@article{BourasKimLinetal.2023,
  author    = {Bouras, Emmanouil and Kim, Andre E. and Lin, Yi and Morrison, John and Du, Mengmeng and Albanes, Demetrius and Barry, Elizabeth L. and Baurley, James W. and Berndt, Sonja I. and Bien, Stephanie A. and Bishop, Timothy D. and Brenner, Hermann and Budiarto, Arif and Burnett-Hartman, Andrea and Campbell, Peter T. and Carreras-Torres, Robert and Casey, Graham and Cenggoro, Tjeng Wawan and Chan, Andrew T. and Chang-Claude, Jenny and Conti, David V. and Cotterchio, Michelle and Devall, Matthew and Diez-Obrero, Virginia and Dimou, Niki and Drew, David A. and Figueiredo, Jane C. and Giles, Graham G. and Gruber, Stephen B. and Gunter, Marc J. and Harrison, Tabitha A. and Hidaka, Akihisa and Hoffmeister, Michael and Huyghe, Jeroen R. and Joshi, Amit D. and Kawaguchi, Eric S. and Keku, Temitope O. and Kundaje, Anshul and Le Marchand, Loic and Lewinger, Juan Pablo and Li, Li and Lynch, Brigid M. and Mahesworo, Bharuno and M{\"a}nnist{\"o}, Satu and Moreno, Victor and Murphy, Neil and Newcomb, Polly A. and Ob{\´o}n-Santacana, Mireia and Ose, Jennifer and Palmer, Julie R. and Papadimitriou, Nikos and Pardamean, Bens and Pellatt, Andrew J. and Peoples, Anita R. and Platz, Elizabeth A. and Potter, John D. and Qi, Lihong and Qu, Conghui and Rennert, Gad and Ruiz-Narvaez, Edward and Sakoda, Lori C. and Schmit, Stephanie L. and Shcherbina, Anna and Stern, Mariana C. and Su, Yu-Ru and Tangen, Catherine M. and Thomas, Duncan C. and Tian, Yu and Um, Caroline Y. and Duijnhoven, Franzel JB. van and Van Guelpen, Bethany and Visvanathan, Kala and Wang, Jun and White, Emily and Wolk, Alicja and Woods, Michael O. and Ulrich, Cornelia M. and Hsu, Li and Gauderman, W James and Peters, Ulrike and Tsilidis, Konstantinos K.},
  title     = {Genome-wide interaction analysis of folate for colorectal cancer risk},
  journal   = {The American Journal of Clinical Nutrition},
  volume    = {118},
  number    = {5},
  issn      = {0002-9165},
  doi       = {10.25968/opus-3151},
  institution = {Fakult{\"a}t III - Medien, Information und Design},
  pages     = {881 -- 891},
  year      = {2023},
  abstract  = {Background: Epidemiological and experimental evidence suggests that higher folate intake is associated with decreased colorectal cancer (CRC) risk; however, the mechanisms underlying this relationship are not fully understood. Genetic variation that may have a direct or indirect impact on folate metabolism can provide insights into folate's role in CRC. Objectives: Our aim was to perform a genome-wide interaction analysis to identify genetic variants that may modify the association of folate on CRC risk. Methods: We applied traditional case-control logistic regression, joint 3-degree of freedom, and a 2-step weighted hypothesis approach to test the interactions of common variants (allele frequency >1\%) across the genome and dietary folate, folic acid supplement use, and total folate in relation to risk of CRC in 30,550 cases and 42,336 controls from 51 studies from 3 genetic consortia (CCFR, CORECT, GECCO). Results: Inverse associations of dietary, total folate, and folic acid supplement with CRC were found (odds ratio [OR]: 0.93; 95\% confidence interval [CI]: 0.90, 0.96; and 0.91; 95\% CI: 0.89, 0.94 per quartile higher intake, and 0.82 (95\% CI: 0.78, 0.88) for users compared with nonusers, respectively). Interactions (P-interaction < 5×10-8) of folic acid supplement and variants in the 3p25.2 locus (in the region of Synapsin II [SYN2]/tissue inhibitor of metalloproteinase 4 [TIMP4]) were found using traditional interaction analysis, with variant rs150924902 (located upstream to SYN2) showing the strongest interaction. In stratified analyses by rs150924902 genotypes, folate supplementation was associated with decreased CRC risk among those carrying the TT genotype (OR: 0.82; 95\% CI: 0.79, 0.86) but increased CRC risk among those carrying the TA genotype (OR: 1.63; 95\% CI: 1.29, 2.05), suggesting a qualitative interaction (P-interaction = 1.4×10-8). No interactions were observed for dietary and total folate. Conclusions: Variation in 3p25.2 locus may modify the association of folate supplement with CRC risk. Experimental studies and studies incorporating other relevant omics data are warranted to validate this finding.},
  subject      = {Folate},
  language  = {en}
}