Browsing by Author "van Duijnhoven, Fränzel J. B."

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    Genetically predicted circulating concentrations of micronutrients and risk of colorectal cancer among individuals of European descent: a Mendelian randomization study
    (Elsevier, 2021) Tsilidis, Konstantinos K.; Papadimitriou, Nikos; Dimou, Niki; Gill, Dipender; Lewis, Sarah J.; Martin, Richard M.; Murphy, Neil; Markozannes, Georgios; Zuber, Verena; Cross, Amanda J.; Burrows, Kimberley; Lopez, David S.; Key, Timothy J.; Travis, Ruth C.; Perez-Cornago, Aurora; Hunter, David J.; van Duijnhoven, Fränzel J. B.; Albanes, Demetrius; Arndt, Volker; Berndt, Sonja I.; Bézieau, Stéphane; Bishop, D. Timothy; Boehm, Juergen; Brenner, Hermann; Burnett-Hartman, Andrea; Campbell, Peter T.; Casey, Graham; Castellví-Bel, Sergi; Chan, Andrew T.; Chang-Claude, Jenny; de la Chapelle, Albert; Figueiredo, Jane C.; Gallinger, Steven J.; Giles, Graham G.; Goodman, Phyllis J.; Gsur, Andrea; Hampe, Jochen; Hampel, Heather; Hoffmeister, Michael; Jenkins, Mark A.; Keku, Temitope O.; Kweon, Sun-Seog; Larsson, Susanna C.; Le Marchand, Loic; Li, Christopher I.; Li, Li; Lindblom, Annika; Martín, Vicente; Milne, Roger L.; Moreno, Victor; Nan, Hongmei; Nassir, Rami; Newcomb, Polly A.; Offit, Kenneth; Pharoah, Paul D. P.; Platz, Elizabeth A.; Potter, John D.; Qi, Lihong; Rennert, Gad; Sakoda, Lori C.; Schafmayer, Clemens; Slattery, Martha L.; Snetselaar, Linda; Schenk, Jeanette; Thibodeau, Stephen N.; Ulrich, Cornelia M.; Van Guelpen, Bethany; Harlid, Sophia; Visvanathan, Kala; Vodickova, Ludmila; Wang, Hansong; White, Emily; Wolk, Alicja; Woods, Michael O.; Wu, Anna H.; Zheng, Wei; Bueno-de-Mesquita, Bas; Boutron-Ruault, Marie-Christine; Hughes, David J.; Jakszyn, Paula; Kühn, Tilman; Palli, Domenico; Riboli, Elio; Giovannucci, Edward L.; Banbury, Barbara L.; Gruber, Stephen B.; Peters, Ulrike; Gunter, Marc J.; Epidemiology, School of Public Health
    Background: The literature on associations of circulating concentrations of minerals and vitamins with risk of colorectal cancer is limited and inconsistent. Evidence from randomized controlled trials (RCTs) to support the efficacy of dietary modification or nutrient supplementation for colorectal cancer prevention is also limited. Objectives: To complement observational and RCT findings, we investigated associations of genetically predicted concentrations of 11 micronutrients (β-carotene, calcium, copper, folate, iron, magnesium, phosphorus, selenium, vitamin B-6, vitamin B-12, and zinc) with colorectal cancer risk using Mendelian randomization (MR). Methods: Two-sample MR was conducted using 58,221 individuals with colorectal cancer and 67,694 controls from the Genetics and Epidemiology of Colorectal Cancer Consortium, Colorectal Cancer Transdisciplinary Study, and Colon Cancer Family Registry. Inverse variance-weighted MR analyses were performed with sensitivity analyses to assess the impact of potential violations of MR assumptions. Results: Nominally significant associations were noted for genetically predicted iron concentration and higher risk of colon cancer [ORs per SD (ORSD): 1.08; 95% CI: 1.00, 1.17; P value = 0.05] and similarly for proximal colon cancer, and for vitamin B-12 concentration and higher risk of colorectal cancer (ORSD: 1.12; 95% CI: 1.03, 1.21; P value = 0.01) and similarly for colon cancer. A nominally significant association was also noted for genetically predicted selenium concentration and lower risk of colon cancer (ORSD: 0.98; 95% CI: 0.96, 1.00; P value = 0.05) and similarly for distal colon cancer. These associations were robust to sensitivity analyses. Nominally significant inverse associations were observed for zinc and risk of colorectal and distal colon cancers, but sensitivity analyses could not be performed. None of these findings survived correction for multiple testing. Genetically predicted concentrations of β-carotene, calcium, copper, folate, magnesium, phosphorus, and vitamin B-6 were not associated with disease risk. Conclusions: These results suggest possible causal associations of circulating iron and vitamin B-12 (positively) and selenium (inversely) with risk of colon cancer.
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    Genome-wide Interaction Study with Smoking for Colorectal Cancer Risk Identifies Novel Genetic Loci Related to Tumor Suppression, Inflammation, and Immune Response
    (American Association for Cancer Research, 2023) Carreras-Torres, Robert; Kim, Andre E.; Lin, Yi; Díez-Obrero, Virginia; Bien, Stephanie A.; Qu, Conghui; Wang, Jun; Dimou, Niki; Aglago, Elom K.; Albanes, Demetrius; Arndt, Volker; Baurley, James W.; Berndt, Sonja I.; Bézieau, Stéphane; Bishop, D. Timothy; Bouras, Emmanouil; Brenner, Hermann; Budiarto, Arif; Campbell, Peter T.; Casey, Graham; Chan, Andrew T.; Chang-Claude, Jenny; Chen, Xuechen; Conti, David V.; Dampier, Christopher H.; Devall, Matthew A. M.; Drew, David A.; Figueiredo, Jane C.; Gallinger, Steven; Giles, Graham G.; Gruber, Stephen B.; Gsur, Andrea; Gunter, Marc J.; Harrison, Tabitha A.; Hidaka, Akihisa; Hoffmeister, Michael; Huyghe, Jeroen R.; Jenkins, Mark A.; Jordahl, Kristina M.; Kawaguchi, Eric; Keku, Temitope O.; Kundaje, Anshul; Le Marchand, Loic; Lewinger, Juan Pablo; Li, Li; Mahesworo, Bharuno; Morrison, John L.; Murphy, Neil; Nan, Hongmei; Nassir, Rami; Newcomb, Polly A.; Obón-Santacana, Mireia; Ogino, Shuji; Ose, Jennifer; Pai, Rish K.; Palmer, Julie R.; Papadimitriou, Nikos; Pardamean, Bens; Peoples, Anita R.; Pharoah, Paul D. P.; Platz, Elizabeth A.; Rennert, Gad; Ruiz-Narvaez, Edward; Sakoda, Lori C.; Scacheri, Peter C.; Schmit, Stephanie L.; Schoen, Robert E.; Shcherbina, Anna; Slattery, Martha L.; Stern, Mariana C.; Su, Yu-Ru; Tangen, Catherine M.; Thomas, Duncan C.; Tian, Yu; Tsilidis, Konstantinos K.; Ulrich, Cornelia M.; van Duijnhoven, Fränzel J. B.; Van Guelpen, Bethany; Visvanathan, Kala; Vodicka, Pavel; Wawan Cenggoro, Tjeng; Weinstein, Stephanie J.; White, Emily; Wolk, Alicja; Woods, Michael O.; Hsu, Li; Peters, Ulrike; Moreno, Victor; Gauderman, W. James; Epidemiology, Richard M. Fairbanks School of Public Health
    Background: Tobacco smoking is an established risk factor for colorectal cancer. However, genetically defined population subgroups may have increased susceptibility to smoking-related effects on colorectal cancer. Methods: A genome-wide interaction scan was performed including 33,756 colorectal cancer cases and 44,346 controls from three genetic consortia. Results: Evidence of an interaction was observed between smoking status (ever vs. never smokers) and a locus on 3p12.1 (rs9880919, P = 4.58 × 10-8), with higher associated risk in subjects carrying the GG genotype [OR, 1.25; 95% confidence interval (CI), 1.20-1.30] compared with the other genotypes (OR <1.17 for GA and AA). Among ever smokers, we observed interactions between smoking intensity (increase in 10 cigarettes smoked per day) and two loci on 6p21.33 (rs4151657, P = 1.72 × 10-8) and 8q24.23 (rs7005722, P = 2.88 × 10-8). Subjects carrying the rs4151657 TT genotype showed higher risk (OR, 1.12; 95% CI, 1.09-1.16) compared with the other genotypes (OR <1.06 for TC and CC). Similarly, higher risk was observed among subjects carrying the rs7005722 AA genotype (OR, 1.17; 95% CI, 1.07-1.28) compared with the other genotypes (OR <1.13 for AC and CC). Functional annotation revealed that SNPs in 3p12.1 and 6p21.33 loci were located in regulatory regions, and were associated with expression levels of nearby genes. Genetic models predicting gene expression revealed that smoking parameters were associated with lower colorectal cancer risk with higher expression levels of CADM2 (3p12.1) and ATF6B (6p21.33). Conclusions: Our study identified novel genetic loci that may modulate the risk for colorectal cancer of smoking status and intensity, linked to tumor suppression and immune response. Impact: These findings can guide potential prevention treatments.