المؤلفون: Tian, Yu, Lin, Yi, Qu, Conghui, Arndt, Volker, Baurley, James W., Berndt, Sonja I., Bien, Stephanie A., Bishop, D. Timothy, Brenner, Hermann, Buchanan, Daniel D., Budiarto, Arif, Campbell, Peter T., Carreras-Torres, Robert, Casey, Graham, Chan, Andrew T., Chen, Rui, Chen, Xuechen, Conti, David V., Díez-Obrero, Virginia, Dimou, Niki, Drew, David A., Figueiredo, Jane C., Gallinger, Steven, Giles, Graham G., Gruber, Stephen B., Gunter, Marc J., Harlid, Sophia, 1978, Harrison, Tabitha A., Hidaka, Akihisa, Hoffmeister, Michael, Huyghe, Jeroen R., Jenkins, Mark A., Jordahl, Kristina M., Joshi, Amit D., Keku, Temitope O., Kawaguchi, Eric, Kim, Andre E., Kundaje, Anshul, Larsson, Susanna C., Marchand, Loic Le, Lewinger, Juan Pablo, Li, Li, Moreno, Victor, Morrison, John, Murphy, Neil, Nan, Hongmei, Nassir, Rami, Newcomb, Polly A., Obón-Santacana, Mireia, Ogino, Shuji, Ose, Jennifer, Pardamean, Bens, Pellatt, Andrew J., Peoples, Anita R., Platz, Elizabeth A., Potter, John D., Prentice, Ross L., Rennert, Gad, Ruiz-Narvaez, Edward A., Sakoda, Lori C., Schoen, Robert E., Shcherbina, Anna, Stern, Mariana C., Su, Yu-Ru, Thibodeau, Stephen N., Thomas, Duncan C., Tsilidis, Konstantinos K., van Duijnhoven, Franzel J. B., van Guelpen, Bethany, Visvanathan, Kala, White, Emily, Wolk, Alicja, Woods, Michael O., Wu, Anna H., Peters, Ulrike, Gauderman, W. James, Hsu, Li, Chang-Claude, Jenny

المصدر: British Journal of Cancer. 130(10):1687-1696

الوصف: Background: Menopausal hormone therapy (MHT), a common treatment to relieve symptoms of menopause, is associated with a lower risk of colorectal cancer (CRC). To inform CRC risk prediction and MHT risk-benefit assessment, we aimed to evaluate the joint association of a polygenic risk score (PRS) for CRC and MHT on CRC risk.Methods: We used data from 28,486 postmenopausal women (11,519 cases and 16,967 controls) of European descent. A PRS based on 141 CRC-associated genetic variants was modeled as a categorical variable in quartiles. Multiplicative interaction between PRS and MHT use was evaluated using logistic regression. Additive interaction was measured using the relative excess risk due to interaction (RERI). 30-year cumulative risks of CRC for 50-year-old women according to MHT use and PRS were calculated.Results: The reduction in odds ratios by MHT use was larger in women within the highest quartile of PRS compared to that in women within the lowest quartile of PRS (p-value = 2.7 × 10−8). At the highest quartile of PRS, the 30-year CRC risk was statistically significantly lower for women taking any MHT than for women not taking any MHT, 3.7% (3.3%–4.0%) vs 6.1% (5.7%–6.5%) (difference 2.4%, P-value = 1.83 × 10−14); these differences were also statistically significant but smaller in magnitude in the lowest PRS quartile, 1.6% (1.4%–1.8%) vs 2.2% (1.9%–2.4%) (difference 0.6%, P-value = 1.01 × 10−3), indicating 4 times greater reduction in absolute risk associated with any MHT use in the highest compared to the lowest quartile of genetic CRC risk.Conclusions: MHT use has a greater impact on the reduction of CRC risk for women at higher genetic risk. These findings have implications for the development of risk prediction models for CRC and potentially for the consideration of genetic information in the risk-benefit assessment of MHT use.

وصف الملف: electronic

URL الوصول: https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-223079
https://doi.org/10.1038/s41416-024-02638-2
https://umu.diva-portal.org/smash/get/diva2:1852222/FULLTEXT02.pdf

المؤلفون: Watts, Eleanor L., Gonzales, Tomas I., Strain, Tessa, Saint-Maurice, Pedro F., Bishop, D. Timothy, Chanock, Stephen J., Johansson, Mattias, Keku, Temitope O., Le Marchand, Loic, Moreno, Victor, Newcomb, Polly A., Newton, Christina C., Pai, Rish K., Purdue, Mark P., Ulrich, Cornelia M., Smith-Byrne, Karl, van Guelpen, Bethany, Eeles, Rosalind A., Haiman, Christopher A., Kote-Jarai, Zsofia, Schumacher, Fredrick R., Benlloch, Sara, Olama, Ali Amin Al, Muir, Kenneth R., Berndt, Sonja I., Conti, David V., Wiklund, Fredrik, Wang, Ying, Tangen, Catherine M., Batra, Jyotsna, Clements, Judith A., Grönberg, Henrik, Pashayan, Nora, Schleutker, Johanna, Albanes, Demetrius, Weinstein, Stephanie J., Wolk, Alicja, West, Catharine M. L., Mucci, Lorelei A., Cancel-Tassin, Géraldine, Koutros, Stella, Sørensen, Karina Dalsgaard, Grindedal, Eli Marie, Neal, David E., Hamdy, Freddie C., Donovan, Jenny L., Travis, Ruth C., Hamilton, Robert J., Ingles, Sue Ann, Rosenstein, Barry S., Lu, Yong-Jie, Giles, Graham G., MacInnis, Robert J., Kibel, Adam S., Vega, Ana, Kogevinas, Manolis, Penney, Kathryn L., Park, Jong Y., Stanford, Janet L., Cybulski, Cezary, Nordestgaard, Børge G., Nielsen, Sune F., Brenner, Hermann, Maier, Christiane, Kim, Jeri, John, Esther M., Teixeira, Manuel R., Neuhausen, Susan L., De Ruyck, Kim, Razack, Azad, Newcomb, Lisa F., Lessel, Davor, Kaneva, Radka, Usmani, Nawaid, Claessens, Frank, Townsend, Paul A., Castelao, Jose Esteban, Roobol, Monique J., Menegaux, Florence, Khaw, Kay-Tee, Cannon-Albright, Lisa, Pandha, Hardev, Thibodeau, Stephen N., Hunter, David J., Kraft, Peter, Blot, William J., Riboli, Elio, Day, Felix R., Wijndaele, Katrien, Wareham, Nicholas J., Matthews, Charles E., Moore, Steven C., Brage, Soren

المصدر: British Journal of Cancer. 130:114-124

الوصف: Background: The association of fitness with cancer risk is not clear.Methods: We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of lung, colorectal, endometrial, breast, and prostate cancer in a subset of UK Biobank participants who completed a submaximal fitness test in 2009-12 (N = 72,572). We also investigated relationships using two-sample Mendelian randomisation (MR), odds ratios (ORs) were estimated using the inverse-variance weighted method.Results: After a median of 11 years of follow-up, 4290 cancers of interest were diagnosed. A 3.5 ml O2⋅min−1⋅kg−1 total-body mass increase in fitness (equivalent to 1 metabolic equivalent of task (MET), approximately 0.5 standard deviation (SD)) was associated with lower risks of endometrial (HR = 0.81, 95% CI: 0.73–0.89), colorectal (0.94, 0.90–0.99), and breast cancer (0.96, 0.92–0.99). In MR analyses, a 0.5 SD increase in genetically predicted O2⋅min−1⋅kg−1 fat-free mass was associated with a lower risk of breast cancer (OR = 0.92, 95% CI: 0.86–0.98). After adjusting for adiposity, both the observational and genetic associations were attenuated.Discussion: Higher fitness levels may reduce risks of endometrial, colorectal, and breast cancer, though relationships with adiposity are complex and may mediate these relationships. Increasing fitness, including via changes in body composition, may be an effective strategy for cancer prevention.

وصف الملف: electronic

URL الوصول: https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-218042
https://doi.org/10.1038/s41416-023-02489-3
https://umu.diva-portal.org/smash/get/diva2:1819631/FULLTEXT02.pdf

المؤلفون: Wang, Anqi, Shen, Jiayi, Rodriguez, Alex A., Saunders, Edward J., Chen, Fei, Janivara, Rohini, Darst, Burcu F.^{Aff1, Aff5}, Sheng, Xin, Xu, Yili, Chou, Alisha J., Benlloch, Sara, Dadaev, Tokhir, Brook, Mark N., Plym, Anna^{Aff7, Aff8}, Sahimi, Ali, Hoffman, Thomas J.^{Aff10, Aff11}, Takahashi, Atushi^{Aff12, Aff13}, Matsuda, Koichi, Momozawa, Yukihide, Fujita, Masashi, Laisk, Triin, Figuerêdo, Jéssica, Muir, Kenneth^{Aff18, Aff19}, Ito, Shuji^{Aff20, Aff21}, Liu, Xiaoxi, Uchio, Yuji, Kubo, Michiaki, Kamatani, Yoichiro^{Aff22, Aff23}, Lophatananon, Artitaya, Wan, Peggy, Andrews, Caroline, Lori, Adriana, Choudhury, Parichoy P., Schleutker, Johanna^{Aff27, Aff28}, Tammela, Teuvo L. J., Sipeky, Csilla, Auvinen, Anssi, Giles, Graham G.^{Aff31, Aff32, Aff33}, Southey, Melissa C., MacInnis, Robert J.^{Aff31, Aff32}, Cybulski, Cezary, Wokolorczyk, Dominika, Lubinski, Jan, Rentsch, Christopher T.^{Aff35, Aff36, Aff37}, Cho, Kelly^{Aff38, Aff39}, Mcmahon, Benjamin H., Neal, David E.^{Aff41, Aff42, Aff43}, Donovan, Jenny L., Hamdy, Freddie C.^{Aff45, Aff46}, Martin, Richard M.^{Aff44, Aff47, Aff48}, Nordestgaard, Borge G.^{Aff49, Aff50}, Nielsen, Sune F.^{Aff49, Aff50}, Weischer, Maren, Bojesen, Stig E.^{Aff49, Aff50}, Røder, Andreas^{Aff51, Aff52}, Stroomberg, Hein V., Batra, Jyotsna^{Aff53, Aff54}, Chambers, Suzanne, Horvath, Lisa^{Aff56, Aff57}, Clements, Judith A., Tilly, Wayne, Risbridger, Gail P.^{Aff59, Aff60}, Gronberg, Henrik, Aly, Markus^{Aff7, Aff61, Aff62}, Szulkin, Robert^{Aff7, Aff63}, Eklund, Martin, Nordstrom, Tobias^{Aff7, Aff64}, Pashayan, Nora^{Aff65, Aff66}, Dunning, Alison M., Ghoussaini, Maya, Travis, Ruth C., Key, Tim J., Riboli, Elio, Park, Jong Y., Sellers, Thomas A., Lin, Hui-Yi, Albanes, Demetrius, Weinstein, Stephanie, Cook, Michael B., Mucci, Lorelei A., Giovannucci, Edward, Lindstrom, Sara, Kraft, Peter, Hunter, David J., Penney, Kathryn L., Turman, Constance, Tangen, Catherine M., Goodman, Phyllis J., Thompson, Jr., Ian M., Hamilton, Robert J.^{Aff80, Aff81}, Fleshner, Neil E., Finelli, Antonio, Parent, Marie-Élise, Stanford, Janet L., Ostrander, Elaine A., Koutros, Stella, Beane Freeman, Laura E., Stampfer, Meir, Wolk, Alicja^{Aff85, Aff86}, Håkansson, Niclas, Andriole, Gerald L., Hoover, Robert N., Machiela, Mitchell J., Sørensen, Karina Dalsgaard^{Aff88, Aff89}, Borre, Michael^{Aff89, Aff90}, Blot, William J.^{Aff91, Aff92}, Zheng, Wei, Yeboah, Edward D., Mensah, James E.^{Aff93, Aff94}, Lu, Yong-Jie, Zhang, Hong-Wei, Feng, Ninghan, Mao, Xueying, Wu, Yudong, Zhao, Shan-Chao, Sun, Zan, Thibodeau, Stephen N., McDonnell, Shannon K., Schaid, Daniel J., West, Catharine M. L., Barnett, Gill, Maier, Christiane, Schnoeller, Thomas, Luedeke, Manuel, Kibel, Adam S., Drake, Bettina F., Cussenot, Olivier^{Aff109, Aff110}, Cancel-Tassin, Geraldine^{Aff109, Aff110}, Menegaux, Florence, Truong, Thérèse, Koudou, Yves Akoli, John, Esther M., Grindedal, Eli Marie, Maehle, Lovise, Khaw, Kay-Tee, Ingles, Sue A., Stern, Mariana C., Vega, Ana^{Aff117, Aff118, Aff119}, Gómez-Caamaño, Antonio, Fachal, Laura^{Aff117, Aff118, Aff119, Aff121}, Rosenstein, Barry S.^{Aff122, Aff123}, Kerns, Sarah L., Ostrer, Harry, Teixeira, Manuel R.^{Aff126, Aff127, Aff128}, Paulo, Paula, Brandão, Andreia, Watya, Stephen, Lubwama, Alexander, Bensen, Jeannette T.^{Aff130, Aff131}, Butler, Ebonee N., Mohler, James L.^{Aff131, Aff132}, Taylor, Jack A.^{Aff133, Aff134}, Kogevinas, Manolis^{Aff135, Aff136, Aff137, Aff138}, Dierssen-Sotos, Trinidad^{Aff138, Aff139}, Castaño-Vinyals, Gemma^{Aff135, Aff136, Aff137, Aff138}, Cannon-Albright, Lisa^{Aff140, Aff141}, Teerlink, Craig C.^{Aff140, Aff141}, Huff, Chad D., Pilie, Patrick, Yu, Yao, Bohlender, Ryan J., Gu, Jian, Strom, Sara S., Multigner, Luc, Blanchet, Pascal, Brureau, Laurent, Kaneva, Radka, Slavov, Chavdar, Mitev, Vanio, Leach, Robin J., Brenner, Hermann^{Aff150, Aff151, Aff152}, Chen, Xuechen, Holleczek, Bernd, Schöttker, Ben, Klein, Eric A.^{Aff154, Aff155}, Hsing, Ann W., Kittles, Rick A., Murphy, Adam B., Logothetis, Christopher J., Kim, Jeri, Neuhausen, Susan L., Steele, Linda, Ding, Yuan Chun, Isaacs, William B., Nemesure, Barbara, Hennis, Anselm J. M.^{Aff160, Aff161}, Carpten, John, Pandha, Hardev, Michael, Agnieszka, De Ruyck, Kim, De Meerleer, Gert, Ost, Piet, Xu, Jianfeng, Razack, Azad, Lim, Jasmine, Teo, Soo-Hwang, Newcomb, Lisa F.^{Aff5, Aff169}, Lin, Daniel W.^{Aff5, Aff169}, Fowke, Jay H., Neslund-Dudas, Christine M., Rybicki, Benjamin A., Gamulin, Marija, Lessel, Davor, Kulis, Tomislav, Usmani, Nawaid^{Aff175, Aff176}, Abraham, Aswin^{Aff175, Aff176}, Singhal, Sandeep, Parliament, Matthew^{Aff175, Aff176}, Claessens, Frank, Joniau, Steven, Van den Broeck, Thomas^{Aff177, Aff178}, Gago-Dominguez, Manuela^{Aff179, Aff180}, Castelao, Jose Esteban, Martinez, Maria Elena, Larkin, Samantha, Townsend, Paul A., Aukim-Hastie, Claire, Bush, William S., Aldrich, Melinda C., Crawford, Dana C., Srivastava, Shiv, Cullen, Jennifer^{Aff186, Aff189}, Petrovics, Gyorgy, Casey, Graham, Wang, Ying, Tettey, Yao^{Aff94, Aff191}, Lachance, Joseph, Tang, Wei, Biritwum, Richard B., Adjei, Andrew A., Tay, Evelyn, Truelove, Ann, Niwa, Shelley, Yamoah, Kosj^{Aff70, Aff195}, Govindasami, Koveela, Chokkalingam, Anand P., Keaton, Jacob M.^{Aff91, Aff197}, Hellwege, Jacklyn N.^{Aff91, Aff198}, Clark, Peter E., Jalloh, Mohamed, Gueye, Serigne M., Niang, Lamine, Ogunbiyi, Olufemi, Shittu, Olayiwola, Amodu, Olukemi, Adebiyi, Akindele O., Aisuodionoe-Shadrach, Oseremen I., Ajibola, Hafees O., Jamda, Mustapha A., Oluwole, Olabode P., Nwegbu, Maxwell, Adusei, Ben, Mante, Sunny, Darkwa-Abrahams, Afua, Diop, Halimatou, Gundell, Susan M., Roobol, Monique J., Jenster, Guido, van Schaik, Ron H. N., Hu, Jennifer J., Sanderson, Maureen, Kachuri, Linda, Varma, Rohit, McKean-Cowdin, Roberta, Torres, Mina, Preuss, Michael H., Loos, Ruth J. F., Zawistowski, Matthew^{Aff215, Aff216}, Zöllner, Sebastian^{Aff215, Aff216, Aff217}, Lu, Zeyun, Van Den Eeden, Stephen K., Easton, Douglas F., Ambs, Stefan, Edwards, Todd L., Mägi, Reedik, Rebbeck, Timothy R., Fritsche, Lars, Chanock, Stephen J., Berndt, Sonja I., Wiklund, Fredrik, Nakagawa, Hidewaki, Witte, John S.^{Aff212, Aff220}, Gaziano, J. Michael^{Aff38, Aff39}, Justice, Amy C., Mancuso, Nick, Terao, Chikashi^{Aff22, Aff221, Aff222}, Eeles, Rosalind A.^{Aff3, Aff223}, Kote-Jarai, Zsofia, Madduri, Ravi K., Conti, David V., Haiman, Christopher A.^{Aff1, IDs41588023015344_cor292}

المصدر: Nature Genetics. 55(12):2065-2074

المؤلفون: Papadimitriou, Nikos, Qu, Conghui, Harrison, Tabitha A., Bever, Alaina M., Martin, Richard M., Tsilidis, Konstantinos K., Newcomb, Polly A., Thibodeau, Stephen N., Newton, Christina C., Um, Caroline Y., Obón-Santacana, Mireia, Moreno, Victor, Brenner, Hermann, Mandic, Marko, Chang-Claude, Jenny, Hoffmeister, Michael, Pellatt, Andrew J., Schoen, Robert E., Harlid, Sophia, 1978, Ogino, Shuji, Ugai, Tomotaka, Buchanan, Daniel D., Lynch, Brigid M., Gruber, Stephen B., Cao, Yin, Hsu, Li, Huyghe, Jeroen R., Lin, Yi, Steinfelder, Robert S., Sun, Wei, van Guelpen, Bethany, Zaidi, Syed H., Toland, Amanda E., Berndt, Sonja I., Huang, Wen-Yi, Aglago, Elom K., Drew, David A., French, Amy J., Georgeson, Peter, Giannakis, Marios, Hullar, Meredith, Nowak, Johnathan A., Thomas, Claire E., Le Marchand, Loic, Cheng, Iona, Gallinger, Steven, Jenkins, Mark A., Gunter, Marc J., Campbell, Peter T., Peters, Ulrike, Song, Mingyang, Phipps, Amanda I., Murphy, Neil

المصدر: EBioMedicine. 101

مصطلحات موضوعية: Colorectal cancer, Mendelian randomization, Molecular subtypes, Obesity

الوصف: Background: Obesity has been positively associated with most molecular subtypes of colorectal cancer (CRC); however, the magnitude and the causality of these associations is uncertain.Methods: We used Mendelian randomization (MR) to examine potential causal relationships between body size traits (body mass index [BMI], waist circumference, and body fat percentage) with risks of Jass classification types and individual subtypes of CRC (microsatellite instability [MSI] status, CpG island methylator phenotype [CIMP] status, BRAF and KRAS mutations). Summary data on tumour markers were obtained from two genetic consortia (CCFR, GECCO).Findings: A 1-standard deviation (SD:5.1 kg/m2) increment in BMI levels was found to increase risks of Jass type 1MSI-high,CIMP-high,BRAF-mutated,KRAS-wildtype (odds ratio [OR]: 2.14, 95% confidence interval [CI]: 1.46, 3.13; p-value = 9 × 10−5) and Jass type 2non-MSI-high,CIMP-high,BRAF-mutated,KRAS-wildtype CRC (OR: 2.20, 95% CI: 1.26, 3.86; p-value = 0.005). The magnitude of these associations was stronger compared with Jass type 4non-MSI-high,CIMP-low/negative,BRAF-wildtype,KRAS-wildtype CRC (p-differences: 0.03 and 0.04, respectively). A 1-SD (SD:13.4 cm) increment in waist circumference increased risk of Jass type 3non-MSI-high,CIMP-low/negative,BRAF-wildtype,KRAS-mutated (OR 1.73, 95% CI: 1.34, 2.25; p-value = 9 × 10−5) that was stronger compared with Jass type 4 CRC (p-difference: 0.03). A higher body fat percentage (SD:8.5%) increased risk of Jass type 1 CRC (OR: 2.59, 95% CI: 1.49, 4.48; p-value = 0.001), which was greater than Jass type 4 CRC (p-difference: 0.03).Interpretation: Body size was more strongly linked to the serrated (Jass types 1 and 2) and alternate (Jass type 3) pathways of colorectal carcinogenesis in comparison to the traditional pathway (Jass type 4).Funding: Cancer Research UK, National Institute for Health Research, Medical Research Council, National Institutes of Health, National Cancer Institute, American Institute for Cancer Research, Brigham and Women's Hospital, Prevent Cancer Foundation, Victorian Cancer Agency, Swedish Research Council, Swedish Cancer Society, Region Västerbotten, Knut and Alice Wallenberg Foundation, Lion's Cancer Research Foundation, Insamlingsstiftelsen, Umeå University. Full funding details are provided in acknowledgements.

وصف الملف: electronic

URL الوصول: https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-222809
https://doi.org/10.1016/j.ebiom.2024.105010
https://umu.diva-portal.org/smash/get/diva2:1850826/FULLTEXT01.pdf

المؤلفون: Aglago, Elom K., Kim, Andre, Lin, Yi, Qu, Conghui, Evangelou, Marina, Ren, Yu, Morrison, John, Albanes, Demetrius, Arndt, Volker, Barry, Elizabeth L., Baurley, James W., Berndt, Sonja I., Bien, Stephanie A., Bishop, D Timothy, Bouras, Emmanouil, Brenner, Hermann, Buchanan, Daniel D., Budiarto, Arif, Carreras-Torres, Robert, Casey, Graham, Cenggoro, Tjeng Wawan, Chan, Andrew T., Chang-Claude, Jenny, Chen, Xuechen, Conti, David V., Devall, Matthew, Diez-Obrero, Virginia, Dimou, Niki, Drew, David, Figueiredo, Jane C., Gallinger, Steven, Giles, Graham G., Gruber, Stephen B., Gsur, Andrea, Gunter, Marc J., Hampel, Heather, Harlid, Sophia, 1978, Hidaka, Akihisa, Harrison, Tabitha A., Hoffmeister, Michael, Huyghe, Jeroen R., Jenkins, Mark A., Jordahl, Kristina, Joshi, Amit D., Kawaguchi, Eric S., Keku, Temitope O., Kundaje, Anshul, Larsson, Susanna C., Marchand, Loic Le, Lewinger, Juan Pablo, Li, Li, Lynch, Brigid M., Mahesworo, Bharuno, Mandic, Marko, Obón-Santacana, Mireia, Moreno, Victor, Murphy, Neil, Nan, Hongmei, Nassir, Rami, Newcomb, Polly A., Ogino, Shuji, Ose, Jennifer, Pai, Rish K., Palmer, Julie R., Papadimitriou, Nikos, Pardamean, Bens, Peoples, Anita R., Platz, Elizabeth A., Potter, John D., Prentice, Ross L., 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., Thibodeau, Stephen N., Thomas, Duncan C., Tian, Yu, Ulrich, Cornelia M., van Duijnhoven, Franzel Jb, van Guelpen, Bethany, Visvanathan, Kala, Vodicka, Pavel, Wang, Jun, White, Emily, Wolk, Alicja, Woods, Michael O., Wu, Anna H., Zemlianskaia, Natalia, Hsu, Li, Gauderman, W James, Peters, Ulrike, Tsilidis, Konstantinos K., Campbell, Peter T.

المصدر: Cancer Research. 83(15):2572-2583

الوصف: Colorectal cancer risk can be impacted by genetic, environmental, and lifestyle factors, including diet and obesity. Gene-environment interactions (G × E) can provide biological insights into the effects of obesity on colorectal cancer risk. Here, we assessed potential genome-wide G × E interactions between body mass index (BMI) and common SNPs for colorectal cancer risk using data from 36,415 colorectal cancer cases and 48,451 controls from three international colorectal cancer consortia (CCFR, CORECT, and GECCO). The G × E tests included the conventional logistic regression using multiplicative terms (one degree of freedom, 1DF test), the two-step EDGE method, and the joint 3DF test, each of which is powerful for detecting G × E interactions under specific conditions. BMI was associated with higher colorectal cancer risk. The two-step approach revealed a statistically significant G×BMI interaction located within the Formin 1/Gremlin 1 (FMN1/GREM1) gene region (rs58349661). This SNP was also identified by the 3DF test, with a suggestive statistical significance in the 1DF test. Among participants with the CC genotype of rs58349661, overweight and obesity categories were associated with higher colorectal cancer risk, whereas null associations were observed across BMI categories in those with the TT genotype. Using data from three large international consortia, this study discovered a locus in the FMN1/GREM1 gene region that interacts with BMI on the association with colorectal cancer risk. Further studies should examine the potential mechanisms through which this locus modifies the etiologic link between obesity and colorectal cancer.SIGNIFICANCE: This gene-environment interaction analysis revealed a genetic locus in FMN1/GREM1 that interacts with body mass index in colorectal cancer risk, suggesting potential implications for precision prevention strategies.

وصف الملف: electronic

URL الوصول: https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-212758
https://doi.org/10.1158/0008-5472.CAN-22-3713
https://umu.diva-portal.org/smash/get/diva2:1787028/FULLTEXT01.pdf

المؤلفون: Dimou, Niki^{Aff1, IDs4141602302312z_cor1}, Kim, Andre E., Flanagan, Orlagh, Murphy, Neil, Diez-Obrero, Virginia^{Aff3, Aff4, Aff5, Aff6}, Shcherbina, Anna^{Aff7, Aff8}, Aglago, Elom K., Bouras, Emmanouil, Campbell, Peter T., Casey, Graham, Gallinger, Steven, Gruber, Stephen B., Jenkins, Mark A., Lin, Yi, Moreno, Victor^{Aff6, Aff17, Aff18, Aff19}, Ruiz-Narvaez, Edward, Stern, Mariana C., Tian, Yu^{Aff22, Aff23}, Tsilidis, Kostas K.^{Aff9, Aff10}, Arndt, Volker, Barry, Elizabeth L., Baurley, James W.^{Aff26, Aff27}, Berndt, Sonja I., Bézieau, Stéphane, Bien, Stephanie A., Bishop, D. Timothy, Brenner, Hermann^{Aff24, Aff31, Aff32}, Budiarto, Arif^{Aff26, Aff33}, Carreras-Torres, Robert, Cenggoro, Tjeng Wawan, Chan, Andrew T.^{Aff35, Aff36, Aff37, Aff38, Aff39, Aff40}, Chang-Claude, Jenny^{Aff22, Aff41}, Chanock, Stephen J., Chen, Xuechen^{Aff24, Aff42}, Conti, David V., Dampier, Christopher H.^{Aff12, Aff43}, Devall, Matthew, Drew, David A., Figueiredo, Jane C., Giles, Graham G.^{Aff15, Aff47, Aff48}, Gsur, Andrea, Harrison, Tabitha A., Hidaka, Akihisa, Hoffmeister, Michael, Huyghe, Jeroen R., Jordahl, Kristina, Kawaguchi, Eric, Keku, Temitope O., Larsson, Susanna C., Le Marchand, Loic, Lewinger, Juan Pablo, Li, Li, Mahesworo, Bharuno, Morrison, John, Newcomb, Polly A.^{Aff16, Aff53}, Newton, Christina C., Obon-Santacana, Mireia, Ose, Jennifer^{Aff56, Aff57}, Pai, Rish K., Palmer, Julie R., Papadimitriou, Nikos, Pardamean, Bens, Peoples, Anita R.^{Aff56, Aff57}, Pharoah, Paul D. P., Platz, Elizabeth A., Potter, John D.^{Aff16, Aff62, Aff63}, Rennert, Gad^{Aff64, Aff65, Aff66}, Scacheri, Peter C., Schoen, Robert E., Su, Yu-Ru, Tangen, Catherine M., Thibodeau, Stephen N., Thomas, Duncan C., Ulrich, Cornelia M.^{Aff56, Aff57}, Um, Caroline Y., van Duijnhoven, Franzel J. B., Visvanathan, Kala, Vodicka, Pavel^{Aff73, Aff74, Aff75}, Vodickova, Ludmila^{Aff73, Aff74, Aff75}, White, Emily^{Aff16, Aff62}, Wolk, Alicja, Woods, Michael O., Qu, Conghui, Kundaje, Anshul^{Aff7, Aff8}, Hsu, Li^{Aff16, Aff77}, Gauderman, W. James, Gunter, Marc J.^{Aff1, Aff9}, Peters, Ulrike^{Aff16, Aff62}

المصدر: British Journal of Cancer. 129(3):511-520

المؤلفون: Tian, Yu, Kim, Andre E, Bien, Stephanie A, Lin, Yi, Qu, Conghui, Harrison, Tabitha A, Carreras-Torres, Robert, Díez-Obrero, Virginia, Dimou, Niki, Drew, David A, Hidaka, Akihisa, Huyghe, Jeroen R, Jordahl, Kristina M, Morrison, John, Murphy, Neil, Obón-Santacana, Mireia, Ulrich, Cornelia M, Ose, Jennifer, Peoples, Anita R, Ruiz-Narvaez, Edward A, Shcherbina, Anna, Stern, Mariana C, Su, Yu-Ru, van Duijnhoven, Franzel JB, Arndt, Volker, Baurley, James W, Berndt, Sonja I, Bishop, D Timothy, Brenner, Hermann, Buchanan, Daniel D, Chan, Andrew T, Figueiredo, Jane C, Gallinger, Steven, Gruber, Stephen B, Harlid, Sophia, Hoffmeister, Michael, Jenkins, Mark A, Joshi, Amit D, Keku, Temitope O, Larsson, Susanna C, Le Marchand, Loic, Li, Li, Giles, Graham G, Milne, Roger L, Nan, Hongmei, Nassir, Rami, Ogino, Shuji, Budiarto, Arif, Platz, Elizabeth A, Potter, John D, Prentice, Ross L, Rennert, Gad, Sakoda, Lori C, Schoen, Robert E, Slattery, Martha L, Thibodeau, Stephen N, Van Guelpen, Bethany, Visvanathan, Kala, White, Emily, Wolk, Alicja, Woods, Michael O, Wu, Anna H, Campbell, Peter T, Casey, Graham, Conti, David V, Gunter, Marc J, Kundaje, Anshul, Lewinger, Juan Pablo, Moreno, Victor, Newcomb, Polly A, Pardamean, Bens, Thomas, Duncan C, Tsilidis, Konstantinos K, Peters, Ulrike, Gauderman, W James, Hsu, Li, Chang-Claude, Jenny

المصدر: Journal of the National Cancer Institute. 114(8)

مصطلحات موضوعية: Humans, Colorectal Neoplasms, Estrogens, Progestins, Risk Factors, Case-Control Studies, Menopause, Polymorphism, Single Nucleotide, Female, Aging, Digestive Diseases, Estrogen, Colo-Rectal Cancer, Genetics, Prevention, Human Genome, Clinical Research, Cancer, 2.1 Biological and endogenous factors, Aetiology, Oncology and Carcinogenesis, Oncology & Carcinogenesis

الوصف: BackgroundThe use of menopausal hormone therapy (MHT) may interact with genetic variants to influence colorectal cancer (CRC) risk.MethodsWe conducted a genome-wide, gene-environment interaction between single nucleotide polymorphisms and the use of any MHT, estrogen only, and combined estrogen-progestogen therapy with CRC risk, among 28 486 postmenopausal women (11 519 CRC patients and 16 967 participants without CRC) from 38 studies, using logistic regression, 2-step method, and 2- or 3-degree-of-freedom joint test. A set-based score test was applied for rare genetic variants.ResultsThe use of any MHT, estrogen only and estrogen-progestogen were associated with a reduced CRC risk (odds ratio [OR] = 0.71, 95% confidence interval [CI] = 0.64 to 0.78; OR = 0.65, 95% CI = 0.53 to 0.79; and OR = 0.73, 95% CI = 0.59 to 0.90, respectively). The 2-step method identified a statistically significant interaction between a GRIN2B variant rs117868593 and MHT use, whereby MHT-associated CRC risk was statistically significantly reduced in women with the GG genotype (OR = 0.68, 95% CI = 0.64 to 0.72) but not within strata of GC or CC genotypes. A statistically significant interaction between a DCBLD1 intronic variant at 6q22.1 (rs10782186) and MHT use was identified by the 2-degree-of-freedom joint test. The MHT-associated CRC risk was reduced with increasing number of rs10782186-C alleles, showing odds ratios of 0.78 (95% CI = 0.70 to 0.87) for TT, 0.68 (95% CI = 0.63 to 0.73) for TC, and 0.66 (95% CI = 0.60 to 0.74) for CC genotypes. In addition, 5 genes in rare variant analysis showed suggestive interactions with MHT (2-sided P

وصف الملف: application/pdf

URL الوصول: https://escholarship.org/uc/item/3vq0n596

المؤلفون: Althoff, Keri N, Schlueter, David J, Anton-Culver, Hoda, Cherry, James, Denny, Joshua C, Thomsen, Isaac, Karlson, Elizabeth W, Havers, Fiona P, Cicek, Mine S, Thibodeau, Stephen N, Pinto, Ligia A, Lowy, Douglas, Malin, Bradley A, Ohno-Machado, Lucila, Williams, Carolyn, Goldstein, David, Kouame, Aymone, Ramirez, Andrea, Roman, Adrienne, Sharpless, Norman E, Gebo, Kelly A, Schully, Sheri D, Program, on behalf of the All of Us Research

المصدر: Clinical Infectious Diseases. 74(4)

مصطلحات موضوعية: Infectious Diseases, Emerging Infectious Diseases, Lung, Vaccine Related, Biodefense, Clinical Research, Prevention, Good Health and Well Being, Antibodies, Viral, COVID-19, Enzyme-Linked Immunosorbent Assay, Humans, Immunoglobulin G, Population Health, SARS-CoV-2, Sensitivity and Specificity, United States, Epidemic, Immunoglobulin G antibodies, All of Us Research Program, All of Us Research Program, Biological Sciences, Medical and Health Sciences, Microbiology

الوصف: BackgroundWith limited severe acute respiratory syndrome coronavirus (SARS-CoV-2) testing capacity in the United States at the start of the epidemic (January-March 2020), testing was focused on symptomatic patients with a travel history throughout February, obscuring the picture of SARS-CoV-2 seeding and community transmission. We sought to identify individuals with SARS-CoV-2 antibodies in the early weeks of the US epidemic.MethodsAll of Us study participants in all 50 US states provided blood specimens during study visits from 2 January to 18 March 2020. Participants were considered seropositive if they tested positive for SARS-CoV-2 immunoglobulin G (IgG) antibodies with the Abbott Architect SARS-CoV-2 IgG enzyme-linked immunosorbent assay (ELISA) and the EUROIMMUN SARS-CoV-2 ELISA in a sequential testing algorithm. The sensitivity and specificity of these ELISAs and the net sensitivity and specificity of the sequential testing algorithm were estimated, along with 95% confidence intervals (CIs).ResultsThe estimated sensitivities of the Abbott and EUROIMMUN assays were 100% (107 of 107 [95% CI: 96.6%-100%]) and 90.7% (97 of 107 [83.5%-95.4%]), respectively, and the estimated specificities were 99.5% (995 of 1000 [98.8%-99.8%]) and 99.7% (997 of 1000 [99.1%-99.9%]), respectively. The net sensitivity and specificity of our sequential testing algorithm were 90.7% (97 of 107 [95% CI: 83.5%-95.4%]) and 100.0% (1000 of 1000 [99.6%-100%]), respectively. Of the 24 079 study participants with blood specimens from 2 January to 18 March 2020, 9 were seropositive, 7 before the first confirmed case in the states of Illinois, Massachusetts, Wisconsin, Pennsylvania, and Mississippi.ConclusionsOur findings identified SARS-CoV-2 infections weeks before the first recognized cases in 5 US states.

وصف الملف: application/pdf

URL الوصول: https://escholarship.org/uc/item/6262z770

المؤلفون: Landi, Maria Teresa, Stevens, Victoria, Wang, Ying, Albanes, Demetrios, Caporaso, Neil, Brennan, Paul, Amos, Christopher I., Shete, Sanjay, Hung, Rayjean J., Bickeböller, Heike, Risch, Angela, Houlston, Richard, Lam, Stephen, Tardon, Adonina, Chen, Chu, Bojesen, Stig E., Johansson, Mattias, Wichmann, H-Erich, Christiani, David, Rennert, Gadi, Arnold, Susanne, Field, John K., Le Marchand, Loic, Melander, Olle, Brunnström, Hans, Liu, Geoffrey, Andrew, Angeline, Kiemeney, Lambertus A., Shen, Hongbing, Zienolddiny, Shan, Grankvist, Kjell, Johansson, Mikael, Teare, M. Dawn, Hong, Yun-Chul, Yuan, Jian-Min, Lazarus, Philip, Schabath, Matthew B., Aldrich, Melinda C., Eeles, Rosalind A., Haiman, Christopher A., Kote-Jarai, Zsofia, Schumacher, Fredrick R., Benlloch, Sara, Al Olama, Ali Amin, Muir, Kenneth R., Berndt, Sonja I., Conti, David V., Wiklund, Fredrik, Chanock, Stephen, Tangen, Catherine M., Batra, Jyotsna, Clements, Judith A., Grönberg, Henrik, Pashayan, Nora, Schleutker, Johanna, Albanes, Demetrius, Weinstein, Stephanie J., Wolk, Alicja, West, Catharine M.L., Mucci, Lorelei A., Cancel-Tassin, Géraldine, Koutros, Stella, Sørensen, Karina Dalsgaard, Grindedal, Eli Marie, Neal, David E., Hamdy, Freddie C., Donovan, Jenny L., Travis, Ruth C., Hamilton, Robert J., Ingles, Sue Ann, Rosenstein, Barry S., Lu, Yong-Jie, Giles, Graham G., MacInnis, Robert J., Kibel, Adam S., Vega, Ana, Kogevinas, Manolis, Penney, Kathryn L., Park, Jong Y., Stanfrod, Janet L., Cybulski, Cezary, Nordestgaard, Børge G., Nielsen, Sune F., Brenner, Hermann, Maier, Christiane, Logothetis, Christopher J., John, Esther M., Teixeira, Manuel R., Neuhausen, Susan L., De Ruyck, Kim, Razack, Azad, Newcomb, Lisa F., Lessel, Davor, Kaneva, Radka, Usmani, Nawaid, Claessens, Frank, Townsend, Paul A., Castelao, Jose Esteban, Roobol, Monique J., Menegaux, Florence, Khaw, Kay-Tee, Cannon-Albright, Lisa, Pandha, Hardev, Thibodeau, Stephen N., Hunter, David J., Kraft, Peter, Blot, William J., Riboli, Elio, Yarmolinsky, James, Robinson, Jamie W., Mariosa, Daniela, Karhunen, Ville, Huang, Jian, Dimou, Niki, Murphy, Neil, Burrows, Kimberley, Bouras, Emmanouil, Smith-Byrne, Karl, Lewis, Sarah J., Galesloot, Tessel E., Vermeulen, Sita, Martin, Paul, Hou, Lifang, Newcomb, Polly A., White, Emily, Wu, Anna H., Le Marchand, Loïc, Phipps, Amanda I., Buchanan, Daniel D., Zhao, Sizheng Steven, Gill, Dipender, Chanock, Stephen J., Purdue, Mark P., Davey Smith, George, Herzig, Karl-Heinz, Järvelin, Marjo-Riitta, Amos, Chris I., Dehghan, Abbas, Gunter, Marc J., Tsilidis, Kostas K., Martin, Richard M.

المصدر: In eBioMedicine February 2024 100

المؤلفون: Harlid, Sophia, 1978, van Guelpen, Bethany, Qu, Conghui, Gylling, Björn, 1978, Aglago, Elom K., Amitay, Efrat L., Brenner, Hermann, Buchanan, Daniel D., Campbell, Peter T., Cao, Yin, Chan, Andrew T., Chang-Claude, Jenny, Drew, David A., Figueiredo, Jane C., French, Amy J., Gallinger, Steven, Giannakis, Marios, Giles, Graham G., Gunter, Marc J., Hoffmeister, Michael, Hsu, Li, Jenkins, Mark A., Lin, Yi, Moreno, Victor, Murphy, Neil, Newcomb, Polly A., Newton, Christina C., Nowak, Jonathan A., Obón-Santacana, Mireia, Ogino, Shuji, Potter, John D., Song, Mingyang, Steinfelder, Robert S., Sun, Wei, Thibodeau, Stephen N., Toland, Amanda E., Ugai, Tomotaka, Um, Caroline Y., Woods, Michael O., Phipps, Amanda I., Harrison, Tabitha, Peters, Ulrike

المصدر: International Journal of Cancer. 151(3):348-360

مصطلحات موضوعية: Colorectal Cancer, Diabetes, Subtype

الوصف: Diabetes is an established risk factor for colorectal cancer. However, colorectal cancer is a heterogeneous disease and it is not well understood whether diabetes is more strongly associated with some tumor molecular subtypes than others. A better understanding of the association between diabetes and colorectal cancer according to molecular subtypes could provide important insights into the biology of this association. We used data on lifestyle and clinical characteristics from the Colorectal Cancer Family Registry (CCFR) and the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), including 9756 colorectal cancer cases (with tumor marker data) and 9985 controls, to evaluate associations between reported diabetes and risk of colorectal cancer according to molecular subtypes. Tumor markers included BRAF and KRAS mutations, microsatellite instability and CpG island methylator phenotype. In the multinomial logistic regression model, comparing colorectal cancer cases to cancer-free controls, diabetes was positively associated with colorectal cancer regardless of subtype. The highest OR estimate was found for BRAF-mutated colorectal cancer, n = 1086 (ORfully adj: 1.67, 95% confidence intervals [CI]: 1.36-2.05), with an attenuated association observed between diabetes and colorectal cancer without BRAF-mutations, n = 7959 (ORfully adj: 1.33, 95% CI: 1.19-1.48). In the case only analysis, BRAF-mutation was differentially associated with diabetes (Pdifference = .03). For the other markers, associations with diabetes were similar across tumor subtypes. In conclusion, our study confirms the established association between diabetes and colorectal cancer risk, and suggests that it particularly increases the risk of BRAF-mutated tumors.

وصف الملف: electronic

URL الوصول: https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-193631
https://doi.org/10.1002/ijc.34015
https://umu.diva-portal.org/smash/get/diva2:1650716/FULLTEXT01.pdf