What causes cancer?

What Causes Cancer

Cancer is fundamentally caused by accumulated genetic and epigenetic changes in cells, but the overwhelming majority (80-95%) of cancer cases result from modifiable environmental and lifestyle factors rather than inherited genetic defects. 1, 2

Primary Causative Factors

Tobacco Use - The Single Most Important Cause

• Tobacco use is the single most significant cause of cancer, responsible for approximately 25-30% of all cancer deaths. 3, 4, 1
• Cigarette smoking causes more than 80% of lung cancers and is causally linked to at least 12 cancer types with convincing evidence. 3
• There is a clear dose-response relationship: cancer risk increases with number of cigarettes smoked, depth of inhalation, and duration of smoking. 3, 5
• Smoking is causally related to cancers of the lung, oral cavity, pharynx, larynx, esophagus, bladder, kidney, pancreas, colon, stomach, cervix, and causes leukemia. 3, 5

Diet and Nutrition

• Diet accounts for 30-35% of all cancer-related deaths, making it nearly as important as tobacco. 1
• Diets low in fruits and vegetables increase cancer risk across multiple sites. 4, 1
• High consumption of red and processed meat is associated with increased colorectal and pancreatic cancer risk. 3
• Fried foods contribute to cancer development through inflammatory pathways. 1

Obesity and Physical Inactivity

• Obesity is an established risk factor with convincing evidence for renal cell cancer, endometrial cancer, and breast cancer (postmenopausal). 3
• Physical inactivity contributes significantly to cancer risk, particularly for colon cancer. 3, 4
• The combination of obesity and sedentary lifestyle accounts for a substantial portion of preventable cancers. 3, 1

Alcohol Consumption

• Excessive alcohol consumption is responsible for approximately 15-20% of cancer cases. 4, 1
• Alcohol increases risk for oral cavity, pharyngeal, esophageal, liver, colorectal, and breast cancers. 3
• Up to 75% of oral cancer cases in the United States are attributable to the combined effects of tobacco and alcohol use. 5

Infectious Agents

• Infections account for approximately 15-20% of cancer cases globally. 1, 2
• Key carcinogenic infections include HPV (cervical cancer), hepatitis B and C (liver cancer), H. pylori (gastric cancer), and HIV (various cancers). 3

Occupational and Environmental Exposures

• Occupational carcinogens include asbestos, nickel, chromium, arsenic, and radiation exposure. 3
• Indoor and outdoor air pollution contribute to lung cancer risk. 3
• Radon gas exposure accounts for 10-14% of lung cancer cases. 3
• Environmental pollutants and carcinogenic chemicals in the environment cause 80-90% of malignant tumors. 2

Radiation Exposure

• Sun exposure (UV radiation) is a major cause of skin cancers including melanoma. 4, 1
• Ionizing radiation from various sources increases cancer risk across multiple sites. 3

Genetic vs. Environmental Contribution

Only 5-10% of all cancer cases can be attributed to inherited genetic defects; the remaining 90-95% have roots in environment and lifestyle. 1

• While genetic inheritance influences cancer risk and cancer arises from genetic mutations in cells, most variation in cancer risk across populations results from non-inherited factors. 3
• Family history serves as a useful risk indicator but represents a small fraction of overall cancer burden. 3
• Approximately 20% of ovarian cancers and 10% of breast cancers are hereditary, but these are exceptions rather than the rule. 3

Mechanistic Understanding

Cellular Level Changes

• Cancer develops through accumulation of chromosomal and molecular aberrations leading to genetic instability. 2, 6
• Carcinogens and tumor promoters act through various molecular mechanisms, with repeated exposure to multiple agents typically necessary. 6
• Inflammation is the critical link between cancer-causing agents and cancer development. 1

Multi-Step Process

• Cancer development requires multiple genetic and epigenetic steps over time. 2, 6
• The interaction of various risk factors has the largest contribution to cancer development. 2

Clinical Implications for Prevention

The evidence is unequivocal: cancer is largely a preventable disease requiring major lifestyle modifications. 1

Primary Prevention Priorities

1. Smoking cessation and tobacco avoidance - eliminates the single largest cancer risk factor 3, 5, 4
2. Maintain healthy weight through diet and exercise - addresses 30-35% of cancer deaths 3, 1
3. Consume 5+ servings of fruits and vegetables daily - reduces risk across multiple cancer sites 3
4. Limit alcohol to ≤1 drink per day - particularly important for breast and oral cancers 3, 5
5. Engage in regular vigorous physical activity (≥4 hours/week) - especially protective against colon and breast cancer 3
6. Minimize red and processed meat consumption - reduces colorectal cancer risk 3
7. Avoid excessive sun exposure - prevents skin cancers 4, 1

Common Pitfall

The most critical error is underestimating the preventability of cancer. A very large proportion of cancer's impact could be ameliorated if people avoided modifiable exposures, yet these factors remain inadequately addressed in clinical practice. 4