High dietary Vitamin A linked to increased risk of "lung cancer": A "dietetic warning" for public health

A study published in Frontiers in Nutrition has shown that a high dietary intake of retinol and carotenoid is related to an increased risk of lung cancer and adenocarcinoma. This mendelian randomised (MR) analysis does not support the dietary intake of vitamins to prevent lung cancer, and there is no supporting evidence between the protective role of nutritional vitamins and the development of lung cancer. The study delivered an important public dietary and healthy message.

Lung cancer is the primary cause of death among men and is ranked third among women. The risk factors for lung cancer are smoking, body mass index, asbestos, and air pollution. Genetics plays an essential role in malignant lung tumors. Epidermal Growth Factor Receptor mutations are closely related to lung cancer in non-smokers, while Kirsten rat sarcoma viral oncogene (KRAS) mutations are related to smokers.

The data on the association between antioxidants like retinol and lung cancer remains inconsistent. Some studies show that antioxidant vitamins or minerals are related to increased cancer risk, prostate cancer, and lung cancer. In contrast, other studies conclude that retinol reduces the risk of lung cancer. A study conducted by Narita et al. related dietary consumption of retinol to an increased risk of lung cancer among men in Japan. 

Serum retinol may be a risk factor for lung cancer compared to the other circulating antioxidant vitamins having no risk of lung cancer. The association remains controversial and unclear. To estimate the causal association between dietary antioxidant vitamin intake and lung cancer risk, a two-sample MR analysis based on a large-scale genome-wide association study (GWAS) for vitamin A (retinol), carotene, vitamin C, and vitamin E, lung cancer, squamous cell lung cancer, and lung adenocarcinoma was performed by two researchers by Dr. Hang Zhao and Xiaolin Jin from the Peking University China-Japan Friendship School of Clinical Medicine, Department of Urology of China-Japan Friendship Hospital and the Department of International Physical Examination Center at The First Affiliated Hospital of China Medical University.

The critical points of the study are:

• Higher dietary retinol intake was causally associated with lung cancer, with an odds ratio (OR) of 1.844 and p-values of 0.00009.

• The OR for squamous cell lung cancer and lung adenocarcinoma was 2.162 and 1.706, with a p-value of 0.022 and 0.021, respectively. This suggests that the association is significant.

• There was a positive correlation between carotene and lung adenocarcinoma, with an OR of 1.510 and a p-value of 0.049.

• There was no significant relationship between vitamin C and vitamin E in lung cancer.

As per MR analysis, higher dietary retinol increases the risk of lung cancer and may have a causal effect on squamous cell cancer and lung adenocarcinoma. Carotene increases the risk of lung adenocarcinoma. Further studies should be conducted to determine the relationship between specific vitamin types and more lung cancer subtypes.

The two researchers said, " The biggest strength was the use of MR analysis, most necessary for randomized controlled trials. And it reduces the likelihood of exposing subjects to unnecessary risk and harm." They wrote, " The findings of our study were validated due to Cochran's Q-test, MR–Egger, MRPRESSO, and Steiger filtering methods."

They said we used p < 5 × 10−6 as the threshold for IV selection, which may lead to weak instrumental bias.

Reference:

Zhao H and Jin X (2022) Causal associations between dietary antioxidant vitamin intake and lung cancer: A Mendelian randomization study. Front. Nutr. 9:965911.