Large Study: No Link Between Vitamin D, Lung Cancer Risk

Kristin Jenkins

May 02, 2018

The "largest and most comprehensive observational study to date" provides no evidence of an association between serum vitamin D concentrations and risk for subsequent lung cancer and thus does not support the idea that vitamin D is protective.

In a study by an international research group, pooled analysis of circulating vitamin D concentrations in prediagnostic blood from 5000 case-control pairs showed there was no dose-response relationship between select concentrations of vitamin D and lung cancer risk overall (odds ratio [OR], 0.98).

There was also no evidence of an association between vitamin D and lung cancer risk with respect to sex, age, smoking status, or histology, say Paul Brennan, MD, of the International Agency for Research on Cancer (IARC), in Lyon, France, and colleagues.

The analysis, embedded within the larger Lung Cancer Cohort Consortium (LC3) project, which involves more than two million participants from 20 cohorts in Asia, Australia, Europe and North America, was published online on April 2 in the Annals of Oncology.

"We interpret this to mean that vitamin D supplementation is unlikely to prove broadly effective for the primary prevention of lung cancer, regardless of whether or not you smoke," Brennan told Medscape Medical News. "The most important way to protect oneself against lung cancer is to stop smoking or never begin smoking," he added.

Unlike previous studies that relied on participants' self-reported tobacco use, this analysis identified recent tobacco exposure using measures of serum cotinine, a nicotine metabolite found in blood, the study authors note.

"Our results are important because many prevention strategies are still focused on vitamin D supplementation as a protective measure against a number of diseases, including cancer," said Brennan in a statement issued by the IARC.

Lung cancer remains the number one cause of cancer death globally. It accounts for nearly 1.7 million deaths annually and 20% of all cancer deaths overall. Although the primary cause of lung cancer is tobacco exposure, the lifetime risk for lung cancer among former smokers remains high, and never-smokers are also at risk.

"Given the high incidence of lung cancer worldwide, it is vital to prioritize efforts to reduce tobacco smoking and to identify additional preventive measures that may help to reduce the risk of the disease," said Christopher Wild, PhD, director of IARC, in the statement. "However, despite previous smaller studies suggesting that high vitamin D concentrations could protect against lung cancer, these new results do not support the idea of vitamin D supplementation for the primary prevention of lung cancer."

These findings are in sharp contrast to results from two previous meta-analyses that suggested that high concentrations of vitamin D may protect against lung cancer, the study authors point out.

The first meta-analysis, which included nine prospective studies, reported a 17% decrease in lung cancer risk among participants with different concentrations of circulating 25-hydroxyvitamin D (25[OH]D), the major metabolite of vitamin D, Brennan and colleagues note. Similarly, pooled results from the second meta-analysis showed a nonlinear inverse association between 25(OH)D and lung cancer risk.

"Ongoing cancer prevention trials testing vitamin D supplements may eventually provide additional evidence on whether or not increases in vitamin D concentrations translate to reductions in lung cancer risks or not," the investigators write.

For the current analysis, Brennan and colleagues identified 11,399 incident lung cancer cases with prediagnostic blood samples from LC3 cohort participants. A total of 5313 lung cancer patients subsequently underwent blood-based analysis. The study authors say they oversampled never-smokers and former smokers "to optimize the statistical power in smoking stratified risk analysis."

Matched control persons were randomly selected from cohort participants who were alive and cancer free at the time that each pair was diagnosed with lung cancer.

In addition to cohort, sex, date of blood collection, and date of birth, matching criteria included five categories of smoking status: never-smokers; former smokers who had quit less than 10 years previously; former smokers who had quit for 10 years or longer previously; "light" smokers of fewer than 15 cigarettes per day; and "heavy" smokers of 15 or more cigarettes daily.

Liquid chromatography and tandem mass spectrometry were used to measure and analyze serum cotinine. They were also used to separately analyze 25(OH)D-2 and 25(OH)D-3 concentrations; these concentrations were then combined to give an overall measure of 25(OH)D.

The study authors note that the analysis included participants whose vitamin D concentrations were between 7 and 41 nmol/L. "Even when we further restricted the reference category to include only those participants with vitamin D concentrations below 25 nmol/l, we found no evidence for an association for adequate vitamin D concentrations with lower lung cancer risk," they write.

Although consensus is lacking on how much vitamin D is enough, Brennan and colleagues point out that in a 2011 US Institute of Medicine report, serum vitamin D concentrations lower than 30 nmol/L were considered a risk for vitamin deficiency, and concentrations lower than 50 nmol/L conferred a risk for vitamin D inadequacy.

The LC3 was funded by the National Cancer Institute, the National Institutes of Health, and the National Health and Medical Research Council Australia. The analysis was supported by Cancer Council Australia, Cancer Research UK, the Research Council of Norway, and the Norwegian University of Science and Technology. Dr Brennan and coauthors have disclosed no relevant financial relationships.

Ann Oncol. Published online on April 2, 2018. Abstract

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