What are the causes of elevated carcinoembryonic antigen (CEA) levels?

Causes of Elevated Carcinoembryonic Antigen (CEA)

Elevated CEA levels occur in both malignant and benign conditions, with the highest levels typically seen in lung fibrosis, pancreatic cancer, uremia, COPD, and colorectal cancer, though numerous non-cancer conditions including gastrointestinal inflammation, liver disease, and even normal aging can cause elevations. 1, 2

Malignant Causes

Gastrointestinal Malignancies

• Colorectal cancer is the classic malignancy associated with CEA elevation, with levels elevated in 71% of patients with gastrointestinal tract carcinomas 1, 3
• Pancreatic cancer ranks among the highest median CEA levels and shows elevation in just over 50% of cases 2, 4
• Gastric malignancies demonstrate CEA elevation in approximately 50% of cases 4
• Cholangiocarcinoma shows CEA elevation in approximately 30% of patients 1

Thoracic Malignancies

• Lung cancer (particularly adenocarcinoma) causes significantly elevated CEA, with 77% of patients with bronchogenic lung cancer having elevated preoperative values 4, 5
• Small cell lung carcinoma shows particularly strong correlation: CEA levels above 10 ng/mL correlate highly with metastatic disease, while values less than 2.5 ng/mL correlate with localized disease 4

Other Malignancies

• Breast cancer shows CEA elevation in 40-73% of patients across stages I-IV, with 80% of patients having CEA elevation 3-10 months prior to clinical symptoms of recurrence 1, 4
• Gynecologic malignancies (cervix, uterus, ovary) produce CEA in 47-75% of cases, correlating with stage and cellular differentiation 4

Prognostic Significance in Cancer

• Preoperative CEA ≥5 ng/mL indicates worse prognosis regardless of tumor stage 1, 6
• Markedly increased levels (>25 ng/mL) are highly suggestive of metastatic cancer, particularly hepatic metastasis 7

Benign Causes

Gastrointestinal Conditions

• Inflammatory bowel disease (Crohn's disease and ulcerative colitis) elevates CEA 1
• Gastritis and peptic ulcer disease affect CEA levels 1, 6
• Diverticulitis can cause elevation 6

Hepatobiliary Conditions

• Liver diseases of various etiologies cause CEA elevation, with 66% of patients with non-neoplastic liver disease showing elevated levels 1, 3
• Benign extrahepatic biliary obstruction elevates CEA, with highest levels occurring when coexistent cholangitis or liver abscess is present 1

Pulmonary Conditions

• Chronic obstructive pulmonary disease (COPD) ranks among the highest median CEA levels 6, 2
• Lung fibrosis shows the highest median CEA levels among all conditions studied 2
• Cigarette smoking alone causes increases in CEA levels, complicating differentiation between benign and malignant conditions 6, 4

Metabolic and Systemic Conditions

• Uremia (chronic kidney disease) shows very high median CEA levels 2
• Diabetes can affect CEA levels 6
• Inflammatory states of various origins elevate CEA 1, 6

Age-Related Elevation

• Normal aging: Healthy individuals older than 65 years have higher median CEA levels, ranking 24th out of 49 conditions studied for median CEA elevation 2

Important Clinical Caveats

Transient Elevations

• CEA levels may be transiently elevated during the first 4-6 weeks of chemotherapy, representing tumor lysis rather than progression, and should be interpreted with caution during this period 1, 8

Diagnostic Limitations

• CEA has high specificity but low sensitivity for colorectal cancer, making it unsuitable for population screening 1, 6
• The CEA test is not recommended for screening to detect early cancer 7

Confirmation Strategy

• Always confirm elevated CEA with retesting before proceeding with extensive workup 1
• Consider the full clinical context, including smoking history, inflammatory conditions, and liver disease, before attributing elevation solely to malignancy 1, 6