Colorectal cancer (CRC) risk is not just about genetics and diet - social and economic factors also play a role. This study from Karolinska Institute asked a fundamental question: do people with lower incomes, less education, or a history of mental illness have a different risk of developing colorectal cancer?
The question matters because if socioeconomic position (SEP) increases CRC risk, targeted screening and prevention efforts could be directed toward these groups. However, the evidence from different countries has been inconsistent - in the US, lower SEP seems to increase CRC risk, while older European studies found the opposite. This study used a modern, nationwide Swedish dataset to settle the question with high precision.
The study was published in BMC Cancer in 2026 and used the CRCBaSe database - a large registry linkage project - to analyze 78,043 CRC patients diagnosed in Sweden between 2010 and 2021, matched against 431,105 controls from the general population. This is one of the largest studies of its kind with individually linked socioeconomic and psychiatric data.
The study used CRCBaSe - a registry linkage of the Swedish Colorectal Cancer Registry (SCRCR) and national databases maintained by Statistics Sweden and the National Board of Welfare. Every person in Sweden has a unique personal identification number, allowing researchers to reliably link health records, income data, prescription data, and cancer registries across different government databases.
The design was a nested case-control study: each CRC patient was matched to 6 controls from the general population based on age, sex, and county of residence. Controls were free of CRC at the time of matching and could even serve as controls before being diagnosed with CRC themselves. This design is highly efficient for studying rare exposures while controlling for known confounders.
Four socioeconomic indicators were assessed: income (quartiles of individual disposable household income, averaged 2 years before diagnosis), education level (under 9 years, 9-12 years, over 12 years), civil status (living alone or not), and birth country (Sweden, Nordic, EU, non-EU). Mental illness history was identified from psychiatric hospital records since 1974, outpatient records since 2001, and national prescription data since 2005, capturing both severe cases requiring specialist care and milder cases treated with antidepressants only.
The income results were counterintuitive. Compared to the lowest-income group (Q1), individuals in the second-lowest income group (Q2) had a hazard ratio (HR) of 1.05 (95% CI 1.03-1.08) for CRC, and the middle-upper group (Q3) had an HR of 1.04 (95% CI 1.02-1.07). Both represent small but statistically significant increases in risk. However, the highest-income group (Q4) showed no increased risk (HR 0.98, 95% CI 0.96-1.01).
This non-linear pattern - middle incomes having higher risk than both the lowest and highest - may reflect lifestyle differences. People in Q2 and Q3 may have dietary habits, physical activity levels, or alcohol consumption patterns that differ from both the most deprived (Q1) and the most affluent (Q4). The effects were similar in men and women and across colon and rectal cancer separately.
Educational level was largely unrelated to overall CRC risk. The one exception was rectal cancer: individuals with more than 12 years of education had a modestly decreased rectal cancer risk (HR 0.91, 95% CI 0.88-0.94), possibly explained by the fact that smoking - a known rectal cancer risk factor - is less common in more highly educated populations. Civil status (living alone vs. with a partner) had no meaningful effect on CRC risk.
Birth country showed striking variation in CRC risk. Compared to Swedish-born residents, those born in other Nordic countries had an increased CRC rate (HR 1.06, 95% CI 1.02-1.10), and those born in other EU countries (outside the Nordics) also had elevated risk (HR 1.04, 95% CI 1.00-1.09). These findings are consistent with the fact that several Nordic neighbors - Norway and Denmark - have higher CRC incidence rates than Sweden.
In contrast, people born outside the EU had a substantially lower CRC rate (HR 0.80, 95% CI 0.77-0.83) compared to Swedish-born individuals. This is an example of the 'healthy migrant paradox' - immigrants, especially from more distant countries, often have healthier lifestyles and lower chronic disease rates when they first arrive, which may reflect pre-migration selection effects and dietary patterns.
The sex-stratified results showed some differences: the effect of Nordic origin was stronger in males (HR 1.10) than females (HR 1.02), and non-EU origin had a stronger protective effect in females (HR 0.74) than males (HR 0.85). These sex-based differences in how migration affects CRC risk may reflect varying dietary acculturation patterns or different exposures to CRC risk factors between immigrant men and women.
The mental illness findings were the most striking results of the study. People with a history of mild mental illness (primarily those treated with antidepressants without requiring specialist psychiatric care) had a significantly decreased CRC rate (HR 0.81, 95% CI 0.79-0.83). This protective association held even after adjusting for all socioeconomic indicators, suggesting it is not simply explained by income or education.
On the other end of the spectrum, a history of severe mental illness (requiring specialist psychiatric care) was associated with a markedly increased CRC rate (HR 1.84, 95% CI 1.74-1.95). When broken down by diagnosis, bipolar disorder carried the highest risk (HR 3.57), followed by severe depression (HR 1.66) and psychosis (HR 1.13). Crucially, adjusting for all socioeconomic position indicators did not explain away the severe mental illness risk - the increased rate remained independent of income, education, and birth country.
At the population level, the demographics reinforce this finding: among CRC cases, 2.0% had severe mental illness compared to 1.1% among controls - nearly double the proportion. For mild mental illness, the pattern was reversed: 10.6% of cases vs. 12.4% of controls had mild mental illness history.
Given the mental illness associations, the researchers specifically examined whether antidepressant medications themselves might be driving some of the risk patterns. The most prescribed antidepressants were SSRIs (selective serotonin reuptake inhibitors), with nearly 9% of all patients and controls having at least two SSRI prescriptions or over 90 defined daily doses.
When analyzed together, any antidepressant prescription reduced the CRC rate (HR 0.78, 95% CI 0.71-0.85). Individual medication classes showed different patterns: SSRIs reduced CRC risk (HR 0.94), TCAs reduced risk (HR 0.87), and lithium also reduced risk (HR 0.74) when analyzed alone. However, when all antidepressants were entered into the model simultaneously, lithium's effect reversed while SSRIs and TCAs retained protective associations.
Interestingly, SNRIs (serotonin-norepinephrine reuptake inhibitors) were associated with increased CRC risk (HR 1.10, 95% CI 1.03-1.18) in the combined model. This contrast between SSRI and SNRI effects suggests the protective mechanism may be specific to serotonin signaling - SSRIs block serotonin reuptake selectively, while SNRIs also affect norepinephrine, which may have different effects on colorectal biology. These are preliminary correlational findings and should not guide medication prescribing decisions.
The increased CRC risk associated with severe mental illness was independent of socioeconomic position, which rules out income or education alone as explanations. Several mechanisms may be at play: people with severe psychiatric illness have higher rates of smoking and unhealthy diets - both established CRC risk factors. Smoking is particularly relevant given the observed link to rectal cancer.
Another important factor is reduced participation in CRC screening. People with severe mental illness may be less likely to attend bowel cancer screening programs, meaning pre-cancerous polyps go undetected and unremoved. This could increase both incidence (by not removing precursors) and potentially explain why cancers are diagnosed at a later stage in this group.
There is also a possible pharmacological mechanism: some antipsychotic medications may actually protect against CRC (antipsychotics were associated with HR 0.43 in this study), while other biological pathways triggered by severe psychiatric illness - potentially involving inflammation, the gut microbiome, or stress-related hormonal dysregulation - could promote tumor development. The picture is complex and likely involves multiple interacting factors that future research will need to disentangle.
The main conclusion from this 11-year national study is that socioeconomic position has a relatively small and heterogeneous effect on CRC risk in Sweden - more similar to findings from Finland and Italy than to those from Denmark or the US, where low SEP more consistently increases risk. Sweden's universal healthcare system may buffer some of the health impacts that low SEP creates in more unequal countries.
However, the findings around severe mental illness as an independent CRC risk factor (nearly doubling CRC incidence) are clinically significant and novel. The fact that this risk persists after adjusting for socioeconomic factors suggests it is not just explained by deprivation - there are separate mechanisms linking severe psychiatric illness to colorectal cancer development that warrant investigation.
Practically, this study suggests that individuals with severe psychiatric illness should be actively supported in participating in CRC screening, as reduced screening uptake likely contributes to their elevated incidence. Understanding the potential protective role of specific antidepressant classes (SSRIs, TCAs, and possibly antipsychotics) could also open new avenues for chemoprevention research. Future studies should investigate whether improving screening access and modifying medication regimens in people with severe mental illness can reduce their elevated CRC burden.