Browsing by Author "Du M"

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    Combining Asian and European genome-wide association studies of colorectal cancer improves risk prediction across racial and ethnic populations.
    (Springer Nature, 2023-10-02) Thomas M; Su Y-R; Rosenthal EA; Sakoda LC; Schmit SL; Timofeeva MN; Chen Z; Fernandez-Rozadilla C; Law PJ; Murphy N; Carreras-Torres R; Diez-Obrero V; van Duijnhoven FJB; Jiang S; Shin A; Wolk A; Phipps AI; Burnett-Hartman A; Gsur A; Chan AT; Zauber AG; Wu AH; Lindblom A; Um CY; Tangen CM; Gignoux C; Newton C; Haiman CA; Qu C; Bishop DT; Buchanan DD; Crosslin DR; Conti DV; Kim D-H; Hauser E; White E; Siegel E; Schumacher FR; Rennert G; Giles GG; Hampel H; Brenner H; Oze I; Oh JH; Lee JK; Schneider JL; Chang-Claude J; Kim J; Huyghe JR; Zheng J; Hampe J; Greenson J; Hopper JL; Palmer JR; Visvanathan K; Matsuo K; Matsuda K; Jung KJ; Li L; Le Marchand L; Vodickova L; Bujanda L; Gunter MJ; Matejcic M; Jenkins MA; Slattery ML; D'Amato M; Wang M; Hoffmeister M; Woods MO; Kim M; Song M; Iwasaki M; Du M; Udaltsova N; Sawada N; Vodicka P; Campbell PT; Newcomb PA; Cai Q; Pearlman R; Pai RK; Schoen RE; Steinfelder RS; Haile RW; Vandenputtelaar R; Prentice RL; Küry S; Castellví-Bel S; Tsugane S; Berndt SI; Lee SC; Brezina S; Weinstein SJ; Chanock SJ; Jee SH; Kweon S-S; Vadaparampil S; Harrison TA; Yamaji T; Keku TO; Vymetalkova V; Arndt V; Jia W-H; Shu X-O; Lin Y; Ahn Y-O; Stadler ZK; Van Guelpen B; Ulrich CM; Platz EA; Potter JD; Li CI; Meester R; Moreno V; Figueiredo JC; Casey G; Lansdorp Vogelaar I; Dunlop MG; Gruber SB; Hayes RB; Pharoah PDP; Houlston RS; Jarvik GP; Tomlinson IP; Zheng W; Corley DA; Peters U; Hsu L
    Polygenic risk scores (PRS) have great potential to guide precision colorectal cancer (CRC) prevention by identifying those at higher risk to undertake targeted screening. However, current PRS using European ancestry data have sub-optimal performance in non-European ancestry populations, limiting their utility among these populations. Towards addressing this deficiency, we expand PRS development for CRC by incorporating Asian ancestry data (21,731 cases; 47,444 controls) into European ancestry training datasets (78,473 cases; 107,143 controls). The AUC estimates (95% CI) of PRS are 0.63(0.62-0.64), 0.59(0.57-0.61), 0.62(0.60-0.63), and 0.65(0.63-0.66) in independent datasets including 1681-3651 cases and 8696-115,105 controls of Asian, Black/African American, Latinx/Hispanic, and non-Hispanic White, respectively. They are significantly better than the European-centric PRS in all four major US racial and ethnic groups (p-values < 0.05). Further inclusion of non-European ancestry populations, especially Black/African American and Latinx/Hispanic, is needed to improve the risk prediction and enhance equity in applying PRS in clinical practice.
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    Genome-wide interaction analysis of folate for colorectal cancer risk.
    (Elsevier B.V., 2023-11) Bouras E; Kim AE; Lin Y; Morrison J; Du M; Albanes D; Barry EL; Baurley JW; Berndt SI; Bien SA; Bishop TD; Brenner H; Budiarto A; Burnett-Hartman A; Campbell PT; Carreras-Torres R; Casey G; Cenggoro TW; Chan AT; Chang-Claude J; Conti DV; Cotterchio M; Devall M; Diez-Obrero V; Dimou N; Drew DA; Figueiredo JC; Giles GG; Gruber SB; Gunter MJ; Harrison TA; Hidaka A; Hoffmeister M; Huyghe JR; Joshi AD; Kawaguchi ES; Keku TO; Kundaje A; Le Marchand L; Lewinger JP; Li L; Lynch BM; Mahesworo B; Männistö S; Moreno V; Murphy N; Newcomb PA; Obón-Santacana M; Ose J; Palmer JR; Papadimitriou N; Pardamean B; Pellatt AJ; Peoples AR; Platz EA; Potter JD; Qi L; Qu C; Rennert G; Ruiz-Narvaez E; Sakoda LC; Schmit SL; Shcherbina A; Stern MC; Su Y-R; Tangen CM; Thomas DC; Tian Y; Um CY; van Duijnhoven FJ; Van Guelpen B; Visvanathan K; Wang J; White E; Wolk A; Woods MO; Ulrich CM; Hsu L; Gauderman WJ; Peters U; Tsilidis KK
    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.