Association between circulating inflammatory markers and adult cancer risk: a Mendelian randomization analysis

Yarmolinsky, James; Robinson, Jamie W.; Mariosa, Daniela; Karhunen, Ville; Huang, Jian; Dimou, Niki; Murphy, Neil; Burrows, Kimberley; Bouras, Emmanouil; Smith-Byrne, Karl; Lewis, Sarah J.; Galesloot, Tessel E.; Kiemeney, Lambertus A.; Vermeulen, Sita; Martin, Paul; Albanes, Demetrius; Hou, Lifang; Newcomb, Polly A.; White, Emily; Wolk, Alicja; Wu, Anna H.; Le Marchand, Loïc; Phipps, Amanda I.; Buchanan, Daniel D.; Landi, Maria Teresa; Stevens, Victoria; Wang, Ying; Albanes, Demetrios; Caporaso, Neil; Brennan, Paul; Amos, Christopher I.; Shete, Sanjay; Hung, Rayjean J.; Bickeböller, Heike; Risch, Angela; Houlston, Richard; Lam, Stephen; Tardon, Adonina; Chen, Chu; Bojesen, Stig E.; Johansson, Mattias; Wichmann, H-Erich; Christiani, David; Rennert, Gadi; Arnold, Susanne; Field, John K.; Le Marchand, Loic; Melander, Olle; Brunnström, Hans; Liu, Geoffrey; Andrew, Angeline; Kiemeney, Lambertus A.; Shen, Hongbing; Zienolddiny, Shan; Grankvist, Kjell; Johansson, Mikael; Teare, M. Dawn; Hong, Yun-Chul; Yuan, Jian-Min; Lazarus, Philip; Schabath, Matthew B.; Aldrich, Melinda C.; Eeles, Rosalind A.; Haiman, Christopher A.; Kote-Jarai, Zsofia; Schumacher, Fredrick R.; Benlloch, Sara; Al Olama, Ali Amin; Muir, Kenneth R.; Berndt, Sonja I.; Conti, David V.; Wiklund, Fredrik; Chanock, Stephen; Wang, Ying; Tangen, Catherine M.; Batra, Jyotsna; Clements, Judith A.; Grönberg, Henrik; Pashayan, Nora; Schleutker, Johanna; Albanes, Demetrius; Weinstein, Stephanie J.; Wolk, Alicja; West, Catharine M.L.; Mucci, Lorelei A.; Cancel-Tassin, Géraldine; Koutros, Stella; Sørensen, Karina Dalsgaard; Grindedal, Eli Marie; Neal, David E.; Hamdy, Freddie C.; Donovan, Jenny L.; Travis, Ruth C.; Hamilton, Robert J.; Ingles, Sue Ann; Rosenstein, Barry S.; Lu, Yong-Jie; Giles, Graham G.; MacInnis, Robert J.; Kibel, Adam S.; Vega, Ana; Kogevinas, Manolis; Penney, Kathryn L.; Park, Jong Y.; Stanfrod, Janet L.; Cybulski, Cezary; Nordestgaard, Børge G.; Nielsen, Sune F.; Brenner, Hermann; Maier, Christiane; Logothetis, Christopher J.; John, Esther M.; Teixeira, Manuel R.; Neuhausen, Susan L.; De Ruyck, Kim; Razack, Azad; Newcomb, Lisa F.; Lessel, Davor; Kaneva, Radka; Usmani, Nawaid; Claessens, Frank; Townsend, Paul A.; Castelao, Jose Esteban; Roobol, Monique J.; Menegaux, Florence; Khaw, Kay-Tee; Cannon-Albright, Lisa; Pandha, Hardev; Thibodeau, Stephen N.; Hunter, David J.; Kraft, Peter; Blot, William J.; Riboli, Elio; Zhao, Sizheng Steven; Gill, Dipender; Chanock, Stephen J.; Purdue, Mark P.; Davey Smith, George; Brennan, Paul; Herzig, Karl-Heinz; Järvelin, Marjo-Riitta; Amos, Chris I.; Hung, Rayjean J.; Dehghan, Abbas; Johansson, Mattias; Gunter, Marc J.; Tsilidis, Kostas K.; Martin, Richard M.

doi:10.1016/j.ebiom.2024.104991

Cited by 9 publications

(1 citation statement)

References 135 publications

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“…Previous research has highlighted the impact of specific blood metabolites, such as prostaglandins and leukotrienes, on skin cancer development by influencing the inflammatory response. Additionally, associations have been found between BCC and the human prothrombin complex, 25-hydroxyvitamin D, vitamin D, and PUFAs ( 8 – 11 ). Consequently, serum metabolites likely play a crucial role in BCC occurrence and progression.…”

Section: Introductionmentioning

confidence: 99%

Association between blood metabolites and basal cell carcinoma risk: a two-sample Mendelian randomization study

Wu,

Pan,

Wang

et al. 2024

Front. Endocrinol.

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BackgroundCirculating metabolites, which play a crucial role in our health, have been reported to be disordered in basal cell carcinoma (BCC). Despite these findings, evidence is still lacking to determine whether these metabolites directly promote or prevent BCC’s progression. Therefore, our study aims to examine the potential effects of circulating metabolites on BCC progression.Material and methodsWe conducted a two−sample Mendelian randomization (MR) analysis using data from two separate genome-wide association studies (GWAS). The primary study included data for 123 blood metabolites from a GWAS with 25,000 Finnish individuals, while the secondary study had data for 249 blood metabolites from a GWAS with 114,000 UK Biobank participants.GWAS data for BCC were obtained from the UK Biobank for the primary analysis and the FinnGen consortium for the secondary analysis. Sensitivity analyses were performed to assess heterogeneity and pleiotropy.ResultsIn the primary analysis, significant causal relationships were found between six metabolic traits and BCC with the inverse variance weighted (IVW) method after multiple testing [P < 4 × 10−4 (0.05/123)]. Four metabolic traits were discovered to be significantly linked with BCC in the secondary analysis, with a significance level of P < 2 × 10−4 (0.05/249). We found that all the significant traits are linked to Polyunsaturated Fatty Acids (PUFAs) and their degree of unsaturation.ConclusionOur research has revealed a direct link between the susceptibility of BCC and Polyunsaturated Fatty Acids and their degree of unsaturation. This discovery implies screening and prevention of BCC.

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Section: Introductionmentioning

confidence: 99%

Association between blood metabolites and basal cell carcinoma risk: a two-sample Mendelian randomization study

Wu,

Pan,

Wang

et al. 2024

Front. Endocrinol.

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Multi-omics and multi-stages integration identified a novel variant associated with silicosis risk

Jin,

Tao,

Zhang

et al. 2024

Arch Toxicol

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Mendelian randomization study on the association of circulating ketone bodies with lung cancer and respiratory diseases

Tang,

Zhuang,

2024

Sci Rep

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The liver produces various ketone bodies (KBs) including 3-Hydroxybutyrate (3-OHB), acetoacetate (AcAc), and acetone, with 3-OHB being the major component. Previous studies have shown that KBs protect against respiratory diseases; however, there is no evidence of a genetic link. To avoid biases existing in traditional observational studies, a two-sample Mendelian randomization (MR) analysis was carried out to investigate genetic causation and novel therapeutic uses for KBs. This study used databases from genome-wide association studies (GWAS) and single nucleotide polymorphisms as instrumental variables for KBs from a recently published metabonomics study ( n = 121,584) and respiratory diseases [lung cancer, n = 85,716; asthma, n = 127,669; chronic bronchitis, n = 450,422; chronic obstructive pulmonary disease (COPD), n = 468,475; FEV 1 /FVC < 0.7, n = 353,315] from their publicly available GWAS, respectively. Strong sets of instrumental variables ( P < 5 × 10 − 8 ) were selected, with inverse-variance weighted as the primary MR method. Sensitivity analyses included Cochran’s Q test, MR Egger, MR-PRESSO, leave-one-out test, and funnel plots. The Steiger test and reversed MR were used to exclude reverse causality. Additionally, independent replication MR studies were conducted using databases from another large public GWAS and similar methods as described above. After MR analyses and sensitivity filtering, we discovered a protective effect of 3-OHB on lung cancer (odds ratio [OR] = 0.771; 95% confidence interval [CI] = 0.648–0.916; P FDR =0.006), small cell carcinoma (OR = 0.485, 95% CI = 0.301–0.781, P FDR =0.006), asthma (OR = 0.585, 95% CI = 0.395–0.867, P FDR =0.010), chronic bronchitis (OR = 0.753, 95% CI = 0.570–0.994, P FDR =0.045), COPD (OR = 0.690, 95% CI = 0.535–0.890, P FDR =0.008) and lung function (OR = 0.970, 95%CI = 0.950–0.990, P FDR =0.008). In summary, our findings suggest that 3-OHB acts as a protective factor against lung cancer and respiratory diseases. However, heterogeneity implies that other mechanisms may also be involved in COPD improvement by 3-OHB. Supplementary Information The online version contains supplementary material available at 10.1038/s41598-024-81591-9.

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Association between circulating inflammatory markers and adult cancer risk: a Mendelian randomization analysis

Cited by 9 publications

References 135 publications

Association between blood metabolites and basal cell carcinoma risk: a two-sample Mendelian randomization study

Association between blood metabolites and basal cell carcinoma risk: a two-sample Mendelian randomization study

Multi-omics and multi-stages integration identified a novel variant associated with silicosis risk

Mendelian randomization study on the association of circulating ketone bodies with lung cancer and respiratory diseases

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