Association of Carcinoembryonic Antigen with Mortality in an Insurance Applicant Population

Objectives.- To quantify the mortality risks associated with elevated levels of carcinoembryonic antigen (CEA). Background.- Carcinoembryonic antigen is cell surface glycoprotein and has been associated with the presence of high grade or metastatic cancers of the colon as well as other malignant and non-malignant disease. Prior publications have demonstrated the utility of CEA levels in the determination of mortality risk in life insurance applicants. The aim of this paper is to further characterize this risk with a larger set of data containing additional person-years of follow-up, more outcomes, and additional variables potentially associated with occult malignancy. Methods.- By use of the Social Security Death Index, mortality was examined in 321,574 insurance applicants age 50 years and older, who submitted blood samples to Clinical Reference Laboratories for testing including CEA. Results were stratified by age group and by CEA level (<5 ng/mL, 5 to 9.9 ng/mL, 10+ ng/mL), though other thresholds were tested. Mortality comparisons were carried out using Cox models and tabular methods with the 2015 smoker-distinct Valuation Basic Tables as a comparator. Results.- Relative mortality is increased at CEA levels above 4.0 ng/mL in both smokers and non-smokers. This association is persistent in Cox models when albumin, BMI and cholesterol are included as covariates. The strongest association with mortality risk occurred in the first 3-4 durations. The 3-year cumulative mortality ratio when using the 2015 VBT as baseline was 6.51 when comparing the group with CEA levels of 10+ ng/mL, compared to those with levels below 5.0 ng/mL. Conclusion.- This study shows that CEA is strongly associated with the risk of early excess mortality in life insurance applicants, and this risk appears not to be mitigated by consideration of other markers thought to be associated with occult malignancy.