Inflammatory biomarkers found to be major contributors to the development of this type of cancer.
A study published in eBioMedicine identified specific biomarkers that could play a role in the development of endometrial cancer. It specifically sheds light on the role of inflammation and immune dysregulation in endometrial carcinogenesis, suggesting that these factors contribute significantly to the disease’s progression over time.
Endometrial cancer is a type of cancer that originates in the lining of the uterus, known as the endometrium. It is the most common cancer of the female reproductive system, typically affecting women after they’ve entered menopause. The exact cause tends to be linked to hormonal imbalances, particularly having more estrogen relative to progesterone, which can lead to the uncontrolled growth of the endometrial lining. Risk factors for developing this form of cancer include being obese, undergoing hormone therapy, age, a history of irregular periods, and certain genetic conditions like Lynch syndrome, a condition that increases the risk of developing various cancers due to inherited mutations in genes responsible for DNA repair.
Early symptoms of endometrial cancer often include abnormal vaginal bleeding, particularly after menopause, which can lead to early detection. When diagnosed early, patients have a high survival rate. The disease is typically treated through surgery, radiation, hormone therapy, or chemotherapy depending on its stage.
While genetic mutations have long been recognized as contributors to endometrial cancer, the new study focuses on the role of inflammation, particularly low-grade chronic inflammation associated with conditions like obesity, in its development.
Interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), and C-reactive protein (CPR) have all been linked to the disease in previous research. However, those studies often involved smaller sample sizes, limiting their ability to pinpoint specific pathways. This recent study, conducted with a larger population, aimed to address these limitations by using multiplex protein panels for further exploration. The team analyzed pre-diagnostic samples from 624 case-control pairs within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, which consists of over half a million participants recruited from various European countries.
The findings revealed that several circulating biomarkers, including IL-6, hepatocyte growth factor (HGF), phosphoinositide 3-kinase adapter protein 1 (PIK3AP1), and C-type lectin domain family 4 member G (CLEC4G), were positively associated with an increased risk of endometrial cancer. On the other hand, biomarkers like hydroxysteroid 11-beta dehydrogenase 1 (HSD11B1), Skp1/cullin/F-box protein (SCF), and chemokine ligand 25 (CCL25) are inversely associated with disease development, suggesting that these may provide protective effects against the cancer.
Another critical component of the study was the use of Mendelian Randomization analysis to verify the role of the biomarkers analyzed in endometrial cancer risk. This method allows researchers to analyze genetic data to establish potential causal relationships between specific proteins and cancer development. The findings showed a positive association between IL-6 and increased risk and a negative association with HSD11B1. These results suggest that IL-6, a known pro-inflammatory protein, may be a potential target for future prevention and treatment strategies for endometrial cancer.
The study also explored the relationship between protein clusters and cancer risk through sensitivity analyses. For example, proteins like TWEAK (TNF-related weak inducer of apoptosis) and MCP3 (CCL7) emerged as potential risk factors, further contributing to the understanding of how inflammation may influence cancer development. Overall, the findings could provide a baseline for more targeted approaches to reducing cancer risk, especially for individuals with higher levels of inflammation.
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Inflammatory proteins linked to higher risk of endometrial cancer
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