Docosapentaenoic acid and lung cancer risk: A Mendelian randomization study

Abstract

Background Observational studies have shown that excessive dietary fat may be associated with lung carcinogenesis. However, findings from previous studies are inconsistent and it remains unclear whether docosapentaenoic acid (DPA), a kind of polyunsaturated fatty acid, is linked to the risk of lung cancer. The aim of this study is to investigate the causal effect of DPA on lung cancer with Mendelian randomization (MR) method. Methods With a two‐sample MR approach, we analyzed the summary data from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE, 8866 individuals of European ancestry) Consortium and International Lung Cancer Consortium (ILCCO, 11 348 lung cancer cases and 15 861 controls; European ancestry) to assess the possible causal relationship of DPA on the risk of lung cancer. Results Our results indicated that genetically predicted higher DPA level has a positive association with lung cancer, where 1% higher DPA was associated with a 2.01‐fold risk of lung cancer (odds ratio [OR]: 2.01, 95% CI = 1.34‐3.01; P = 7.40 × 10−4). Additionally, lung cancer was not a causal factor for DPA. The results of MR‐Egger regression analysis showed that there was no evidence for the presence of directional horizontal pleiotropy. Conclusions Genetically elevated DPA is positively associated with risk of lung cancer, and more work is needed to investigate the potential mechanisms.

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

“… 57 The MR study performed by Liu et al reported DPA, a kind of PUFA, was linked to the risk of lung cancer. 13 We extended the MR analysis to multiple types of PUFA, and found inconsistent results with previous studies. 58 , 59 , 60 The potential adverse effects of other PUFA than 18:2, DHA, DPA, EPA, and AA on lung cancer patients should be considered when developing dietary guidelines on cancer prevention.…”

“…Furthermore, higher copper level increases oxidative stress, damages large biomolecules, and ultimately leads to oncogenesis 57 . The MR study performed by Liu et al reported DPA, a kind of PUFA, was linked to the risk of lung cancer 13 . We extended the MR analysis to multiple types of PUFA, and found inconsistent results with previous studies 58‐60 .…”

“…To date, we have recently used MR to examine the relationship between lung cancer and education, polyunsaturated fatty acid, minerals et al 13 , 14 , 15 , 16 , 17 However, there has been no study systematically assessing the causal effects of potentially modifiable risk factors on lung cancer. Here, we have extended our analysis to examine 46 potentially modifiable risk factors for lung cancer using a two‐sample MR framework.…”

Polyunsaturated Fatty Acid Levels and the Risk of Keratinocyte Cancer: A Mendelian Randomization Analysis

“…for the instrument selection for PUFA) and harmonised using the TwoSampleMR package in R (35). The selected IVs were largely consistent with previous studies that explored the associations between PUFA and other morbidities (21,22,24). Next, we retrieved summary data for the selected IVs for each PUFA for both the BCC and SCC analysis from the previous KC GWAS meta-analysis (31).…”

“…Previous MR studies have found significant associations between genetically predicted levels of particular PUFAs and the risk of cancer including; prostate cancer ( 21 ), lung cancer ( 22 ), and colorectal cancer ( 12, 23 ). However, previous MR studies found no association between PUFAs and the risk of cutaneous melanoma ( 24 ) and all cancer ( 23 ).…”