# Cancer Prevention Beyond Screening: Lifestyle and Chemoprevention

## Overview

Cancer is the second leading cause of death in the U.S. (~600,000 deaths/year) and first in adults under 85. An estimated 40-50% of cancers are attributable to modifiable risk factors. Primary prevention (reducing incidence) is distinct from secondary prevention (screening/early detection) Key modifiable risk factors: tobacco, obesity, physical inactivity, diet, alcohol, ultraviolet radiation, infections (HPV, HBV, H. pylori) Chemoprevention refers to pharmacologic agents taken to reduce cancer risk in high-risk individuals. The preventive medicine physician integrates population-level risk reduction with clinical chemoprevention counseling.

## Lifestyle Factors in Cancer Prevention

### Tobacco

Responsible for ~30% of all cancer deaths. Causally linked to cancers of the lung, head/neck, esophagus, stomach, pancreas, kidney, bladder, cervix, colon, and acute myeloid leukemia. Cessation at any age reduces cancer risk; 10 years after quitting, lung cancer risk drops by ~50%. Secondhand smoke exposure causes ~7,000 lung cancer deaths/year in U.S. non-smokers.

### Obesity and Body Fatness

IARC classifies excess body fatness as a cause of >=13 cancers: breast (postmenopausal), colorectal, endometrial, esophageal adenocarcinoma, kidney, liver, gallbladder, pancreas, stomach cardia, ovarian, thyroid, meningioma, multiple myeloma. Mechanisms: chronic inflammation, insulin/IGF-1 signaling, sex hormone dysregulation, adipokine effects. Population-attributable fraction: obesity accounts for ~8% of all cancers in the U.S. Weight loss (particularly sustained >=5%) reduces cancer risk -- bariatric surgery studies show 33% reduction in cancer incidence.

### Physical Activity

Regular physical activity reduces risk of colon cancer (~20-25%), breast cancer (~20-25%), endometrial cancer (~20%), and possibly lung, liver, and stomach cancers. Mechanisms: reduced insulin/IGF-1, anti-inflammatory effects, improved immune function, reduced sex hormones. Dose-response: greater activity = greater risk reduction; benefit seen at recommended levels (150 min/week moderate-intensity) Sedentary behavior independently associated with increased cancer risk.

### Diet

**Processed meat** (IARC Group 1 carcinogen): ~18% increased colorectal cancer risk per 50 g/day. **Red meat** (IARC Group 2A): probable colorectal carcinogen; ~17% increase per 100 g/day. **Fiber**: inverse association with colorectal cancer (~10% risk reduction per 10 g/day) **Fruits and vegetables**: modest inverse association with aerodigestive cancers; overall cancer prevention benefit is weaker than previously thought. **Whole grains**: associated with reduced colorectal cancer risk. **Ultra-processed foods**: emerging association with overall and specific cancer risks. **Dietary patterns**: Mediterranean and DASH-type diets associated with lower overall cancer incidence.

### Alcohol

IARC Group 1 carcinogen; causally linked to cancers of the oral cavity, pharynx, larynx, esophagus, liver, colorectal, and breast. No safe threshold for cancer: even light drinking (1 drink/day) increases breast cancer risk by ~7-10%. Dose-response relationship: risk increases linearly with consumption. Combined alcohol and tobacco use: multiplicative (not merely additive) risk for head/neck and esophageal cancers. Population-attributable fraction: alcohol causes ~5.5% of cancers and 5.8% of cancer deaths worldwide.

### Ultraviolet Radiation

Primary cause of skin cancers (melanoma, basal cell carcinoma, squamous cell carcinoma) Indoor tanning: IARC Group 1 carcinogen; 59% increased melanoma risk with any indoor tanning before age 35. Prevention: sun-protective behaviors, sunscreen (SPF >=30, broad-spectrum), avoidance of tanning beds. USPSTF: counseling for fair-skinned individuals aged 6 months-24 years to minimize UV exposure (B recommendation)

## Infection-Related Cancer Prevention

### HPV Vaccination

HPV causes ~36,000 cancers/year in the U.S.: cervical, oropharyngeal, anal, vulvar, vaginal, penile. 9-valent HPV vaccine (Gardasil 9): prevents ~90% of HPV-related cancers. ACIP recommendation: routine vaccination at ages 11-12; catch-up through age 26; shared clinical decision for ages 27-45. Australia on track for cervical cancer elimination through high-coverage vaccination + screening programs. Impact: 88% reduction in HPV infections in vaccinated age groups in the U.S.

### Hepatitis B Vaccination

Chronic HBV causes hepatocellular carcinoma. Universal infant HBV vaccination (since 1991 in U.S.) has reduced chronic HBV and liver cancer in vaccinated cohorts. ACIP expanded recommendation: universal HBV vaccination for all adults through age 59 (2022)

### H. pylori Eradication

Chronic H. pylori infection causes gastric adenocarcinoma and MALT lymphoma. Eradication reduces gastric cancer risk by ~35-50% in high-risk populations. Mass screening and treatment in high-prevalence populations (East Asia) under investigation. Not currently recommended for routine screening in low-risk U.S. populations.

## Chemoprevention

### Aspirin for Colorectal Cancer

Aspirin reduces colorectal cancer incidence and mortality -- strongest evidence for >=10 years of regular use. USPSTF (2022): insufficient evidence to recommend aspirin for CRC prevention specifically; cardiovascular benefit/risk assessment should drive decision. Previous 2016 recommendation: low-dose aspirin for adults 50-59 with >=10% 10-year CVD risk (included CRC benefit as co-benefit) -- subsequently withdrawn. ACS: does not recommend aspirin solely for cancer prevention. Mechanism: COX-2 inhibition, anti-inflammatory effects, platelet inhibition.

### Tamoxifen and Raloxifene for Breast Cancer

USPSTF (B recommendation): offer risk-reducing medications to women at increased breast cancer risk (>=3% 5-year risk or known BRCA mutation) **Tamoxifen**: reduces invasive breast cancer by ~49% over 5 years (NSABP P-1 trial); can be used pre- or postmenopausal. **Raloxifene**: reduces invasive breast cancer by ~38% (STAR trial); postmenopausal only; fewer side effects than tamoxifen. **Aromatase inhibitors** (exemestane, anastrozole): ~53-65% reduction in breast cancer; postmenopausal women; bone loss and arthralgia. Uptake is very low despite proven efficacy -- <5% of eligible women use chemoprevention. Barriers: fear of side effects (VTE, endometrial cancer with tamoxifen), low awareness, insufficient counseling.

| Agent | Cancer Target | Risk Reduction | Population | Key Side Effects |
|---|---|---|---|---|
| Tamoxifen | Breast | 49% | Pre- and postmenopausal women | VTE, endometrial cancer |
| Raloxifene | Breast | 38% | Postmenopausal women | VTE (fewer than tamoxifen) |
| Exemestane | Breast | 53% | Postmenopausal women | Bone loss, arthralgia |
| Anastrozole | Breast | 53-65% | Postmenopausal women | Bone loss, arthralgia |
| Aspirin | Colorectal | Modest (>=10 yr use) | Adults with CVD risk | GI bleeding |
| Finasteride | Prostate | 25% | Men >=55 | Sexual side effects |

### Finasteride/Dutasteride for Prostate Cancer

PCPT trial: finasteride reduced prostate cancer incidence by 25% but initially raised concern for higher-grade tumors (detection bias likely) REDUCE trial: dutasteride reduced prostate cancer by 23%. Not widely adopted; no USPSTF or ACS recommendation for chemoprevention.

<image>A pie chart or stacked bar showing the attributable fraction of cancer deaths by modifiable risk factor in the U.S.: tobacco (30%), obesity (8%), alcohol (5.5%), physical inactivity (5%), diet (5%), UV radiation (5%), infections (HPV, HBV, H. pylori, ~4%), and other environmental/occupational exposures. The chart emphasizes that collectively, modifiable factors account for roughly 40-50% of cancer incidence. Cancer prevention education illustration.</image>

<image>A comparison table formatted as an infographic showing breast cancer chemoprevention options: tamoxifen (49% risk reduction, pre/postmenopausal, side effects: VTE/endometrial cancer), raloxifene (38% reduction, postmenopausal only, fewer side effects), exemestane (53% reduction, postmenopausal, bone loss/arthralgia), and anastrozole (53% reduction, postmenopausal, bone loss/arthralgia). Eligibility criteria (>=3% 5-year risk by Gail model or BRCA mutation) are noted. Breast cancer chemoprevention education illustration.</image>

<image>A timeline showing the impact of HPV vaccination on HPV-related cancer prevention globally. Milestones include: 2006 FDA approval of quadrivalent HPV vaccine, 2014 9-valent vaccine approval, and projected cervical cancer elimination in high-coverage countries (Australia by ~2035). A graph overlay shows the decline in HPV-type 16/18 prevalence among vaccinated cohorts and the projected reduction in cervical cancer incidence over decades. HPV vaccination and cancer prevention education illustration.</image>

## Clinical Pearls

Even light alcohol consumption (1 drink/day) increases breast cancer risk -- there is no safe level of alcohol for cancer prevention; this contradicts older messaging about "moderate" drinking benefits. HPV vaccination is the most effective cancer prevention vaccine -- universal vaccination at ages 11-12 could prevent ~90% of HPV-related cancers, including oropharyngeal cancers in males. Breast cancer chemoprevention is dramatically underutilized (<5% of eligible women) despite USPSTF B-grade recommendation -- proactive risk assessment and counseling are essential. For boards: know the IARC Group 1 carcinogens (tobacco, alcohol, processed meat, UV, HPV), the breast cancer chemoprevention agents and their risk reductions, and the current status of aspirin for CRC prevention. Obesity is now recognized as a cause of at least 13 cancers -- weight management counseling should frame cancer risk alongside metabolic and cardiovascular risk.

## References

- Islami F, et al. Proportion and number of cancer cases attributable to potentially modifiable risk factors in the U.S. CA Cancer J Clin. 2018;68(1):31-54.
- Fisher B, et al. Tamoxifen for prevention of breast cancer: NSABP P-1 study. J Natl Cancer Inst. 1998;90(18):1371-1388.
- USPSTF. Medications to reduce risk of breast cancer. JAMA. 2019;322(9):857-867.
- Lauby-Secretan B, et al. Body fatness and cancer -- viewpoint of the IARC Working Group. N Engl J Med. 2016;375(8):794-798.
- Lei J, et al. HPV vaccination and the risk of invasive cervical cancer. N Engl J Med. 2020;383(14):1340-1348.