Circulating vitamin D concentration and risk of seven cancers: Mendelian randomisation study.
GAME-ON Network (CORECT, DRIVE, ELLIPSE, FOCI-OCAC, TRICL-ILCCO)
MetadataShow full item record
Objective To determine if circulating concentrations of vitamin D are causally associated with risk of cancer.Design Mendelian randomisation study.Setting Large genetic epidemiology networks (the Genetic Associations and Mechanisms in Oncology (GAME-ON), the Genetic and Epidemiology of Colorectal Cancer Consortium (GECCO), and the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortiums, and the MR-Base platform).Participants 70 563 cases of cancer (22 898 prostate cancer, 15 748 breast cancer, 12 537 lung cancer, 11 488 colorectal cancer, 4369 ovarian cancer, 1896 pancreatic cancer, and 1627 neuroblastoma) and 84 418 controls.Exposures Four single nucleotide polymorphisms (rs2282679, rs10741657, rs12785878 and rs6013897) associated with vitamin D were used to define a multi-polymorphism score for circulating 25-hydroxyvitamin D (25(OH)D) concentrations.Main outcomes measures The primary outcomes were the risk of incident colorectal, breast, prostate, ovarian, lung, and pancreatic cancer and neuroblastoma, which was evaluated with an inverse variance weighted average of the associations with specific polymorphisms and a likelihood based approach. Secondary outcomes based on cancer subtypes by sex, anatomic location, stage, and histology were also examined.Results There was little evidence that the multi-polymorphism score of 25(OH)D was associated with risk of any of the seven cancers or their subtypes. Specifically, the odds ratios per 25 nmol/L increase in genetically determined 25(OH)D concentrations were 0.92 (95% confidence interval 0.76 to 1.10) for colorectal cancer, 1.05 (0.89 to 1.24) for breast cancer, 0.89 (0.77 to 1.02) for prostate cancer, and 1.03 (0.87 to 1.23) for lung cancer. The results were consistent with the two different analytical approaches, and the study was powered to detect relative effect sizes of moderate magnitude (for example, 1.20-1.50 per 25 nmol/L decrease in 25(OH)D for most primary cancer outcomes. The Mendelian randomisation assumptions did not seem to be violated.Conclusions There is little evidence for a linear causal association between circulating vitamin D concentration and risk of various types of cancer, though the existence of causal clinically relevant effects of low magnitude cannot be ruled out. These results, in combination with previous literature, provide evidence that population-wide screening for vitamin D deficiency and subsequent widespread vitamin D supplementation should not currently be recommended as a strategy for primary cancer prevention.
Version of record
GAME-ON Network (CORECT, DRIVE, ELLIPSE, FOCI-OCAC, TRICL-ILCCO)
Vitamin D Deficiency
Genetic Predisposition to Disease
Polymorphism, Single Nucleotide
Genome-Wide Association Study
Mendelian Randomization Analysis
License start date
BMJ (Clinical research ed.), 2017, 359 pp. j4761 - ?
Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by/4.0/
Showing items related by title, author, creator and subject.
A phase I pharmacokinetic and pharmacodynamic study of the oral mitogen-activated protein kinase kinase (MEK) inhibitor, WX-554, in patients with advanced solid tumours. Jamieson, D; Griffin, MJ; Sludden, J; Drew, Y; Cresti, N; Swales, K; Merriman, M; Allen, R; Bevan, P; Buerkle, M; Mala, C; Coyle, V; Rodgers, L; Dean, E; Greystoke, A; Banerji, U; Wilson, RH; Evans, TRJ; Anthoney, A; Ranson, M; Boddy, AV; Plummer, R (2016-11)We performed a multi-centre phase I study to assess the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of the orally available small molecule mitogen-activated protein kinase kinase (MEK) 1/2 inhibitor, WX-554, ...
Jiang, X; Finucane, HK; Schumacher, FR; Schmit, SL; Tyrer, JP; Han, Y; Michailidou, K; Lesseur, C; Kuchenbaecker, KB; Dennis, J; Conti, DV; Casey, G; Gaudet, MM; Huyghe, JR; Albanes, D; Aldrich, MC; Andrew, AS; Andrulis, IL; Anton-Culver, H; Antoniou, AC; Antonenkova, NN; Arnold, SM; Aronson, KJ; Arun, BK; Bandera, EV; Barkardottir, RB; Barnes, DR; Batra, J; Beckmann, MW; Benitez, J; Benlloch, S; Berchuck, A; Berndt, SI; Bickeböller, H; Bien, SA; Blomqvist, C; Boccia, S; Bogdanova, NV; Bojesen, SE; Bolla, MK; Brauch, H; Brenner, H; Brenton, JD; Brook, MN; Brunet, J; Brunnström, H; Buchanan, DD; Burwinkel, B; Butzow, R; Cadoni, G; Caldés, T; Caligo, MA; Campbell, I; Campbell, PT; Cancel-Tassin, G; Cannon-Albright, L; Campa, D; Caporaso, N; Carvalho, AL; Chan, AT; Chang-Claude, J; Chanock, SJ; Chen, C; Christiani, DC; Claes, KBM; Claessens, F; Clements, J; Collée, JM; Correa, MC; Couch, FJ; Cox, A; Cunningham, JM; Cybulski, C; Czene, K; Daly, MB; deFazio, A; Devilee, P; Diez, O; Gago-Dominguez, M; Donovan, JL; Dörk, T; Duell, EJ; Dunning, AM; Dwek, M; Eccles, DM; Edlund, CK; Edwards, DRV; Ellberg, C; Evans, DG; Fasching, PA; Ferris, RL; Liloglou, T; Figueiredo, JC; Fletcher, O; Fortner, RT; Fostira, F; Franceschi, S; Friedman, E; Gallinger, SJ; Ganz, PA; Garber, J; García-Sáenz, JA; Gayther, SA; Giles, GG; Godwin, AK; Goldberg, MS; Goldgar, DE; Goode, EL; Goodman, MT; Goodman, G; Grankvist, K; Greene, MH; Gronberg, H; Gronwald, J; Guénel, P; Håkansson, N; Hall, P; Hamann, U; Hamdy, FC; Hamilton, RJ; Hampe, J; Haugen, A; Heitz, F; Herrero, R; Hillemanns, P; Hoffmeister, M; Høgdall, E; Hong, Y-C; Hopper, JL; Houlston, R; Hulick, PJ; Hunter, DJ; Huntsman, DG; Idos, G; Imyanitov, EN; Ingles, SA; Isaacs, C; Jakubowska, A; James, P; Jenkins, MA; Johansson, M; Johansson, M; John, EM; Joshi, AD; Kaneva, R; Karlan, BY; Kelemen, LE; Kühl, T; Khaw, K-T; Khusnutdinova, E; Kibel, AS; Kiemeney, LA; Kim, J; Kjaer, SK; Knight, JA; Kogevinas, M; Kote-Jarai, Z; Koutros, S; Kristensen, VN; Kupryjanczyk, J; Lacko, M; Lam, S; Lambrechts, D; Landi, MT; Lazarus, P; Le, ND; Lee, E; Lejbkowicz, F; Lenz, H-J; Leslie, G; Lessel, D; Lester, J; Levine, DA; Li, L; Li, CI; Lindblom, A; Lindor, NM; Liu, G; Loupakis, F; Lubiński, J; Maehle, L; Maier, C; Mannermaa, A; Marchand, LL; Margolin, S; May, T; McGuffog, L; Meindl, A; Middha, P; Miller, A; Milne, RL; MacInnis, RJ; Modugno, F; Montagna, M; Moreno, V; Moysich, KB; Mucci, L; Muir, K; Mulligan, AM; Nathanson, KL; Neal, DE; Ness, AR; Neuhausen, SL; Nevanlinna, H; Newcomb, PA; Newcomb, LF; Nielsen, FC; Nikitina-Zake, L; Nordestgaard, BG; Nussbaum, RL; Offit, K; Olah, E; Olama, AAA; Olopade, OI; Olshan, AF; Olsson, H; Osorio, A; Pandha, H; Park, JY; Pashayan, N; Parsons, MT; Pejovic, T; Penney, KL; Peters, WHM; Phelan, CM; Phipps, AI; Plaseska-Karanfilska, D; Pring, M; Prokofyeva, D; Radice, P; Stefansson, K; Ramus, SJ; Raskin, L; Rennert, G; Rennert, HS; van Rensburg, EJ; Riggan, MJ; Risch, HA; Risch, A; Roobol, MJ; Rosenstein, BS; Rossing, MA; De Ruyck, K; Saloustros, E; Sandler, DP; Sawyer, EJ; Schabath, MB; Schleutker, J; Schmidt, MK; Setiawan, VW; Shen, H; Siegel, EM; Sieh, W; Singer, CF; Slattery, ML; Sorensen, KD; Southey, MC; Spurdle, AB; Stanford, JL; Stevens, VL; Stintzing, S; Stone, J; Sundfeldt, K; Sutphen, R; Swerdlow, AJ; Tajara, EH; Tangen, CM; Tardon, A; Taylor, JA; Teare, MD; Teixeira, MR; Terry, MB; Terry, KL; Thibodeau, SN; Thomassen, M; Bjørge, L; Tischkowitz, M; Toland, AE; Torres, D; Townsend, PA; Travis, RC; Tung, N; Tworoger, SS; Ulrich, CM; Usmani, N; Vachon, CM; Van Nieuwenhuysen, E; Vega, A; Aguado-Barrera, ME; Wang, Q; Webb, PM; Weinberg, CR; Weinstein, S; Weissler, MC; Weitzel, JN; West, CML; White, E; Whittemore, AS; Wichmann, H-E; Wiklund, F; Winqvist, R; Wolk, A; Woll, P; Woods, M; Wu, AH; Wu, X; Yannoukakos, D; Zheng, W; Zienolddiny, S; Ziogas, A; Zorn, KK; Lane, JM; Saxena, R; Thomas, D; Hung, RJ; Diergaarde, B; McKay, J; Peters, U; Hsu, L; García-Closas, M; Eeles, RA; Chenevix-Trench, G; Brennan, PJ; Haiman, CA; Simard, J; Easton, DF; Gruber, SB; Pharoah, PDP; Price, AL; Pasaniuc, B; Amos, CI; Kraft, P; Lindström, S (2019-01-25)Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total ...
A Cross-Cancer Genetic Association Analysis of the DNA Repair and DNA Damage Signaling Pathways for Lung, Ovary, Prostate, Breast, and Colorectal Cancer. Scarbrough, PM; Weber, RP; Iversen, ES; Brhane, Y; Amos, CI; Kraft, P; Hung, RJ; Sellers, TA; Witte, JS; Pharoah, P; Henderson, BE; Gruber, SB; Hunter, DJ; Garber, JE; Joshi, AD; McDonnell, K; Easton, DF; Eeles, R; Kote-Jarai, Z; Muir, K; Doherty, JA; Schildkraut, JM (2016-01)DNA damage is an established mediator of carcinogenesis, although genome-wide association studies (GWAS) have identified few significant loci. This cross-cancer site, pooled analysis was performed to increase the power to ...