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44 results on '"Amitay, Efrat L."'

2. Prognostic role of detailed colorectal location and tumor molecular features: analyses of 13,101 colorectal cancer patients including 2994 early-onset cases

Author

Ugai, Tomotaka, Akimoto, Naohiko, Haruki, Koichiro, Harrison, Tabitha A., Cao, Yin, Qu, Conghui, Chan, Andrew T., Campbell, Peter T., Berndt, Sonja I., Buchanan, Daniel D., Cross, Amanda J., Diergaarde, Brenda, Gallinger, Steven J., Gunter, Marc J., Harlid, Sophia, Hidaka, Akihisa, Hoffmeister, Michael, Brenner, Hermann, Chang-Claude, Jenny, Hsu, Li, Jenkins, Mark A., Lin, Yi, Milne, Roger L., Moreno, Victor, Newcomb, Polly A., Nishihara, Reiko, Obon-Santacana, Mireia, Pai, Rish K., Sakoda, Lori C., Schoen, Robert E., Slattery, Martha L., Sun, Wei, Amitay, Efrat L., Alwers, Elizabeth, Thibodeau, Stephen N., Toland, Amanda E., Van Guelpen, Bethany, Zaidi, Syed H., Potter, John D., Meyerhardt, Jeffrey A., Giannakis, Marios, Song, Mingyang, Nowak, Jonathan A., Peters, Ulrike, Phipps, Amanda I., and Ogino, Shuji

Published
2023
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3. Landscape of somatic single nucleotide variants and indels in colorectal cancer and impact on survival.

Author

Zaidi, Syed H, Harrison, Tabitha A, Phipps, Amanda I, Steinfelder, Robert, Trinh, Quang M, Qu, Conghui, Banbury, Barbara L, Georgeson, Peter, Grasso, Catherine S, Giannakis, Marios, Adams, Jeremy B, Alwers, Elizabeth, Amitay, Efrat L, Barfield, Richard T, Berndt, Sonja I, Borozan, Ivan, Brenner, Hermann, Brezina, Stefanie, Buchanan, Daniel D, Cao, Yin, Chan, Andrew T, Chang-Claude, Jenny, Connolly, Charles M, Drew, David A, Farris, Alton Brad, Figueiredo, Jane C, French, Amy J, Fuchs, Charles S, Garraway, Levi A, Gruber, Steve, Guinter, Mark A, Hamilton, Stanley R, Harlid, Sophia, Heisler, Lawrence E, Hidaka, Akihisa, Hopper, John L, Huang, Wen-Yi, Huyghe, Jeroen R, Jenkins, Mark A, Krzyzanowski, Paul M, Lemire, Mathieu, Lin, Yi, Luo, Xuemei, Mardis, Elaine R, McPherson, John D, Miller, Jessica K, Moreno, Victor, Mu, Xinmeng Jasmine, Nishihara, Reiko, Papadopoulos, Nickolas, Pasternack, Danielle, Quist, Michael J, Rafikova, Adilya, Reid, Emma EG, Shinbrot, Eve, Shirts, Brian H, Stein, Lincoln D, Teney, Cherie D, Timms, Lee, Um, Caroline Y, Van Guelpen, Bethany, Van Tassel, Megan, Wang, Xiaolong, Wheeler, David A, Yung, Christina K, Hsu, Li, Ogino, Shuji, Gsur, Andrea, Newcomb, Polly A, Gallinger, Steven, Hoffmeister, Michael, Campbell, Peter T, Thibodeau, Stephen N, Sun, Wei, Hudson, Thomas J, and Peters, Ulrike

Abstract

Colorectal cancer (CRC) is a biologically heterogeneous disease. To characterize its mutational profile, we conduct targeted sequencing of 205 genes for 2,105 CRC cases with survival data. Our data shows several findings in addition to enhancing the existing knowledge of CRC. We identify PRKCI, SPZ1, MUTYH, MAP2K4, FETUB, and TGFBR2 as additional genes significantly mutated in CRC. We find that among hypermutated tumors, an increased mutation burden is associated with improved CRC-specific survival (HR = 0.42, 95% CI: 0.21-0.82). Mutations in TP53 are associated with poorer CRC-specific survival, which is most pronounced in cases carrying TP53 mutations with predicted 0% transcriptional activity (HR = 1.53, 95% CI: 1.21-1.94). Furthermore, we observe differences in mutational frequency of several genes and pathways by tumor location, stage, and sex. Overall, this large study provides deep insights into somatic mutations in CRC, and their potential relationships with survival and tumor features.

Published
2020

4. Identifying colorectal cancer caused by biallelic MUTYH pathogenic variants using tumor mutational signatures

Author

Georgeson, Peter, Harrison, Tabitha A., Pope, Bernard J., Zaidi, Syed H., Qu, Conghui, Steinfelder, Robert S., Lin, Yi, Joo, Jihoon E., Mahmood, Khalid, Clendenning, Mark, Walker, Romy, Amitay, Efrat L., Berndt, Sonja I., Brenner, Hermann, Campbell, Peter T., Cao, Yin, Chan, Andrew T., Chang-Claude, Jenny, Doheny, Kimberly F., Drew, David A., Figueiredo, Jane C., French, Amy J., Gallinger, Steven, Giannakis, Marios, Giles, Graham G., Gsur, Andrea, Gunter, Marc J., Hoffmeister, Michael, Hsu, Li, Huang, Wen-Yi, Limburg, Paul, Manson, JoAnn E., Moreno, Victor, Nassir, Rami, Nowak, Jonathan A., Obón-Santacana, Mireia, Ogino, Shuji, Phipps, Amanda I., Potter, John D., Schoen, Robert E., Sun, Wei, Toland, Amanda E., Trinh, Quang M., Ugai, Tomotaka, Macrae, Finlay A., Rosty, Christophe, Hudson, Thomas J., Jenkins, Mark A., Thibodeau, Stephen N., Winship, Ingrid M., Peters, Ulrike, and Buchanan, Daniel D.

Published
2022
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10. Supplementary Table S7 from Intake of Dietary Fruit, Vegetables, and Fiber and Risk of Colorectal Cancer According to Molecular Subtypes: A Pooled Analysis of 9 Studies

Author

Hidaka, Akihisa, primary, Harrison, Tabitha A., primary, Cao, Yin, primary, Sakoda, Lori C., primary, Barfield, Richard, primary, Giannakis, Marios, primary, Song, Mingyang, primary, Phipps, Amanda I., primary, Figueiredo, Jane C., primary, Zaidi, Syed H., primary, Toland, Amanda E., primary, Amitay, Efrat L., primary, Berndt, Sonja I., primary, Borozan, Ivan, primary, Chan, Andrew T., primary, Gallinger, Steven, primary, Gunter, Marc J., primary, Guinter, Mark A., primary, Harlid, Sophia, primary, Hampel, Heather, primary, Jenkins, Mark A., primary, Lin, Yi, primary, Moreno, Victor, primary, Newcomb, Polly A., primary, Nishihara, Reiko, primary, Ogino, Shuji, primary, Obón-Santacana, Mireia, primary, Parfrey, Patrick S., primary, Potter, John D., primary, Slattery, Martha L., primary, Steinfelder, Robert S., primary, Um, Caroline Y., primary, Wang, Xiaoliang, primary, Woods, Michael O., primary, Van Guelpen, Bethany, primary, Thibodeau, Stephen N., primary, Hoffmeister, Michael, primary, Sun, Wei, primary, Hsu, Li, primary, Buchanan, Daniel D., primary, Campbell, Peter T., primary, and Peters, Ulrike, primary

Published
2023
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11. Supplementary Text from Intake of Dietary Fruit, Vegetables, and Fiber and Risk of Colorectal Cancer According to Molecular Subtypes: A Pooled Analysis of 9 Studies

Author

Hidaka, Akihisa, primary, Harrison, Tabitha A., primary, Cao, Yin, primary, Sakoda, Lori C., primary, Barfield, Richard, primary, Giannakis, Marios, primary, Song, Mingyang, primary, Phipps, Amanda I., primary, Figueiredo, Jane C., primary, Zaidi, Syed H., primary, Toland, Amanda E., primary, Amitay, Efrat L., primary, Berndt, Sonja I., primary, Borozan, Ivan, primary, Chan, Andrew T., primary, Gallinger, Steven, primary, Gunter, Marc J., primary, Guinter, Mark A., primary, Harlid, Sophia, primary, Hampel, Heather, primary, Jenkins, Mark A., primary, Lin, Yi, primary, Moreno, Victor, primary, Newcomb, Polly A., primary, Nishihara, Reiko, primary, Ogino, Shuji, primary, Obón-Santacana, Mireia, primary, Parfrey, Patrick S., primary, Potter, John D., primary, Slattery, Martha L., primary, Steinfelder, Robert S., primary, Um, Caroline Y., primary, Wang, Xiaoliang, primary, Woods, Michael O., primary, Van Guelpen, Bethany, primary, Thibodeau, Stephen N., primary, Hoffmeister, Michael, primary, Sun, Wei, primary, Hsu, Li, primary, Buchanan, Daniel D., primary, Campbell, Peter T., primary, and Peters, Ulrike, primary

Published
2023
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12. Molecular characteristics of early-onset colorectal cancer according to detailed anatomical locations : comparison with later-onset cases

Author

Ugai, Tomotaka, Haruki, Koichiro, Harrison, Tabitha A., Cao, Yin, Qu, Conghui, Chan, Andrew T., Campbell, Peter T., Akimoto, Naohiko, Berndt, Sonja, Brenner, Hermann, Buchanan, Daniel D., Chang-Claude, Jenny, Fujiyoshi, Kenji, Gallinger, Steven J., Gunter, Marc J., Hidaka, Akihisa, Hoffmeister, Michael, Hsu, Li, Jenkins, Mark A., Milne, Roger L., Moreno, Victor, Newcomb, Polly A., Nishihara, Reiko, Pai, Rish K., Sakoda, Lori C., Slattery, Martha L., Sun, Wei, Amitay, Efrat L., Alwers, Elizabeth, Thibodeau, Stephen N., Toland, Amanda E., van Guelpen, Bethany, Woods, Michael O., Zaidi, Syed H., Potter, John D., Giannakis, Marios, Song, Mingyang, Nowak, Jonathan A., Phipps, Amanda I., Peters, Ulrike, Ogino, Shuji, Ugai, Tomotaka, Haruki, Koichiro, Harrison, Tabitha A., Cao, Yin, Qu, Conghui, Chan, Andrew T., Campbell, Peter T., Akimoto, Naohiko, Berndt, Sonja, Brenner, Hermann, Buchanan, Daniel D., Chang-Claude, Jenny, Fujiyoshi, Kenji, Gallinger, Steven J., Gunter, Marc J., Hidaka, Akihisa, Hoffmeister, Michael, Hsu, Li, Jenkins, Mark A., Milne, Roger L., Moreno, Victor, Newcomb, Polly A., Nishihara, Reiko, Pai, Rish K., Sakoda, Lori C., Slattery, Martha L., Sun, Wei, Amitay, Efrat L., Alwers, Elizabeth, Thibodeau, Stephen N., Toland, Amanda E., van Guelpen, Bethany, Woods, Michael O., Zaidi, Syed H., Potter, John D., Giannakis, Marios, Song, Mingyang, Nowak, Jonathan A., Phipps, Amanda I., Peters, Ulrike, and Ogino, Shuji

Abstract

INTRODUCTION:Early-onset colorectal cancer diagnosed before the age of 50 years has been increasing. Likely reflecting the pathogenic role of the intestinal microbiome, which gradually changes across the entire colorectal length, the prevalence of certain tumor molecular characteristics gradually changes along colorectal subsites. Understanding how colorectal tumor molecular features differ by age and tumor location is important in personalized patient management. METHODS:Using 14,004 cases with colorectal cancer including 3,089 early-onset cases, we examined microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and KRAS and BRAF mutations in carcinomas of the cecum, ascending colon, transverse colon, descending colon, sigmoid colon, and rectum and compared early-onset cases with later-onset cases. RESULTS:The proportions of MSI-high, CIMP-high, and BRAF-mutated early-onset tumors were lowest in the rectum (8.8%, 3.4%, and 3.5%, respectively) and highest in the ascending colon (46% MSI-high; 15% CIMP-high) or transverse colon (8.6% BRAF-mutated) (all Ptrend<0.001 across the rectum to ascending colon). Compared with later-onset tumors, early-onset tumors showed a higher prevalence of MSI-high status and a lower prevalence of CIMP-high status and BRAF mutations in most subsites. KRAS mutation prevalence was higher in the cecum compared with that in the other subsites in both early-onset and later-onset tumors (P < 0.001). Notably, later-onset MSI-high tumors showed a continuous decrease in KRAS mutation prevalence from the rectum (36%) to ascending colon (9%; Ptrend<0.001), followed by an increase in the cecum (14%), while early-onset MSI-high cancers showed no such trend. DISCUSSION:Our findings support biogeographical and pathogenic heterogeneity of colorectal carcinomas in different colorectal subsites and age groups.

Published
2023
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13. Molecular Characteristics of Early-Onset Colorectal Cancer According to Detailed Anatomical Locations: Comparison With Later-Onset Cases

Author

Ugai, Tomotaka, primary, Haruki, Koichiro, additional, Harrison, Tabitha A., additional, Cao, Yin, additional, Qu, Conghui, additional, Chan, Andrew T., additional, Campbell, Peter T., additional, Akimoto, Naohiko, additional, Berndt, Sonja, additional, Brenner, Hermann, additional, Buchanan, Daniel D., additional, Chang-Claude, Jenny, additional, Fujiyoshi, Kenji, additional, Gallinger, Steven J., additional, Gunter, Marc J., additional, Hidaka, Akihisa, additional, Hoffmeister, Michael, additional, Hsu, Li, additional, Jenkins, Mark A., additional, Milne, Roger L., additional, Moreno, Victor, additional, Newcomb, Polly A., additional, Nishihara, Reiko, additional, Pai, Rish K., additional, Sakoda, Lori C., additional, Slattery, Martha L., additional, Sun, Wei, additional, Amitay, Efrat L., additional, Alwers, Elizabeth, additional, Thibodeau, Stephen N., additional, Toland, Amanda E., additional, Van Guelpen, Bethany, additional, Woods, Michael O., additional, Zaidi, Syed H., additional, Potter, John D., additional, Giannakis, Marios, additional, Song, Mingyang, additional, Nowak, Jonathan A., additional, Phipps, Amanda I., additional, Peters, Ulrike, additional, and Ogino, Shuji, additional

Published
2022
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14. Validation of the prognostic value of CD3 and CD8 cell densities analogous to the Immunoscore® by stage and location of colorectal cancer: an independent patient cohort study

Author

Alwers, Elizabeth, primary, Kather, Jakob N, additional, Kloor, Matthias, additional, Brobeil, Alexander, additional, Tagscherer, Katrin E, additional, Roth, Wilfried, additional, Echle, Amelie, additional, Amitay, Efrat L, additional, Chang‐Claude, Jenny, additional, Brenner, Hermann, additional, and Hoffmeister, Michael, additional

Published
2022
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17. Diabetes mellitus in relation to colorectal tumor molecular subtypes : a pooled analysis of more than 9000 cases

Author

Harlid, Sophia, van Guelpen, Bethany, Qu, Conghui, Gylling, Björn, 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, Harlid, Sophia, van Guelpen, Bethany, Qu, Conghui, Gylling, Björn, 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, and Peters, Ulrike

Abstract

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.

Published
2022
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18. Validation of the prognostic value of CD3 and CD8 cell densities analogous to the Immunoscore® by stage and location of colorectal cancer: an independent patient cohort study.

Author

Alwers, Elizabeth, Kather, Jakob N, Kloor, Matthias, Brobeil, Alexander, Tagscherer, Katrin E, Roth, Wilfried, Echle, Amelie, Amitay, Efrat L, Chang‐Claude, Jenny, Brenner, Hermann, and Hoffmeister, Michael

Subjects
PROPORTIONAL hazards models, PROGRESSION-free survival, COLORECTAL cancer, PROGNOSIS, TUMOR-infiltrating immune cells, CANCER patients, CD3 antigen
Abstract

In addition to the traditional staging system in colorectal cancer (CRC), the Immunoscore® has been proposed to characterize the level of immune infiltration in tumor tissue and as a potential prognostic marker. The aim of this study was to examine and validate associations of an immune cell score analogous to the Immunoscore® with established molecular tumor markers and with CRC patient survival in a routine setting. Patients from a population‐based cohort study with available CRC tumor tissue blocks were included in this analysis. CD3+ and CD8+ tumor infiltrating lymphocytes in the tumor center and invasive margin were determined in stained tumor tissue slides. Based on the T‐cell density in each region, an immune cell score closely analogous to the concept of the Immunoscore® was calculated and tumors categorized into IS‐low, IS‐intermediate, or IS‐high. Logistic regression models were used to assess associations between clinicopathological characteristics with the immune cell score, and Cox proportional hazards models to analyze associations with cancer‐specific, relapse‐free, and overall survival. From 1,535 patients with CRC, 411 (27%) had IS‐high tumors. Microsatellite instability (MSI‐high) was strongly associated with higher immune cell score levels (p < 0.001). Stage I–III patients with IS‐high had better CRC‐specific and relapse‐free survival compared to patients with IS‐low (hazard ratio [HR] = 0.42 [0.27–0.66] and HR = 0.45 [0.31–0.67], respectively). Patients with microsatellite stable (MSS) tumors and IS‐high had better survival (HRCSS = 0.60 [0.42–0.88]) compared to MSS/IS‐low patients. In this population‐based cohort of CRC patients, the immune cell score was significantly associated with better patient survival. It was a similarly strong prognostic marker in patients with MSI‐high tumors and in the larger group of patients with MSS tumors. Additionally, this study showed that it is possible to implement an analogous immune cell score approach and validate the Immunoscore® using open source software in an academic setting. Thus, the Immunoscore® could be useful to improve the traditional staging system in colon and rectal cancer used in clinical practice. [ABSTRACT FROM AUTHOR]

Published
2023
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19. Diabetes mellitus in relation to colorectal tumor molecular subtypes: A pooled analysis of more than 9000 cases

Author

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

Published
2022
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24. Intake of Dietary Fruit, Vegetables, and Fiber and Risk of Colorectal Cancer According to Molecular Subtypes : A Pooled Analysis of 9 Studies

Author

Hidaka, Akihisa, Harrison, Tabitha A., Cao, Yin, Sakoda, Lori C., Barfield, Richard, Giannakis, Marios, Song, Mingyang, Phipps, Amanda, I, Figueiredo, Jane C., Zaidi, Syed H., Toland, Amanda E., Amitay, Efrat L., Berndt, Sonja, I, Borozan, Ivan, Chan, Andrew T., Gallinger, Steven, Gunter, Marc J., Guinter, Mark A., Harlid, Sophia, Hampel, Heather, Jenkins, Mark A., Lin, Yi, Moreno, Victor, Newcomb, Polly A., Nishihara, Reiko, Ogino, Shuji, Obon-Santacana, Mireia, Parfrey, Patrick S., Potter, John D., Slattery, Martha L., Steinfelder, Robert S., Um, Caroline Y., Wang, Xiaoliang, Woods, Michael O., van Guelpen, Bethany, Thibodeau, Stephen N., Hoffmeister, Michael, Sun, Wei, Hsu, Li, Buchanan, Daniel D., Campbell, Peter T., Peters, Ulrike, Hidaka, Akihisa, Harrison, Tabitha A., Cao, Yin, Sakoda, Lori C., Barfield, Richard, Giannakis, Marios, Song, Mingyang, Phipps, Amanda, I, Figueiredo, Jane C., Zaidi, Syed H., Toland, Amanda E., Amitay, Efrat L., Berndt, Sonja, I, Borozan, Ivan, Chan, Andrew T., Gallinger, Steven, Gunter, Marc J., Guinter, Mark A., Harlid, Sophia, Hampel, Heather, Jenkins, Mark A., Lin, Yi, Moreno, Victor, Newcomb, Polly A., Nishihara, Reiko, Ogino, Shuji, Obon-Santacana, Mireia, Parfrey, Patrick S., Potter, John D., Slattery, Martha L., Steinfelder, Robert S., Um, Caroline Y., Wang, Xiaoliang, Woods, Michael O., van Guelpen, Bethany, Thibodeau, Stephen N., Hoffmeister, Michael, Sun, Wei, Hsu, Li, Buchanan, Daniel D., Campbell, Peter T., and Peters, Ulrike

Abstract

Protective associations of fruits, vegetables, and fiber intake with colorectal cancer risk have been shown in many, but not all epidemiologic studies. One possible reason for study heterogeneity is that dietary factors may have distinct effects by colorectal cancer molecular subtypes. Here, we investigate the association of fruit, vegetables, and fiber intake with four well-established colorectal cancer molecular subtypes separately and in combination. Nine observational studies including 9,592 cases with molecular subtypes for microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and somatic mutations in BRAF and KRAS genes, and 7,869 controls were analyzed. Both case-only logistic regression analyses and polytomous logistic regression analyses (with one control set and multiple case groups) were used. Higher fruit intake was associated with a trend toward decreased risk of BRAF-mutated tumors [OR 4th vs. 1st quartile = 0.82 (95% confidence interval, 0.65–1.04)] but not BRAF-wildtype tumors [1.09 (0.97–1.22); P difference as shown in case-only analysis = 0.02]. This difference was observed in case–control studies and not in cohort studies. Compared with controls, higher fiber intake showed negative association with colorectal cancer risk for cases with microsatellite stable/MSI-low, CIMP-negative, BRAF-wildtype, and KRAS-wildtype tumors (Ptrend range from 0.03 to 3.4e-03), which is consistent with the traditional adenoma-colorectal cancer pathway. These negative associations were stronger compared with MSI-high, CIMP-positive, BRAF-mutated, or KRAS-mutated tumors, but the differences were not statistically significant. These inverse associations for fruit and fiber intake may explain, in part, inconsistent findings between fruit or fiber intake and colorectal cancer risk that have previously been reported.

Published
2020
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25. Landscape of somatic single nucleotide variants and indels in colorectal cancer and impact on survival

Author

Zaidi, Syed H., Harrison, Tabitha A., Phipps, Amanda I., Steinfelder, Robert, Trinh, Quang M., Qu, Conghui, Banbury, Barbara L., Georgeson, Peter, Grasso, Catherine S., Giannakis, Marios, Adams, Jeremy B., Alwers, Elizabeth, Amitay, Efrat L., Barfield, Richard T., Berndt, Sonja, I, Borozan, Ivan, Brenner, Hermann, Brezina, Stefanie, Buchanan, Daniel D., Cao, Yin, Chan, Andrew T., Chang-Claude, Jenny, Connolly, Charles M., Drew, David A., Farris, Alton Brad, III, Figueiredo, Jane C., French, Amy J., Fuchs, Charles S., Garraway, Levi A., Gruber, Steve, Guinter, Mark A., Hamilton, Stanley R., Harlid, Sophia, Heisler, Lawrence E., Hidaka, Akihisa, Hopper, John L., Huang, Wen-Yi, Huyghe, Jeroen R., Jenkins, Mark A., Krzyzanowski, Paul M., Lemire, Mathieu, Lin, Yi, Luo, Xuemei, Mardis, Elaine R., McPherson, John D., Miller, Jessica K., Moreno, Victor, Mu, Xinmeng Jasmine, Nishihara, Reiko, Papadopoulos, Nickolas, Pasternack, Danielle, Quist, Michael J., Rafikova, Adilya, Reid, Emma E. G., Shinbrot, Eve, Shirts, Brian H., Stein, Lincoln D., Teney, Cherie D., Timms, Lee, Um, Caroline Y., van Guelpen, Bethany, Van Tassel, Megan, Wang, Xiaolong, Wheeler, David A., Yung, Christina K., Hsu, Li, Ogino, Shuji, Gsur, Andrea, Newcomb, Polly A., Gallinger, Steven, Hoffmeister, Michael, Campbell, Peter T., Thibodeau, Stephen N., Sun, Wei, Hudson, Thomas J., Peters, Ulrike, Zaidi, Syed H., Harrison, Tabitha A., Phipps, Amanda I., Steinfelder, Robert, Trinh, Quang M., Qu, Conghui, Banbury, Barbara L., Georgeson, Peter, Grasso, Catherine S., Giannakis, Marios, Adams, Jeremy B., Alwers, Elizabeth, Amitay, Efrat L., Barfield, Richard T., Berndt, Sonja, I, Borozan, Ivan, Brenner, Hermann, Brezina, Stefanie, Buchanan, Daniel D., Cao, Yin, Chan, Andrew T., Chang-Claude, Jenny, Connolly, Charles M., Drew, David A., Farris, Alton Brad, III, Figueiredo, Jane C., French, Amy J., Fuchs, Charles S., Garraway, Levi A., Gruber, Steve, Guinter, Mark A., Hamilton, Stanley R., Harlid, Sophia, Heisler, Lawrence E., Hidaka, Akihisa, Hopper, John L., Huang, Wen-Yi, Huyghe, Jeroen R., Jenkins, Mark A., Krzyzanowski, Paul M., Lemire, Mathieu, Lin, Yi, Luo, Xuemei, Mardis, Elaine R., McPherson, John D., Miller, Jessica K., Moreno, Victor, Mu, Xinmeng Jasmine, Nishihara, Reiko, Papadopoulos, Nickolas, Pasternack, Danielle, Quist, Michael J., Rafikova, Adilya, Reid, Emma E. G., Shinbrot, Eve, Shirts, Brian H., Stein, Lincoln D., Teney, Cherie D., Timms, Lee, Um, Caroline Y., van Guelpen, Bethany, Van Tassel, Megan, Wang, Xiaolong, Wheeler, David A., Yung, Christina K., Hsu, Li, Ogino, Shuji, Gsur, Andrea, Newcomb, Polly A., Gallinger, Steven, Hoffmeister, Michael, Campbell, Peter T., Thibodeau, Stephen N., Sun, Wei, Hudson, Thomas J., and Peters, Ulrike

Abstract

Colorectal cancer (CRC) is a biologically heterogeneous disease. To characterize its mutational profile, we conduct targeted sequencing of 205 genes for 2,105 CRC cases with survival data. Our data shows several findings in addition to enhancing the existing knowledge of CRC. We identify PRKCI, SPZ1, MUTYH, MAP2K4, FETUB, and TGFBR2 as additional genes significantly mutated in CRC. We find that among hypermutated tumors, an increased mutation burden is associated with improved CRC-specific survival (HR=0.42, 95% CI: 0.21-0.82). Mutations in TP53 are associated with poorer CRC-specific survival, which is most pronounced in cases carrying TP53 mutations with predicted 0% transcriptional activity (HR=1.53, 95% CI: 1.21-1.94). Furthermore, we observe differences in mutational frequency of several genes and pathways by tumor location, stage, and sex. Overall, this large study provides deep insights into somatic mutations in CRC, and their potential relationships with survival and tumor features. Large scale sequencing study is of paramount importance to unravel the heterogeneity of colorectal cancer. Here, the authors sequenced 205 cancer genes in more than 2000 tumours and identified additional mutated driver genes, determined that mutational burden and specific mutations in TP53 are associated with survival odds.

Published
2020
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27. Intake of Dietary Fruit, Vegetables, and Fiber and Risk of Colorectal Cancer According to Molecular Subtypes: A Pooled Analysis of 9 Studies

Author

Hidaka, Akihisa, primary, Harrison, Tabitha A., additional, Cao, Yin, additional, Sakoda, Lori C., additional, Barfield, Richard, additional, Giannakis, Marios, additional, Song, Mingyang, additional, Phipps, Amanda I., additional, Figueiredo, Jane C., additional, Zaidi, Syed H., additional, Toland, Amanda E., additional, Amitay, Efrat L., additional, Berndt, Sonja I., additional, Borozan, Ivan, additional, Chan, Andrew T., additional, Gallinger, Steven, additional, Gunter, Marc J., additional, Guinter, Mark A., additional, Harlid, Sophia, additional, Hampel, Heather, additional, Jenkins, Mark A., additional, Lin, Yi, additional, Moreno, Victor, additional, Newcomb, Polly A., additional, Nishihara, Reiko, additional, Ogino, Shuji, additional, Obón-Santacana, Mireia, additional, Parfrey, Patrick S., additional, Potter, John D., additional, Slattery, Martha L., additional, Steinfelder, Robert S., additional, Um, Caroline Y., additional, Wang, Xiaoliang, additional, Woods, Michael O., additional, Van Guelpen, Bethany, additional, Thibodeau, Stephen N., additional, Hoffmeister, Michael, additional, Sun, Wei, additional, Hsu, Li, additional, Buchanan, Daniel D., additional, Campbell, Peter T., additional, and Peters, Ulrike, additional

Published
2020
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28. Colonoscopy and Reduction of Colorectal Cancer Risk by Molecular Tumor Subtypes: A Population-Based Case-Control Study

Author

Hoffmeister, Michael, primary, Bläker, Hendrik, additional, Jansen, Lina, additional, Alwers, Elizabeth, additional, Amitay, Efrat L., additional, Carr, Prudence R., additional, Kloor, Matthias, additional, Herpel, Esther, additional, Roth, Wilfried, additional, Chang-Claude, Jenny, additional, and Brenner, Hermann, additional

Published
2020
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29. Association of BMI and major molecular pathological markers of colorectal cancer in men and women

Author

Carr, Prudence R, primary, Amitay, Efrat L, additional, Jansen, Lina, additional, Alwers, Elizabeth, additional, Roth, Wilfried, additional, Herpel, Esther, additional, Kloor, Matthias, additional, Schneider, Martin, additional, Bläker, Hendrik, additional, Chang-Claude, Jenny, additional, Brenner, Hermann, additional, and Hoffmeister, Michael, additional

Published
2020
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37. Association of Aspirin and Nonsteroidal Anti-Inflammatory Drugs With Colorectal Cancer Risk by Molecular Subtypes.

Author

Amitay, Efrat L, Carr, Prudence R, Jansen, Lina, Walter, Viola, Roth, Wilfried, Herpel, Esther, Kloor, Matthias, Bläker, Hendrik, Chang-Claude, Jenny, Brenner, Hermann, and Hoffmeister, Michael

Subjects
*GENETIC mutation, *ANTI-inflammatory agents, *COLORECTAL cancer, *ASPIRIN, *POPULATION-based case control, *HEREDITARY nonpolyposis colorectal cancer, *MOLECULAR association
Abstract

Background: Regular use of aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) for a longer period has been inversely associated with colorectal cancer (CRC) risk. However, CRC is a heterogenic disease, and little is known regarding the associations with molecular pathological subtypes.Methods: Analyses included 2444 cases with a first diagnosis of CRC and 3130 healthy controls from a German population-based case control study. Tumor tissue samples were analyzed for major molecular pathological features: microsatellite instability (MSI), CpG island methylator phenotype, B-Raf proto-oncogene serine/threonine kinase (BRAF) mutation, and Kirsten rat sarcoma viral oncogene homolog gene (KRAS) mutation. Information on past and current use of NSAIDs, including aspirin, was obtained by standardized interviews. Multinomial logistic regression models were used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). All statistical tests were two-sided.Results: Regular use of NSAIDs was associated with a reduced CRC risk if tumors were MSS (OR = 0.66, 95% CI = 0.57 to 0.77), BRAF wildtype (OR = 0.67, 95% CI = 0.58 to 0.78), or KRAS wildtype (OR = 0.68, 95% CI = 0.58 to 0.80). Regular NSAID use was less clearly and mostly not statistically significantly associated with CRC risk reduction for MSI-high, BRAF-mutated, or KRAS-mutated CRC. In more specific analyses on MSI-high CRC, regular use of NSAIDs was associated with much stronger risk reduction in the absence of BRAF or KRAS mutations (OR = 0.34, 95% CI = 0.18 to 0.65) but not with KRAS- or BRAF-mutated MSI-high CRC (Pheterogeneity < .001). Results for just aspirin use were similar.Conclusion: Our study suggests variation in risk reduction of CRC subtypes following regular use of NSAIDs and aspirin. Regular use of NSAIDs and aspirin may be more strongly associated with risk reduction of MSI-high CRC without KRAS or BRAF mutation. [ABSTRACT FROM AUTHOR]

Published
2019
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44. Molecular Characteristics of Early-Onset Colorectal Cancer According to Detailed Anatomical Locations: Comparison With Later-Onset Cases.

Author

Ugai T, Haruki K, Harrison TA, Cao Y, Qu C, Chan AT, Campbell PT, Akimoto N, Berndt S, Brenner H, Buchanan DD, Chang-Claude J, Fujiyoshi K, Gallinger SJ, Gunter MJ, Hidaka A, Hoffmeister M, Hsu L, Jenkins MA, Milne RL, Moreno V, Newcomb PA, Nishihara R, Pai RK, Sakoda LC, Slattery ML, Sun W, Amitay EL, Alwers E, Thibodeau SN, Toland AE, Van Guelpen B, Woods MO, Zaidi SH, Potter JD, Giannakis M, Song M, Nowak JA, Phipps AI, Peters U, and Ogino S

Subjects
Humans, Proto-Oncogene Proteins p21(ras) genetics, DNA Methylation, Mutation, Phenotype, CpG Islands, Microsatellite Instability, Proto-Oncogene Proteins B-raf genetics, Colorectal Neoplasms epidemiology, Colorectal Neoplasms genetics, Colorectal Neoplasms pathology
Abstract

Introduction: Early-onset colorectal cancer diagnosed before the age of 50 years has been increasing. Likely reflecting the pathogenic role of the intestinal microbiome, which gradually changes across the entire colorectal length, the prevalence of certain tumor molecular characteristics gradually changes along colorectal subsites. Understanding how colorectal tumor molecular features differ by age and tumor location is important in personalized patient management., Methods: Using 14,004 cases with colorectal cancer including 3,089 early-onset cases, we examined microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and KRAS and BRAF mutations in carcinomas of the cecum, ascending colon, transverse colon, descending colon, sigmoid colon, and rectum and compared early-onset cases with later-onset cases., Results: The proportions of MSI-high, CIMP-high, and BRAF -mutated early-onset tumors were lowest in the rectum (8.8%, 3.4%, and 3.5%, respectively) and highest in the ascending colon (46% MSI-high; 15% CIMP-high) or transverse colon (8.6% BRAF -mutated) (all Ptrend <0.001 across the rectum to ascending colon). Compared with later-onset tumors, early-onset tumors showed a higher prevalence of MSI-high status and a lower prevalence of CIMP-high status and BRAF mutations in most subsites. KRAS mutation prevalence was higher in the cecum compared with that in the other subsites in both early-onset and later-onset tumors ( P < 0.001). Notably, later-onset MSI-high tumors showed a continuous decrease in KRAS mutation prevalence from the rectum (36%) to ascending colon (9%; Ptrend <0.001), followed by an increase in the cecum (14%), while early-onset MSI-high cancers showed no such trend., Discussion: Our findings support biogeographical and pathogenic heterogeneity of colorectal carcinomas in different colorectal subsites and age groups., (Copyright © 2023 by The American College of Gastroenterology.)

Published
2023
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