Infection Rate May Indicate a Future Diagnosis of Cancer

In an article published in Cancer Immunology Research, researchers suggested that immune suppression and increased infection could occur during the precancerous period.¹

However, cancer can occur through a lifespan, therefore the authors indicated that further research is necessary to clarify these precancer trends.

"Cancer can develop in an inflammatory environment caused by infections, immunity disruption, exposure to chemical carcinogens, or chronic or genetic conditions," co-author of the study Shinako Inaida, PhD, a visiting researcher at the Graduate School of Medicine at Kyoto University in Japan, said in a press release.² "An individual's immunity is thought to be a factor in the development of cancer, but additional research is needed to understand the relationship among precancerous immunity, infections, and cancer development.”

In this 7-year case-control study of people ≥30 years of age, researchers looked to determine the prevalence of influenza, gastroenteritis, hepatitis, and pneumonia infections to indirectly assess whether infections correlated to the formation of malignant cancer. Using data extracted from a large medical claims database of a Japanese social health insurance system, researchers identified 2,354 people with their first cancer diagnosis occurring in the seventh year of the study for the case group and 48,395 people with no cancer diagnosis by the seventh year of the study for the control group.

The most common cancers diagnosed in the case group were digestive and gastrointestinal, head and neck, and stomach cancers. Other cancer types diagnosed in the case group included cancers within the following categories:

• Respiratory and thoracic

• Germ cell

• Genitourinary

• Liver

• Female breast

• Hematologic, blood, bone, and bone marrow

• Endocrine

• Unknown or other cancers

The yearly prevalence rates of influenza, gastroenteritis, hepatitis, and pneumonia infections were found to increase throughout the study period, with the case group experiencing higher rates of infection compared to the control group. Moreover, age-adjusted odds ratios (OR) and 95% confidence intervals (CI) in cases 1 year before cancer detection were significantly higher. During this year, the infection prevalence rates for the case group were higher than the control group by 18% for influenza (OR, 1.29; 95% CI, 1.14-1.46), 46.1% for gastroenteritis (OR. 1.60; 95% CI, 1.41-1.82), 232.1% for hepatitis (OR, 3.38; 95% CI, 2.12-5.37), and 135.9% for pneumonia (OR, 2.36; 95% CI, 1.79-3.13). 

In patients with influenza infections, significant ORs were found only in the second and sixth years before cancer diagnosis. Further, for each cancer site, an increased rate of infection prior to cancer diagnosis was observed.

The researchers also found that certain infections appeared to have a greater correlation with specific cancer types. For example, the odds of influenza infection just before cancer detection were highest for those who developed male germ cell cancers. Additionally, the odds of pneumonia were found to be highest in those who later developed stomach cancer and the odds of hepatitis infection were highest in those who developed hematologic, blood, bone, or bone marrow cancers. 

"Interestingly, we found that infection afflicting a specific organ did not necessarily correlate with increased risk of cancer in the same organ," Inaida explained.

Notably, the researchers only extracted the first cancer diagnosis for each patient and given that the observation period was limited to 8 years, further cancer diagnoses may have been missed. The data also did not include information such as the grade or stage of tumors, which may have been important to estimating each precancerous period. 

Another limitation highlighted by the researchers was that patients with infection who did not visit the hospital may have been overlooked. Moreover, influenza vaccination status may prevent infection, although a patient's influenza vaccination record was not available in for this dataset. 

“Patients who feel unwell, potentially because of cancerous status, tend to see doctors more often,” the authors wrote. “Although our study considered four major infections, analysis of other infections and the timing of infection before malignant cancer detection, which can potentially be a factor for later cancer development, remains to be studied.” 

References:

1. Inaida S, Matsuno S. Previous Infection Positively Correlates to the Tumor Incidence Rate of Patients with Cancer. Cancer Immunology Research. doi:10.1158/2326-6066.CIR-19.0510.

2. Increased rate of infections may indicate a future cancer diagnosis [news release]. American Association for Cancer Research. Published April 17, 2020. eurekalert.org/pub_releases/2020-04/aafc-iro041520.php. Accessed April 17, 2020.