Sepsis–Cancer Link Further Supported by National Cancer Institute Study

The results of a recent study, published in Clinical Infectious Diseases, indicate a significant link between sepsis and 15 cancers in elderly patients. Sepsis was associated with an increased risk of cancers of the lung, colon, rectum, and liver. Interestingly, prior sepsis infection was associated with a decreased risk for cancers of the breast, prostate, kidney, thyroid, and melanoma.

The US Centers for Disease Control and Prevention (CDC) state that about 1.5 million individuals in the United States will develop sepsis each year. Of those individuals, approximately 250,000 will die, making the infection a serious public health concern. Research has shown that patients with cancer who are undergoing chemotherapy are at increased risk of sepsis as the treatment can lead to neutropenia—abnormally low neutrophil count—which subsequently decreases a patient’s ability to fight off infection. What is less understood is the link between sepsis and the risk for cancer after infection.

To this end, investigators from the National Cancer Institute in Rockville, Maryland conducted an exploratory population-based case-control study to learn more about the association between sepsis and the risk for cancer. The team used the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database which is “a cancer surveillance program of the National Cancer Institute with information on demographics and tumor characteristics from 18 cancer registries covering approximately 28% of the US population,” according to the study authors. They identified 1,801,156 US adults who were first diagnosed with cancer between 1992 and 2013 (age range 66 to 115 years). The team also used a 5% random sample of Medicare beneficiaries to identify 200,000 individuals who were cancer-free to serve as controls. Inpatient Medicare claims were used to identify sepsis diagnosis and the team used logistic regression to identify associations with sepsis.

The results of the study indicated that “sepsis was significantly associated with increased risk for cancers of the colon (adjusted odds ratio [OR] = 1.12), rectum (1.13), liver (1.47), lung (1.17), and cervix (1.52), as well as acute myeloid leukemia (AML) (1.19), chronic myeloid leukemia (1.54), and myelodysplastic syndrome (1.30).” Conversely, inverse associations were found for cancers of the breast (adjusted OR=0.86), prostate (0.75), kidney (0.90), and thyroid (0.68), and melanoma (0.83), diffuse large B-cell lymphoma (0.89) and follicular lymphoma (0.65). Cancers of thyroid, prostate, colon, rectum, lung, liver, follicular lymphoma, melanoma, and AML were significantly associated with sepsis >5 years after sepsis diagnosis.

Of note, the study authors write that “although differences were small, cases were more likely to be smokers or alcohol abusers, and have hepatitis B virus infection, hepatitis C virus infection, diabetes mellitus, autoimmune disease, or cirrhosis.”

According to the investigators the etiologic effects of bacterial infections, inflammation, the use of antibiotics, or precursor conditions such as cirrhosis and colorectal polyps, may explain the association between sepsis and these cancers.

Some limitations of the study include that the results were seen in an elderly population, and, therefore, could not be generalizable to a younger population. Furthermore, the investigators were unable to fully assess confounding factors such as comorbidities, smoking, alcohol use, and viral infections. Additionally, because sepsis was identified using administrative claims, it is possible that some cases may have been misidentified.

Although they did not determine a causal link between sepsis and cancers, and, “the modest magnitude of these associations likely does not support close cancer surveillance of sepsis survivors,” the investigators concluded that sepsis can have “important long-term health consequences.”