In a prospective analysis, having psoriasis at age 65+ was associated with higher subsequent colon cancer risk after adjustment for age, BMI, education, smoking, physical activity, and HT use. The hazard ratio for colon cancer was higher among those with severe compared to mild psoriasis. We also observed increased age-adjusted hazard ratios for lung and total cancer for psoriatic versus non-psoriatic patients but this was primarily due to confounding by cigarette smoking.
The majority of previous studies of psoriasis and cancer examined total, skin, and lymphoproliferative cancers, whereas only a few studies investigated associations with solid organ cancers. Several cohorts from Scandinavian countries, which included patients of wide age ranges, observed increased standardized incidence ratios (SIR) among psoriatic patients versus the general population for cancers as follows: total (by 27–40%), lung (by 40–110%), and colon (by 30–40%) [7
]. This increase was largely explained by an excess risk of skin cancer and lymphoproliferative cancers and/or cancers related to smoking. The main limitation of these Scandinavian studies was a potential bias due to lack of data about confounding variables. Another limitation is that those studies included only hospitalized patients, the majority of whom were hospitalized for psoriasis [7
]. Such patients likely have more severe psoriasis and, possibly, different cancer risk than other psoriatic patients [30
Only a few population-based studies have investigated psoriasis in relation to cancer, particularly solid organ cancers. A US study using the Medicaid administrative database reported an increase in total cancer risk by 78% for patients with severe psoriasis (those treated with systemic medication) and by 13% for those with mild disease compared to hypertensive patients [3
]. Recently, a nested case–control study by Brauchli et al. [9
] was the first to examine a link between psoriasis and cancer after adjusting for confounding variables, such as age, sex, calendar time, BMI, smoking, and benign tumors. In that study, psoriatic patients, 55% of whom were younger than 50 years at the time of psoriasis diagnosis, had slightly increased odds ratio of total cancer (OR = 1.13, 95% CI: 1.02–1.26), which was higher for psoriasis with duration ≥4 years: (OR = 1.50, 95% CI: 1.30–1.74) [9
]. The odds ratio for colorectal cancers was also increased with longer-duration psoriasis: (OR ~ 2.5, statistically significant, but exact data were not reported). The results for total and colorectal cancer are in agreement with the findings from the multivariate analysis in our study.
The biological mechanism explaining the relation between psoriasis and cancer is under investigation. Psoriasis is considered a systemic inflammatory disease not limited to the epidermis. It is characterized by immune deregulation: Th1 cells infiltrate the skin of a psoriatic patient and release inflammatory cytokines, such as interleukins (IL-1, IL-6), interferon-γ, and tumor necrosis factor-α, and stimulate dendritic cells, macrophages, and neutrophils, which induce epidermal hyperproliferation and hyperplasia [25
]. A deregulated immune system together with chronic inflammation may lead to mutations in dividing cells and errors in elimination of malignant cells, resulting in increased risk of cancer, especially, of lymphoproliferative cancers [34
Several lines of evidence link inflammation to colorectal cancer risk. Colorectal cancer is the only cancer for which the protective effect of an anti-inflammatory drug—aspirin has been clinically established [36
]. Several studies reported positive associations between C-reactive protein, a systemic inflammatory marker, and risk of colorectal cancer [37
]. In addition, positive associations have been shown between inflammatory bowel disease and colorectal cancer [36
] and between inflammatory bowel disease and psoriasis [42
]. Thus, chronic inflammation associated with psoriasis could result in subsequent colon cancer.
The major strength of our study is use of data from a large prospective population-based cohort linked to the already existing longitudinal Medicare dataset, which allowed for a cost-efficient analysis. To our knowledge, this is the first attempt to comprehensively establish a diagnosis of psoriasis through Medicare. Ascertainment of psoriasis via Medicare claims is free from usual bias such as non-response or recall. Furthermore, to our knowledge, this is only the second study that examined an association between psoriasis and incident cancers after adjustment for confounding variables.
Our study has limitations. Because we used the Medicare database for psoriasis ascertainment, we cannot exclude the possibility of incomplete coding and coding errors [44
]. The precise date of psoriasis onset was also unknown. We did not validate psoriasis diagnosis. However, validation studies conducted for other autoimmune diseases in Medicare, which used medical records as the gold standard, reported high sensitivities of the physician claims (0.90 for rheumatoid arthritis and 0.85 for systemic lupus erythematosus), and high positive predictive values (0.90 for both of these diseases) [44
]. Further, we conducted several sensitivity analyses and their results were robust. Finally, the most common diseases that can be misdiagnosed as psoriasis are seborrheic dermatitis and eczematous skin conditions, which are not known to be related to cancer [7
A limitation in our study is that power was limited for examining colon cancer risk in different subgroups. However, we observed a statistically significant increase in hazard ratio of proximal colon cancer by ~100% for psoriatic versus non-psoriatic patients. An additional limitation is that we lacked data about treatment. Although it is unlikely that systemic drugs or phototherapy affect the risk of solid organ cancers (other than skin cancer), this possibility cannot be fully excluded. Another potential concern is surveillance bias: patients with psoriasis could be more likely screened for cancer. Finally, our study was conducted among white elderly women in Iowa; results may not be generalizable to other age, race, gender, or other geographic settings.
In summary, our analysis showed that there was a positive association between psoriasis and colon cancer incidence. This supports the view that inflammation may play a role in colon carcinogenesis.