg daily ≥2 years reduced incident CRC (ITT HR 0.65; per-protocol HR 0.56) with no significant excess adverse events; NNT 24.[28]

– Certainty: Moderate (single RCT, wide CI, but prospective randomised).

– Recommendation: Strong recommendation (NCCN category 2A) to consider daily aspirin in Lynch syndrome; optimal dose under study (CAPP3).[29]

Metformin → cancer incidence

– Evidence statement: Observational meta-analyses suggest ~10–40% lower incidence, but heavily confounded (time-related biases, publication bias, Egger p<0.001). RCT-level data and trial sequential analysis exclude a clinically significant overall effect; DPP 21-year follow-up: no reduction (HR 0.90, NS).[30][2][3][31]

– Certainty: Low (observational positive contradicted by RCT/near-RCT null).

– Recommendation: Only in research for cancer prevention as a sole indication; reasonable adjunct where already indicated for dysglycaemia.

GLP-1 receptor agonists → obesity-associated cancer

– Evidence statement: Large cohorts/target-trial emulations show lower obesity-associated cancer vs insulin/other agents (e.g. HR 0.83 overall; site-specific HRs 0.41–0.76). However, a 2025 RCT meta-analysis (48 trials, n=94,245) found GLP-1RAs probably have little/no effect on obesity-related cancers (short follow-up, not designed for cancer). Signal of possible increased kidney cancer in some cohorts.[2][32][33][34][35]

– Certainty: Low (observational benefit vs moderate-certainty RCT null; short follow-up).

– Recommendation: Conditional recommendation where licensed for obesity/diabetes; not recommended as a standalone cancer-prevention agent.

Vitamin D → cancer incidence and mortality

– Evidence statement: RCT meta-analyses consistently show no reduction in total cancer incidence (RR ~0.98–1.00). A significant reduction in cancer mortality is seen with daily (not bolus) dosing (RR ~0.88); VITAL secondary analysis showed reduced advanced/metastatic cancer (HR 0.83), stronger in normal-weight individuals. Endocrine Society and USPSTF do not recommend supplementation for cancer prevention in replete adults.[36][37][38][39][40]

– Certainty: High (no incidence benefit); Moderate (mortality benefit, daily dosing).

– Recommendation: Recommend against supplementation to reduce cancer incidence; Conditional — correct deficiency (<20 ng/mL / 50 nmol/L) with standard daily dosing; avoid high-dose bolus regimens.

Mediterranean diet / limiting red and processed meat → cancer

– Evidence statement: Moderate-certainty meta-analyses associate high Mediterranean-diet adherence with modestly lower risk of several site-specific cancers (colorectal HR ~0.84) and cancer mortality (RR ~0.97). Processed meat is a Group 1 and red meat a Group 2A carcinogen for colorectal cancer.[41][42][43][44]

– Certainty: Moderate (large cohorts, two supportive RCTs; residual confounding).

– Recommendation: Strong recommendation for a predominantly plant-based/Mediterranean pattern with minimal processed meat.

Rapamycin/rapalogs and senolytics → cancer

– Evidence statement: Robust murine cancer-delay data and human biomarker/geroscience signals only; no human trials with cancer incidence endpoints.[4][8][10]

– Certainty: Very low (preclinical/mechanistic; human surrogate biomarkers).

– Recommendation: Only in research — do not offer for cancer prevention outside clinical trials.



4. Patient selection and indications

Who may benefit (whole-population priorities, all patients):

– Any current smoker → cessation support (highest yield).[46][12]

– Any regular alcohol consumer → reduction/cessation counselling.[6][14]

– Overweight/obese adults (BMI ≥25–30) → weight management, physical activity.[2]

– Physically inactive adults → structured activity prescription.[17]

– Age-eligible/unvaccinated for HPV → vaccination per national schedule.[20]

Targeted chemoprevention candidates:

– Lynch syndrome / confirmed MMR pathogenic variant → aspirin (strongest chemoprevention indication).[29][28]

– Younger average-risk adults (~50–65 yrs) with balanced CVD/bleeding profile and ≥10-year life expectancy → aspirin may be considered.[24]

– Higher CRC risk (family history, prior adenomas) → aspirin discussion.[24]

Exclusion / high-risk groups (avoid or specialist input):

– Aspirin: age ≥70 for de novo cancer prevention; active peptic ulcer/GI bleeding, bleeding diathesis, uncontrolled hypertension, concurrent anticoagulation, untreated H. pylori, pregnancy (Category D at high dose).[1][47]

– High-dose/bolus vitamin D: avoid supraphysiological regimens (hypercalcaemia; signal of higher mortality with high doses).[48][37]

– GLP-1RA/metformin: use only within licensed metabolic indications; caution re. kidney cancer signal and unproven cancer benefit.[35]

Regulatory/ethical status:

– On-label / guideline-based: smoking cessation, alcohol reduction, physical activity, HPV vaccination, bariatric surgery (metabolic indications), vitamin D repletion for deficiency, aspirin in Lynch syndrome (NCCN 2A).

– Off-label for cancer prevention: aspirin in general population (population-dependent; USPSTF-informed), metformin, GLP-1RAs, high-dose vitamin D.

– Only in research: rapamycin/rapalogs, senolytics, metformin as a standalone anti-cancer agent (e.g. within trials/registries).



5. Assessment and baseline work-up

History and examination:

– Personal and 3-generation family cancer history; flag features suggesting hereditary syndromes → refer to NHS clinical genetics (do not initiate germline testing casually).

– Tobacco (pack-years), alcohol (units/week; AUDIT-C), diet, physical activity level, current medications (anticoagulants/antiplatelets, hormone therapy).

– Anthropometrics: BMI, waist circumference/waist-to-hip ratio.

– Confirm up-to-date participation in NHS screening (bowel, breast, cervical) and eligibility for targeted lung health check.

Baseline investigations (tailored):

– FBC, U&E, LFTs, HbA1c, lipids; 25-hydroxyvitamin D if deficiency suspected.

– H. pylori testing/eradication before aspirin if risk factors.

– Bleeding-risk assessment before aspirin.

– Genetics: confirmed pathogenic MMR variant documentation before Lynch chemoprevention.

Risk stratification:

– CVD/bleeding balance for aspirin (e.g. QRISK3 for CVD; individual bleeding factors — age, prior GI bleed, NSAID/anticoagulant use).

– Cancer risk tier: average vs elevated (family history, obesity, hereditary syndrome).

Baseline documentation for follow-up: weight/BMI/waist, smoking and alcohol status, activity level, screening status, medication indications and consent for any off-label use. Ageing “biomarkers” (e.g. epigenetic clocks, senescence markers) are research tools only and should not be used to infer cancer benefit or guide therapy.[8]



6. Dosing regimens and practical implementation

Robust human data:

– Physical activity: ≥150–300 min/week moderate or 75–150 min vigorous, plus ≥2 sessions/week muscle-strengthening (WHO). Dose-response with no clear lower threshold; even brief vigorous intermittent bursts (VILPA, ~4.5 min/day) associate with lower cancer incidence. Sun-safe practice when outdoors (melanoma caveat).[49][50]

– Alcohol: lowest achievable; frame no safe level for cancer.[6]

– HPV vaccine: 9-valent per UK schedule (routine adolescent programme; catch-up per eligibility). Two doses if <15 years, three doses if older/immunocompromised.

– Aspirin in Lynch syndrome: CAPP2 used 600 mg/day ≥2 years; lower doses (e.g. 75–150 mg) are widely used pragmatically given comparable efficacy signals and lower bleeding, pending CAPP3 dose data — discuss individualised dose.[28][47]

– Aspirin, general population (if offered): 75–100 mg daily; benefit requires ≥5–10 years and long latency for CRC; no added benefit above 325 mg.[5]

– Vitamin D (deficiency correction only): daily 400–2000 IU targeting repletion; avoid infrequent large boluses.[48]

– Bariatric/metabolic surgery: standard sleeve gastrectomy or Roux-en-Y via NHS/accredited pathways; cancer benefit correlates with magnitude/durability of weight loss (>20%).[19]

Extrapolated / early-phase — use with caution or research only:

– Metformin: typical dose 500 mg titrated to 850 mg–1 g twice daily where indicated for dysglycaemia; no validated anti-cancer dosing.[31]

– GLP-1RAs: licensed obesity/diabetes dosing only; no cancer-prevention regimen established.[34]

– Rapamycin / rapalogs, senolytics (D+Q, fisetin): no validated human anti-cancer dose or schedule; confine to trials.[8]



7. Monitoring, safety and follow-up

Monitoring plan:

– Behavioural interventions: review smoking/alcohol status, weight/waist, activity at 3–6 monthly intervals initially, then annually.

– Aspirin: monitor for GI symptoms/bleeding; check for new anticoagulant/NSAID use; reassess bleeding risk annually and with ageing.

– Vitamin D: recheck 25(OH)D and calcium if high-dose or symptomatic; avoid over-supplementation.

– Metformin/GLP-1RA: standard metabolic monitoring (renal function, GI tolerance); no cancer-specific surveillance justified for prevention.

– Ensure ongoing engagement with NHS organised screening — chemoprevention does not replace screening or colonoscopic surveillance (essential in Lynch syndrome).[29]

Suggested intervals: short-term (0–3 months) tolerability/adherence; medium-term (6–12 months) efficacy of behaviour change and metabolic parameters; long-term (annual) risk reassessment and screening alignment.

Adverse effects:

– Aspirin: serious extracranial haemorrhage (RR 1.59; high certainty), hemorrhagic stroke (Peto OR ~1.40) — risk rises with age; in ≥70s, associated with excess metastatic cancer and cancer mortality. Action: stop for significant bleeding, dyspepsia unresponsive to management, or age-related risk tipping.[26][1]

– Vitamin D (high-dose): hypercalcaemia, nephrolithiasis; possible higher mortality at high doses. Action: reduce/stop, check calcium.[37][48]

– GLP-1RAs: GI intolerance; monitor kidney cancer signal (uncertain).[35]

– Bariatric surgery: perioperative and nutritional risks per surgical pathway.

Interactions/comorbidity: aspirin + anticoagulants/other antiplatelets/NSAIDs/SSRIs → additive bleeding; confirm H. pylori eradication. Metformin — renal dosing/withhold in acute illness.

Special populations:

– Pregnancy/breastfeeding: aspirin Category D at high dose — avoid high-dose in women of childbearing potential not using contraception; low-dose 81 mg considered acceptable in pregnancy but not for cancer prevention. GLP-1RAs contraindicated in pregnancy.[47]

– Renal/hepatic impairment: adjust/avoid metformin; caution with aspirin.

– Frailty / extremes of age: avoid initiating aspirin chemoprevention ≥70 years; prioritise activity, nutrition, deprescribing over new agents.[1]



8. Contraindications and cautions

Absolute contraindications:

– Aspirin: active GI bleeding/peptic ulcer, aspirin hypersensitivity, severe bleeding disorder.

– High-dose vitamin D: hypercalcaemia.

– GLP-1RA: personal/family history of medullary thyroid carcinoma or MEN2 (per label); pregnancy.

Relative contraindications / specialist advice:

– Aspirin: age ≥70 (de novo prevention), concurrent anticoagulation, uncontrolled hypertension, prior GI bleed, untreated H. pylori.[1][47]

– Any off-label chemoprevention in patients with limited life expectancy or high polypharmacy burden.

Harm likely to outweigh benefit (current evidence):

– Aspirin initiated for cancer prevention in adults ≥70 years.[1][27]

– High-dose/bolus vitamin D in replete adults.[37]

– Rapamycin/rapalogs or senolytics for cancer prevention outside trials (no human efficacy data; real toxicity).[8]



9. Practical management scenarios

Scenario A — Middle-aged adult (55 yrs) with multiple cardiometabolic risk factors (obesity, prediabetes, hypertension, ex-smoker)

– Overall: Offer intensive lifestyle intervention (Strong); Consider aspirin only if CVD/bleeding balance favourable (Conditional).

– Assessment: BMI/waist, HbA1c, lipids, QRISK3, bleeding risk, screening status.

– Shared decision-making: prioritise smoking abstinence maintenance, alcohol minimisation, ≥150 min/week activity, Mediterranean pattern, ≥10% weight loss target.[17][2][41]

– Initiation: structured weight-management ± licensed pharmacotherapy/GLP-1RA for obesity (metabolic indication, not cancer claim); consider low-dose aspirin (75–100 mg) if net CVD benefit and low bleeding risk, with explicit counselling that cancer benefit is long-latency and uncertain.[24]

– Monitoring: 3–6 monthly weight/metabolic review; annual bleeding-risk reassessment.

– Escalate/stop: refer for bariatric assessment if BMI ≥35 with comorbidity and lifestyle failure; stop aspirin if bleeding or age/risk shift.[51]

Scenario B — Older, frail patient (78 yrs) with multimorbidity

– Overall: Avoid initiating aspirin/off-label chemoprevention (Recommend against); Offer activity, nutrition, deprescribing (Conditional/Strong).

– Assessment: frailty, falls/bleeding risk, life expectancy, current screening appropriateness.

– Shared decision-making: emphasise function, resistance/aerobic activity as tolerated, adequate protein, correction of vitamin D deficiency only.

– Initiation: no new aspirin for cancer prevention (ASPREE: no benefit, excess cancer mortality).[1]

– Monitoring: annual medication review; align/deprescribe screening to life expectancy.

– Escalate/stop: reassess any inherited aspirin use.

Scenario C — Confirmed Lynch syndrome, under NHS genetics/gastroenterology

– Overall: Offer daily aspirin chemoprevention (Strong; NCCN 2A) as an adjunct to colonoscopic surveillance.[29][28]

– Assessment: confirm MMR variant, bleeding risk, H. pylori status, childbearing plans.

– Shared decision-making: NNT 24 for CRC; discuss 600 mg (CAPP2 evidence) vs pragmatic lower dose; aspirin is Category D — contraception counselling in women of childbearing potential.[47]

– Initiation: aspirin after H. pylori addressed; document consent and dose rationale.

– Monitoring: continue gene-specific colonoscopy surveillance (do not substitute); annual bleeding review.

– Escalate/stop: stop for significant bleeding/pregnancy; coordinate all decisions with the genetics/GI team.



10. Research gaps and future directions

– Aspirin: optimal dose (CAPP3), age at initiation, and duration; mechanism of increased late-stage cancer in older adults.[1][28]

– Metformin: whether any site-specific (e.g. colorectal, hepatocellular) benefit survives bias-controlled RCTs in non-diabetic populations.[3][31]

– GLP-1RAs: long-term, adequately powered RCTs with cancer endpoints; resolution of the kidney-cancer signal; whether benefit is weight-mediated or direct.[34][35]

– Vitamin D: confirmation of the daily-dosing cancer-mortality signal and identification of responsive subgroups (normal-weight, deficient).[38][39]

– Weight loss: head-to-head durability of surgical vs GLP-1RA-induced loss for cancer outcomes.[2]

– Geroscience agents: no human cancer-incidence data for rapamycin/rapalogs or senolytics — first-in-human prevention trials and validated ageing-biomarker surrogates are required before clinical use.[8][10]

Practice statement: Outside licensed/guideline indications, chemoprevention and all geroscience agents should be delivered within well-designed clinical trials or prospective registries, with hard clinical endpoints rather than surrogate ageing biomarkers.

 

References

1. Cancer Incidence and Mortality With Aspirin in Older Adults. Orchard SG, Polekhina G, Zalcberg J, et al. JAMA Oncology. 2026;:2844193. doi:10.1001/jamaoncol.2025.6196.
2. Obesity and Cancer. Shen S, Brown KA, Green AK, Iyengar NM. JAMA. 2026;:2846256. doi:10.1001/jama.2026.1114.
3. Metformin beyond type 2 diabetes: Emerging and potential new indications. Petrie JR. Diabetes, Obesity & Metabolism. 2024;26 Suppl 3:31-41. doi:10.1111/dom.15756.
4. Cancer Prevention With Rapamycin. Blagosklonny MV. Oncotarget. 2023;14:342-350. doi:10.18632/oncotarget.28410.
5. Preventive Therapy for Cancer. Cuzick J. The Lancet. Oncology. 2017;18(8):e472-e482. doi:10.1016/S1470-2045(17)30536-3.
6. The IARC Perspective on Alcohol Reduction or Cessation and Cancer Risk. Gapstur SM, Bouvard V, Nethan ST, et al. The New England Journal of Medicine. 2023;389(26):2486-2494. doi:10.1056/NEJMsr2306723.
7. Alcohol‐Attributable Cancer: Update From the Global Burden of Disease 2021 Study. Danpanichkul P, Pang Y, Díaz LA, et al. Alimentary Pharmacology & Therapeutics. 2025;62(1):33-47. doi:10.1111/apt.70163.
8. Geroscience. Kritchevsky SB, Cummings SR. JAMA. 2025;334(12):1094-1102. doi:10.1001/jama.2025.11289.
9. Senescence, Aging and Disease Throughout the Gastrointestinal System. Ferreira-Gonzalez S, Matsumoto T, Hara E, Forbes SJ. Gastroenterology. 2025;169(7):1357-1379. doi:10.1053/j.gastro.2025.06.010.
10. Rapamycin Exerts Its Geroprotective Effects in the Ageing Human Immune System by Enhancing Resilience Against DNA Damage. Kell L, Jones EJ, Gharahdaghi N, et al. Aging Cell. 2026;25(2):e70364. doi:10.1111/acel.70364.
11. Effect of Smoking Reduction, Cessation, and Resumption on Cancer Risk: A Nationwide Cohort Study. Yoo JE, Han K, Shin DW, et al. Cancer. 2022;128(11):2126-2137. doi:10.1002/cncr.34172.
12. Cancer Risk Following Smoking Cessation in Korea. Park E, Kang HY, Lim MK, Kim B, Oh JK. JAMA Network Open. 2024;7(2):e2354958. doi:10.1001/jamanetworkopen.2023.54958.
13. Smoking and Smoking Cessation in Relation to Mortality in Women. Kenfield SA, Stampfer MJ, Rosner BA, Colditz GA. JAMA. 2008;299(17):2037-47. doi:10.1001/jama.299.17.2037.
14. The IARC Perspective on the Effects of Policies on Reducing Alcohol Consumption. Gapstur SM, Mariosa D, Neamtiu L, et al. The New England Journal of Medicine. 2025;392(17):1752-1759. doi:10.1056/NEJMsr2413289.
15. Association Between Changes in Alcohol Consumption and Cancer Risk. Yoo JE, Han K, Shin DW, et al. JAMA Network Open. 2022;5(8):e2228544. doi:10.1001/jamanetworkopen.2022.28544.
16. Alcohol and Cancer Risk. Morford KL, Tetrault JM, O’Connor PG. JAMA. 2025;:2837352. doi:10.1001/jama.2025.11229.
17. Physical Activity in Cancer Prevention and Survival: A Systematic Review. McTiernan A, Friedenreich CM, Katzmarzyk PT, et al. Medicine and Science in Sports and Exercise. 2019;51(6):1252-1261. doi:10.1249/MSS.0000000000001937.
18. Physical Activity and Cancer Risk: A Dose-Response Analysis for the Global Burden of Disease Study 2019. Diao X, Ling Y, Zeng Y, et al. Cancer Communications (London, England). 2023;43(11):1229-1243. doi:10.1002/cac2.12488.
19. Association of Bariatric Surgery With Cancer Risk and Mortality in Adults With Obesity. Aminian A, Wilson R, Al-Kurd A, et al. JAMA. 2022;327(24):2423-2433. doi:10.1001/jama.2022.9009.
20. Effects of Human Papillomavirus (HPV) Vaccination Programmes on Community Rates of HPV-related Disease and Harms From Vaccination. Henschke N, Bergman H, Buckley BS, et al. The Cochrane Database of Systematic Reviews. 2025;11:CD015363. doi:10.1002/14651858.CD015363.pub2.
21. HPV Vaccination and the Risk of Invasive Cervical Cancer. Lei J, Ploner A, Elfström KM, et al. The New England Journal of Medicine. 2020;383(14):1340-1348. doi:10.1056/NEJMoa1917338.
22. The Effects of the National HPV Vaccination Programme in England, UK, on Cervical Cancer and Grade 3 Cervical Intraepithelial Neoplasia Incidence: A Register-Based Observational Study. Falcaro M, Castañon A, Ndlela B, et al. Lancet (London, England). 2021;398(10316):2084-2092. doi:10.1016/S0140-6736(21)02178-4.
23. Prophylactic Vaccination Against Human Papillomaviruses to Prevent Cervical Cancer and Its Precursors. Arbyn M, Xu L, Simoens C, Martin-Hirsch PP. The Cochrane Database of Systematic Reviews. 2018;5:CD009069. doi:10.1002/14651858.CD009069.pub3.
24. Aspirin for Primary Prevention of Atherosclerotic Cardiovascular Disease. Mora S, Manson JE. JAMA Internal Medicine. 2016;176(8):1195-204. doi:10.1001/jamainternmed.2016.2648.
25. Aspirin for the Prevention of Cancer Incidence and Mortality: Systematic Evidence Reviews for the U.S. Preventive Services Task Force. Chubak J, Whitlock EP, Williams SB, et al. Annals of Internal Medicine. 2016;164(12):814-25. doi:10.7326/M15-2117.
26. Aspirin and Other Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) for Preventing Colorectal Cancer and Colorectal Adenoma in the General Population. Cai Z, Meng Y, Yang W, et al. The Cochrane Database of Systematic Reviews. 2026;4:CD015266. doi:10.1002/14651858.CD015266.pub3.
27. Aspirin vs Placebo as Adjuvant Therapy for Breast Cancer. Chen WY, Ballman KV, Partridge AH, et al. JAMA. 2024;331(20):1714-1721. doi:10.1001/jama.2024.4840.
28. Cancer Prevention With Aspirin in Hereditary Colorectal Cancer (Lynch Syndrome), 10-Year Follow-Up and Registry-Based 20-Year Data in the CAPP2 Study: A Double-Blind, Randomised, Placebo-Controlled Trial. Burn J, Sheth H, Elliott F, et al. Lancet (London, England). 2020;395(10240):1855-1863. doi:10.1016/S0140-6736(20)30366-4.
29. Genetic/Familial High-Risk Assessment: Colorectal, Endometrial, Esophageal, and Gastric. National Comprehensive Cancer Network. Updated 2026-06-16.
30. Association of Metformin Use and Cancer Incidence: A Systematic Review and Meta-Analysis. O’Connor L, Bailey-Whyte M, Bhattacharya M, et al. Journal of the National Cancer Institute. 2024;116(4):518-529. doi:10.1093/jnci/djae021.
31. Randomized Study of Metformin and Intensive Lifestyle Intervention on Cancer Incidence Over 21 Years of Follow-Up in the Diabetes Prevention Program. Heckman-Stoddard BM, Crandall JP, Edelstein SL, et al. Cancer Prevention Research (Philadelphia, Pa.). 2025;18(7):401-411. doi:10.1158/1940-6207.CAPR-23-0461.
32. Glucagon-Like Peptide 1 Receptor Agonists and 13 Obesity-Associated Cancers in Patients With Type 2 Diabetes. Wang L, Xu R, Kaelber DC, Berger NA. JAMA Network Open. 2024;7(7):e2421305. doi:10.1001/jamanetworkopen.2024.21305.
33. GLP-1 Receptor Agonist Use and Cancer Risk in Obese Nondiabetic Adults. Hsu AH, Ramirez PT, Chang YH, et al. Annals of Oncology : Official Journal of the European Society for Medical Oncology. 2026;37(8):1178-1185. doi:10.1016/j.annonc.2026.04.013.
34. Risk for Cancer With Glucagon-Like Peptide-1 Receptor Agonists and Dual Agonists : A Systematic Review and Meta-Analysis. Ko A, Chang YC, Bahar F, et al. Annals of Internal Medicine. 2025;. doi:10.7326/ANNALS-25-02237.
35. GLP-1 Receptor Agonists and Cancer Risk in Adults With Obesity. Dai H, Li Y, Lee YA, et al. JAMA Oncology. 2025;11(10):1186-1193. doi:10.1001/jamaoncol.2025.2681.
36. Vitamin D Supplementation and Total Cancer Incidence and Mortality: A Meta-Analysis of Randomized Controlled Trials. Keum N, Lee DH, Greenwood DC, Manson JE, Giovannucci E. Annals of Oncology : Official Journal of the European Society for Medical Oncology. 2019;30(5):733-743. doi:10.1093/annonc/mdz059.
37. Vitamin D for the Prevention of Disease: An Endocrine Society Clinical Practice Guideline. Demay MB, Pittas AG, Bikle DD, et al. The Journal of Clinical Endocrinology and Metabolism. 2024;109(8):1907-1947. doi:10.1210/clinem/dgae290.
38. Efficacy of Vitamin D3 Supplementation on Cancer Mortality: Systematic Review and Individual Patient Data Meta-Analysis of Randomised Controlled Trials. Kuznia S, Zhu A, Akutsu T, et al. Ageing Research Reviews. 2023;87:101923. doi:10.1016/j.arr.2023.101923.
39. Effect of Vitamin D3 Supplements on Development of Advanced Cancer: A Secondary Analysis of the VITAL Randomized Clinical Trial. Chandler PD, Chen WY, Ajala ON, et al. JAMA Network Open. 2020;3(11):e2025850. doi:10.1001/jamanetworkopen.2020.25850.
40. Vitamin, Mineral, and Multivitamin Supplementation to Prevent Cardiovascular Disease and Cancer: US Preventive Services Task Force Recommendation Statement. US Preventive Services Task Force, Mangione CM, Barry MJ, et al. JAMA. 2022;327(23):2326-2333. doi:10.1001/jama.2022.8970.
41. Efficacy of Mediterranean Diet for the Primary Prevention of Oncological Diseases: A Systematic Review and Meta-Analysis Featured in the Italian National Guidelines “La Dieta Mediterranea”. Brunello A, Nucci D, Veronese N, et al. Nutrition (Burbank, Los Angeles County, Calif.). 2026;148:113131. doi:10.1016/j.nut.2026.113131.
42. Adherence to the Mediterranean Diet and Its Protective Effects Against Colorectal Cancer: A Meta-Analysis of 26 Studies With 2,217,404 Participants. Ungvari Z, Fekete M, Fekete JT, et al. GeroScience. 2025;47(1):1105-1121. doi:10.1007/s11357-024-01296-9.
43. An Updated Systematic Review and Meta-Analysis on Adherence to Mediterranean Diet and Risk of Cancer. Morze J, Danielewicz A, Przybyłowicz K, et al. European Journal of Nutrition. 2021;60(3):1561-1586. doi:10.1007/s00394-020-02346-6.
44. American Cancer Society Guideline for Diet and Physical Activity for Cancer Prevention. Rock CL, Thomson C, Gansler T, et al. CA: A Cancer Journal for Clinicians. 2020;70(4):245-271. doi:10.3322/caac.21591.
45. American Cancer Society Guideline for Diet and Physical Activity for Cancer Prevention. Rock CL, Thomson C, Gansler T, et al. CA: A Cancer Journal for Clinicians. 2020;70(4):245-271. doi:10.3322/caac.21591.
46. Smoking Cessation. National Comprehensive Cancer Network. Updated 2026-04-06.
47. Review article: Lynch Syndrome—a mechanistic and clinical management update. Curtius K, Gupta S, Boland CR. Alimentary Pharmacology & Therapeutics. 2022;55(8):960-977. doi:10.1111/apt.16826.
48. Endocrine Health in Survivors of Adult-Onset Cancer. Link-Rachner CS, Göbel A, Jaschke NP, Rachner TD. The Lancet. Diabetes & Endocrinology. 2024;12(5):350-364. doi:10.1016/S2213-8587(24)00088-3.
49. Vigorous Intermittent Lifestyle Physical Activity and Cancer Incidence Among Nonexercising Adults: The UK Biobank Accelerometry Study. Stamatakis E, Ahmadi MN, Friedenreich CM, et al. JAMA Oncology. 2023;9(9):1255-1259. doi:10.1001/jamaoncol.2023.1830.
50. American College of Sports Medicine Roundtable Report on Physical Activity, Sedentary Behavior, and Cancer Prevention and Control. Patel AV, Friedenreich CM, Moore SC, et al. Medicine and Science in Sports and Exercise. 2019;51(11):2391-2402. doi:10.1249/MSS.0000000000002117.
51. 2022 American Society for Metabolic and Bariatric Surgery (ASMBS) and International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO): Indications for Metabolic and Bariatric Surgery. Eisenberg D, Shikora SA, Aarts E, et al. Surgery for Obesity and Related Diseases : Official Journal of the American Society for Bariatric Surgery. 2022;18(12):1345-1356. doi:10.1016/j.soard.2022.08.013.