Cancer incidence following non-neoplastic medical conditions: a prospective population-based cohort study

Abstract

Background and purpose: Many non-neoplastic diseases have been established to be tumorigenic, and cancers are sometimes misdiagnosed as non-neoplastic diseases. We conducted a comprehensive registry-based study of site-specific cancer diagnosis risk following the diagnosis of any preceding medical condition (PMC) encoded by the International Classification of Diseases (ICD)-10 classification.

Material and methods: We analyzed healthcare data and cancer data for a random population-based sample of 2.5 million individuals living in Finland on January 1, 2000. Hazard ratios for each PMC and cancer pair were estimated using piecewise constant hazard regression models. P-values were corrected for multiple testing with the Bonferroni method.

Results: Several lifestyle-related PMCs were associated with the risk of cancer diagnosis, exemplified by chronic obstructive pulmonary disease and subsequent lung cancer diagnosis risk (female hazard ratio [HR] = 9.91, 95% confidence interval [CI]: 9.18-19.7, p-adj. < 0.0001; male HR = 5.69, 95% CI: 5.43-5.96, p-adj. < 0.0001). Diagnosis risk of ill-defined cancers appeared to increase following diagnosis of Alzheimer's disease (AD). We identified rare PMCs of potential interest.

Interpretation: A considerable proportion of the statistically significant associations were explainable by tobacco smoking and alcohol use. The enrichment of ill-defined cancer diagnoses in persons with AD, together with the overall inverse association between AD and cancer, may reflect underdiagnosis of cancer in this patient population. Our results provide a useful resource for research on the prevention and early detection of cancer.

Figure 1

Manhattan plot of preceding medical conditions (PMCs) at the three-character level of ICD-10 and cancer diagnosis risk for each cancer site for women (A) and men (B). Complete results are available in the Supplementary material. Sorted ICD-10-codes (x-axis) and log-transformed p-values (y-axis) are presented, with each point signifying a PMC-cancer pair. Point color alternates between sites. Solid horizontal lines denote a Bonferroni-adjusted p-value of 0.05. Y-axis values are cut at negative log10 value of 100. An abbreviation key is presented in Table 2.

Figure 2

Hierarchical clustering of binary logarithms of common three-character level ICD-10 code (columns) and cancer (rows) hazard ratio estimates, with blue color indicating a decreased cancer diagnosis risk, red indicating an increased cancer diagnosis risk, and green indicating a missing data point. Men in image A, women in image B.