Sökning: WFRF:(Cerhan J. R.) > (2020-2023) > The association bet...
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000 | 05598naa a2200805 4500 | |
001 | oai:DiVA.org:uu-500750 | |
003 | SwePub | |
008 | 230424s2023 | |||||||||||000 ||eng| | |
024 | 7 | a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-5007502 URI |
024 | 7 | a https://doi.org/10.1016/j.ebiom.2023.1045102 DOI |
040 | a (SwePub)uu | |
041 | a engb eng | |
042 | 9 SwePub | |
072 | 7 | a ref2 swepub-contenttype |
072 | 7 | a art2 swepub-publicationtype |
100 | 1 | a Haycock, Philip C4 aut |
245 | 1 0 | a The association between genetically elevated polyunsaturated fatty acids and risk of cancer. |
264 | 1 | b Elsevier,c 2023 |
338 | a electronic2 rdacarrier | |
520 | a BACKGROUND: The causal relevance of polyunsaturated fatty acids (PUFAs) for risk of site-specific cancers remains uncertain.METHODS: Using a Mendelian randomization (MR) framework, we assessed the causal relevance of PUFAs for risk of cancer in European and East Asian ancestry individuals. We defined the primary exposure as PUFA desaturase activity, proxied by rs174546 at the FADS locus. Secondary exposures were defined as omega 3 and omega 6 PUFAs that could be proxied by genetic polymorphisms outside the FADS region. Our study used summary genetic data on 10 PUFAs and 67 cancers, corresponding to 562,871 cases and 1,619,465 controls, collected by the Fatty Acids in Cancer Mendelian Randomization Collaboration. We estimated odds ratios (ORs) for cancer per standard deviation increase in genetically proxied PUFA exposures.FINDINGS: Genetically elevated PUFA desaturase activity was associated (P < 0.0007) with higher risk (OR [95% confidence interval]) of colorectal cancer (1.09 [1.07-1.11]), esophageal squamous cell carcinoma (1.16 [1.06-1.26]), lung cancer (1.06 [1.03-1.08]) and basal cell carcinoma (1.05 [1.02-1.07]). There was little evidence for associations with reproductive cancers (OR = 1.00 [95% CI: 0.99-1.01]; Pheterogeneity = 0.25), urinary system cancers (1.03 [0.99-1.06], Pheterogeneity = 0.51), nervous system cancers (0.99 [0.95-1.03], Pheterogeneity = 0.92) or blood cancers (1.01 [0.98-1.04], Pheterogeneity = 0.09). Findings for colorectal cancer and esophageal squamous cell carcinoma remained compatible with causality in sensitivity analyses for violations of assumptions. Secondary MR analyses highlighted higher omega 6 PUFAs (arachidonic acid, gamma-linolenic acid and dihomo-gamma-linolenic acid) as potential mediators. PUFA biosynthesis is known to interact with aspirin, which increases risk of bleeding and inflammatory bowel disease. In a phenome-wide MR study of non-neoplastic diseases, we found that genetic lowering of PUFA desaturase activity, mimicking a hypothetical intervention to reduce cancer risk, was associated (P < 0.0006) with increased risk of inflammatory bowel disease but not bleeding.INTERPRETATION: The PUFA biosynthesis pathway may be an intervention target for prevention of colorectal cancer and esophageal squamous cell carcinoma but with potential for increased risk of inflammatory bowel disease. | |
650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Cancer och onkologi0 (SwePub)302032 hsv//swe |
650 | 7 | a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Cancer and Oncology0 (SwePub)302032 hsv//eng |
650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Allmänmedicin0 (SwePub)302242 hsv//swe |
650 | 7 | a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex General Practice0 (SwePub)302242 hsv//eng |
653 | a Cancer risk | |
653 | a Delta-5 desaturase | |
653 | a Delta-6 desaturase | |
653 | a Mendelian randomization | |
653 | a Omega 3 | |
653 | a Omega 6 | |
653 | a Polyunsaturated fatty acids | |
700 | 1 | a Borges, Maria Carolina4 aut |
700 | 1 | a Burrows, Kimberley4 aut |
700 | 1 | a Lemaitre, Rozenn N4 aut |
700 | 1 | a Burgess, Stephen4 aut |
700 | 1 | a Khankari, Nikhil K4 aut |
700 | 1 | a Tsilidis, Konstantinos K4 aut |
700 | 1 | a Gaunt, Tom R4 aut |
700 | 1 | a Hemani, Gibran4 aut |
700 | 1 | a Zheng, Jie4 aut |
700 | 1 | a Truong, Therese4 aut |
700 | 1 | a Birmann, Brenda M4 aut |
700 | 1 | a OMara, Tracy4 aut |
700 | 1 | a Spurdle, Amanda B4 aut |
700 | 1 | a Iles, Mark M4 aut |
700 | 1 | a Law, Matthew H4 aut |
700 | 1 | a Slager, Susan L4 aut |
700 | 1 | a Saberi Hosnijeh, Fatemeh4 aut |
700 | 1 | a Mariosa, Daniela4 aut |
700 | 1 | a Cotterchio, Michelle4 aut |
700 | 1 | a Cerhan, James R4 aut |
700 | 1 | a Peters, Ulrike4 aut |
700 | 1 | a Enroth, Stefan,d 1976-u Uppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab,Gyllensten4 aut0 (Swepub:uu)stenr451 |
700 | 1 | a Gharahkhani, Puya4 aut |
700 | 1 | a Le Marchand, Loic4 aut |
700 | 1 | a Williams, Ann C4 aut |
700 | 1 | a Block, Robert C4 aut |
700 | 1 | a Amos, Christopher I4 aut |
700 | 1 | a Hung, Rayjean J4 aut |
700 | 1 | a Zheng, Wei4 aut |
700 | 1 | a Gunter, Marc J4 aut |
700 | 1 | a Smith, George Davey4 aut |
700 | 1 | a Relton, Caroline4 aut |
700 | 1 | a Martin, Richard M4 aut |
710 | 2 | a Uppsala universitetb Institutionen för immunologi, genetik och patologi4 org |
773 | 0 | t EBioMedicined : Elsevierg 91q 91x 2352-3964 |
856 | 4 | u https://doi.org/10.1016/j.ebiom.2023.104510y Fulltext |
856 | 4 | u https://uu.diva-portal.org/smash/get/diva2:1752642/FULLTEXT01.pdfx primaryx Raw objecty fulltext:print |
856 | 4 8 | u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-500750 |
856 | 4 8 | u https://doi.org/10.1016/j.ebiom.2023.104510 |
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