Study suggests vitamin D deficiency opens the door to cancer, and risk increases with age

Low exposure to ultraviolet B (UVB) light may be linked to an increased risk of colorectal cancer (CRC)—and this association appears to increase with age, according to an analysis published in BMC Public Health.

Factors such as obesity, a sedentary lifestyle, and consumption of high-fat diets have all been linked to increased CRC risk. However, according to Vidya Lakshmi Purushothaman, MAS, MPH, of the University of California and the Global Health Policy Institute in San Diego, California, and colleagues, research suggests that vitamin D deficiency—particularly deficiency that has been allowed to accumulate into old age—is another important risk factor. And, they added, there is evidence that increasing vitamin D levels via UVB exposure has protective effect against this and other forms of cancer.

“The association between UVB exposure and global incidence of colorectal cancer was first analyzed in an ecological study where simple linear regression and multiple linear regression methods were used to study the inverse association between UVB exposure and incidence of CRC,” they explained. “In this study, the age-adjusted crude incidence rates of colorectal cancer were higher at latitudes distant from the equator (R2=0.50, P<0.001). In the adjusted model of that study, UVB exposure (adjusted for cloudiness) was inversely associated with age adjusted CRC crude incidence rates (P=0.01), after controlling for covariates. However, age-dependent strength of the inverse association between UVB exposure and colorectal cancer was not explored in that study.”

For their analysis, Purushothaman and colleagues assessed the effect of age on the inverse association between UVB exposure and CRC incidence, adjusting for influential covariates including stratospheric ozone, diet, smoking prevalence, life expectancy, and wealth.

The study authors found that “Polynomial regression models for each age group between adjusted UVB estimates and CRC crude incidence rate showed a stronger inverse association for older age groups compared to younger age groups. The overall P-value of the polynomial model was statistically significant for every age group. Also, the overall R2 of the polynomial model increased with age and the highest R2 (0.62) was obtained for 64–75 years of age. The overall R2 value of the polynomial model for countries in northern hemisphere for over 75 years of age was higher than that for countries in southern hemisphere before adjusting for covariates.”

“This study supports the need for adequate public health programs to avoid vitamin D inadequacy at national and global levels, whether through screening those at risk, through selective supplementation, or through population-based measures such as food fortification,” they wrote. “Future studies can aim at identifying the cancer types which show significant improvement with vitamin D supplementation. Studying the association between chronic vitamin D deficiency and CRC incidence will help in understanding the necessity for population-wide screening programs for vitamin D deficiency, especially in regions with inadequate UVB exposure. These programs may help decrease risk of CRC, as well as other cancers whose risk is associated with vitamin D deficiency, for high-risk populations whose vitamin D deficiency has been especially chronic.”

For this study, Purushothaman and colleagues pulled recent age-stratified, country-specific crude rates of CRC in 2018 for 186 nations around the globe using the Global Cancer (GLOBOCAN) database; they then used data from NASA’s EOS Aura spacecraft to estimate UVB levels in 2017, adjusted for cloud cover and aerosols, for 166 countries.

“Multiple linear regression was used to investigate the association between crude incidence rates of colorectal cancer and UVB estimate adjusting for urbanization, skin pigmentation, smoking, animal consumption, per capita GDP, and life expectancy,” they explained. “Statistical analysis was followed by geospatial visualization by producing choropleth maps.” Data for all covariates were available for 148 countries.

Purushothaman and colleagues found that there was a negative correlation between incidence of CRC and UVB exposure, with the correlation increasing in strength as age increased. However, in a multiple linear regression model, they noted, UVB was only inversely associated with crude incidence rates of CRC for age groups above 45 years old after controlling for covariates (P<0.05), with the highest risk among those ages 64-75 years and >75 years.

“The association between UVB estimates and crude incidence rates of CRC was not statistically significant in age groups below 45 years, after controlling for covariates,” they added.

“The main strength of this study is the novelty of assessing the age-dependent inverse relationship between UVB exposure and CRC incidence,” Purushothaman and colleagues wrote. “The unadjusted analysis included 166 countries in comparison to 139 countries in a previous study. The results of this analysis are in line with the previous study in having obtained a significant inverse association between UVB exposure and incidence of colorectal cancer…We suggest that several risk factors for later-age development of CRC may derive from chronic exposures, and we suggest that vitamin D deficiency is among these.”

Study limitations included that data for all variables were only available for 148 of 186 countries, potentially reducing the strength of associations, and that UVB is “an imperfect proxy measure” for assessing vitamin D levels and cannot account for factors such as vitamin D supplementation, clothing cover area, altitude over sea level, air pollution, and environmental chemicals that may be relevant when examining vitamin deficiencies.

The study authors also noted that the results of this study “cannot be applied directly at the level of individuals due to ecological fallacy.”

  1. Researchers found a reverse association between exposure to ultraviolet B (UVB) light from the sun and crude incidence rates of colorectal cancer (CRC), and the strength of the association increased with older age.

  2. The study authors argued that this study supports the need for adequate public health programs to avoid vitamin D inadequacy at national and global levels.

John McKenna, Associate Editor, BreakingMED™

Coauthor Mackey is a senior editorial board member of BMC Public Health and an employee of the startup company S-3 Research LLC, a startup funded and currently supported by the National Institutes of Health–National Institute on Drug Abuse through a Small Business Innovation and Research contract for opioid-related social media research and technology commercialization.

Cat ID: 23

Topic ID: 78,23,494,730,16,23,192,925