“Neovascular age-related macular degeneration (nAMD) is a leading cause of vision loss in older adults and is increasingly recognised as a manifestation of systemic ageing involving vascular and inflammatory pathways.”

A new research paper was published in Volume 18 of Ageing titled “Systemic cancer risk profile in neovascular age-related macular degeneration: insights into shared ageing-related mechanisms from a nationwide population-based study.”

The study was led by first author Hyeong Min Kim and corresponding author Hyewon Chung from Konkuk University College of Medicine and Konkuk University Medical Centre in Seoul, Republic of Korea.

Neovascular age-related macular degeneration (nAMD) is one of the leading causes of severe vision loss in older adults.

Although the disease primarily affects the retina, researchers increasingly recognise that it may reflect broader biological processes associated with ageing, including chronic inflammation, vascular dysfunction, and immune dysregulation.

These same mechanisms have also been implicated in the development of several cancers, raising questions about whether the two conditions may be biologically connected.

To explore this possibility, investigators analysed data from the Korean National Health Insurance Service, one of the world’s largest population-based healthcare databases.

The study included 334,091 individuals aged 50 years and older, including 83,742 patients with nAMD and 250,349 matched controls without the disease.

Participants were followed for up to 10 years, allowing researchers to evaluate both overall cancer incidence and risks for specific cancer types.

The analysis revealed that individuals with nAMD had a modest but statistically significant increase in overall cancer risk compared with matched controls.

However, the increased risk was not observed across all cancers. Instead, patients with nAMD showed elevated risks for several specific malignancies, including thyroid, kidney, pancreatic, lung, bladder, and prostate cancers, while no significant associations were found for many other cancer types.

One of the strongest associations was thyroid cancer, for which individuals with nAMD had an approximately 24% higher risk.

Increased risks were also observed for kidney, pancreatic, lung, bladder, and prostate cancers.

These findings suggest that nAMD may be associated with a selective pattern of cancer susceptibility rather than a generalised increase in cancer risk.

The researchers explored several biological explanations for these observations. One possibility involves angiogenesis, the process through which new blood vessels form.

Both nAMD and many cancers depend on signalling pathways involving vascular endothelial growth factor (VEGF), a key regulator of abnormal blood vessel growth.

However, the authors suggest that shared angiogenic pathways alone are unlikely to fully explain the observed associations.

The study also points to broader ageing-related mechanisms that may contribute to both conditions.

Chronic low-grade inflammation, cellular senescence, immune dysregulation, oxidative stress, and extracellular matrix remodelling have all been implicated in the development of nAMD and cancer.

The authors propose that these overlapping processes may form part of a common ageing–inflammation–vasculature axis that influences disease susceptibility later in life.

In addition, the investigators discuss emerging evidence that nAMD and several of the associated cancers may share overlapping genetic risk factors.

Biological pathways involving complement activation, lipid metabolism, inflammation, and extracellular matrix regulation have been linked to both retinal degeneration and tumour development, suggesting that common vulnerabilities may extend beyond the eye.

“These findings indicate that nAMD may serve as a clinical marker of systemic vulnerability to selected cancers, possibly through shared angiogenic, inflammatory, and polygenic mechanisms underlying ageing-related disease susceptibility.”

According to the authors, the findings should be interpreted with caution. Although the observed increases in cancer risk were statistically significant, they were relatively modest and do not support specialised cancer screening solely on the basis of an nAMD diagnosis.

Instead, the results suggest that nAMD may serve as a clinical indicator of broader systemic ageing processes that also contribute to susceptibility to selected cancers.

Overall, this nationwide population-based study provides new evidence that neovascular age-related macular degeneration may be associated with increased risks of several specific cancers.

The findings support the growing recognition that ageing-related diseases often share common biological pathways and highlight the importance of investigating vascular, inflammatory, and genetic mechanisms across multiple organ systems.

Future research may help clarify how these shared ageing processes contribute to both vision loss and cancer development.

Article: Systemic cancer risk profile in neovascular age-related macular degeneration: insights into shared aging-related mechanisms from a nationwide population-based study

Source: Impact Journals LLC