A modifiable risk factors atlas of lung cancer: A Mendelian randomization study

Abstract

Background There has been no study systematically assessing the causal effects of putative modifiable risk factors on lung cancer. In this study, we aimed to construct a modifiable risk factors atlas of lung cancer by using the two‐sample Mendelian randomization framework. Methods We included 46 modifiable risk factors identified in previous studies. Traits with p‐value smaller than 0.05 were considered as suggestive risk factors. While the Bonferroni corrected p‐value for significant risk factors was set to be 8.33 × 10−4. Results In this two‐sample Mendelian randomization analysis, we found that higher socioeconomic status was significantly correlated with lower risk of lung cancer, including years of schooling, college or university degree, and household income. While cigarettes smoked per day, time spent watching TV, polyunsaturated fatty acids, docosapentaenoic acid, eicosapentaenoic acid, and arachidonic acid in blood were significantly associated with higher risk of lung cancer. Suggestive risk factors for lung cancer were found to be serum vitamin A1, copper in blood, docosahexaenoic acid in blood, and body fat percentage. Conclusions This study provided the first Mendelian randomization assessment of the causality between previously reported risk factors and lung cancer risk. Several modifiable targets, concerning socioeconomic status, lifestyle, dietary, and obesity, should be taken into consideration for the development of primary prevention strategies for lung cancer.

Causal associations between dietary antioxidant vitamin intake and lung cancer: A Mendelian randomization study

“…Our results showed that a higher dietary retinol intake can promote the development of lung cancer, which is consistent with the serum retinol results (OR = 1.44, 95% CI, 1.01-2.06, p = 0.04) (42). The statistical power of MR analysis was more than 80%, increasing the reliability of our results.…”

“…Previous studies have shown that the occurrence of lung cancer is related to genetic and environmental factors, such as tobacco, alcohol, asbestos, and other chemical products (42). Oxidative stress in the respiratory system increases the production of pulmonary inflammation mediators and initiates or promotes the mechanisms of carcinogenesis (60).…”

“…Many MR studies have focused on the potential causal association between vitamins and cancer, such as circulating vitamins B, C, D, and E (37)(38)(39)(40)(41). For lung cancer, it has been shown that serum retinol may be a risk factor for lung cancer (42), while the other circulating antioxidant vitamins have no effect on lung cancer risk (37,39,42). However, due to the unique bioaccessibility of antioxidants, it has not been determined whether dietary antioxidants affect the incidence of lung cancer.…”

Identifying modifiable risk factors of lung cancer: Indications from Mendelian randomization

“…As for smoking behavior, three subtypes of such behavior indicated smoking is the most perilous factor for lung cancer and there is a dose-response relationship between the number of cigarettes per day and lung cancer. Our results were consistent with previous MR studies [ 10 , 15 ]. Considering that Shen et al included the number of cigarettes per day in their study, the causal relationship between smoking cessation and lung cancer from our study indicated quitting smoking might be effective in reducing the risk of lung cancer.…”

“…Furthermore, we hope to include some new potential risk factors (blood pressure) that have not been investigated in MR studies considering that Shen et al has demonstrated the potential risk factors of lung cancer, including socioeconomic status, lifestyle, dietary, and obesity [ 15 ]. Meanwhile, we selected three types of smoking behavior (smoking initiation, smoking cessation, and the number of cigarettes per day) and tried to give novel insights into smoking’s impact on lung cancer.…”