Proceedings of the second international molecular pathological epidemiology (MPE) meeting

Ogino, Shuji; Campbell, Peter T.; Nishihara, Reiko; Phipps, Amanda I.; Beck, Andrew H.; Sherman, Mark E.; Chan, Andrew T.; Troester, Melissa A.; Bass, Adam J.; Fitzgerald, Kathryn C.; Irizarry, Rafael A.; Kelsey, Karl T.; Nan, Hongmei; Peters, Ulrike; Poole, Elizabeth M.; Qian, Zhi Rong; Tamimi, Rulla M.; Tchetgen, Eric J. Tchetgen; Tworoger, Shelley S.; Zhang, Xuehong; Giovannucci, Edward; Brandt, Piet A. van den; Rosner, Bernard; Wang, Molin; Chatterjee, Nilanjan; Begg, Colin B.

doi:10.1007/s10552-015-0596-2

Cited by 42 publications

(28 citation statements)

References 145 publications

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“…The strengths of our study include the use of our molecular pathological epidemiology (50–52) database of rectal and colon carcinoma cases in the two U.S. nationwide, prospective cohort studies, which integrates clinicopathologic features, long-term survival data, and tumor molecular features including microRNA MIR21 expression in colorectal cancer tissue. This population-based colorectal cancer database enabled us to rigorously examine the interactive prognostic association of tumor MIR21 and PTGS2, controlling for potential confounders.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA MIR21 (miR-21) and PTGS2 Expression in Colorectal Cancer and Patient Survival

Mima

Nishihara

Yang

et al. 2016

Clinical Cancer Research

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Purpose Prostaglandin-endoperoxide synthase 2 (PTGS2, cyclooxygenase-2; a target of aspirin) produces inflammatory mediator prostaglandin E2 (PGE2), and contributes to colorectal neoplasia development. PTGS2-driven inflammatory responses can induce tumor expression of microRNA MIR21 (miR-21) that can increase local PGE2 level by downregulating PGE2-metabolizing enzymes. We hypothesized that the prognostic association of tumor MIR21 expression level in colorectal carcinoma might depend on inflammatory tumor microenvironment and be stronger in tumors expressing high-level PTGS2. Experimental Design Utilizing 765 rectal and colon cancer specimens in the Nurses’ Health Study and the Health Professionals Follow-up Study, we measured MIR21 expression by quantitative reverse-transcription PCR, and PTGS2 expression by immunohistochemistry. Cox proportional hazards regression model was used to assess statistical interaction between MIR21 and PTGS2 in colorectal cancer-specific survival analysis, controlling for potential confounders including microsatellite instability, CpG island methylator phenotype, LINE-1 methylation level, and KRAS, BRAF, and PIK3CA mutations. Results Tumor MIR21 expression level was associated with higher colorectal cancer-specific mortality (Ptrend = 0.029), and there was a statistically significant interaction between MIR21 and PTGS2 (Pinteraction = 0.0004). The association between MIR21 expression and colorectal cancer-specific mortality was statistically significant in PTGS2-high cancers (multivariable hazard ratio of the highest vs. lowest quartile of MIR21, 2.28; 95% confidence interval, 1.42 to 3.67; Ptrend = 0.0004) but not in PTGS2-absent/low cancers (Ptrend = 0.22). Conclusions MIR21 expression level in colorectal carcinoma is associated with worse clinical outcome, and this association is stronger in carcinomas expressing high-level PTGS2, suggesting complex roles of immunity and inflammation in tumor progression.

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Section: Discussionmentioning

confidence: 99%

MicroRNA MIR21 (miR-21) and PTGS2 Expression in Colorectal Cancer and Patient Survival

Mima

Nishihara

Yang

et al. 2016

Clinical Cancer Research

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“…This MPE approach can link exposures to specific molecular pathologic signatures, give clues to mechanisms, enhance causal inference, and identify potential biomarkers for clinical use. 70–75 Study participants were distributed throughout the U.S. and in general represent CRC cases in the U.S. population. Data on lifestyle and tumors were collected prospectively by investigators blinded to patient outcomes.…”

Section: Discussionmentioning

confidence: 99%

Survival Benefit of Exercise Differs by Tumor IRS1 Expression Status in Colorectal Cancer

et al. 2015

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Background High level physical activity is associated with lower colorectal cancer mortality, likely through insulin sensitization. IRS1 (insulin receptor substrate 1) is a mediator of insulin and insulin-like growth factor (IGF) signaling pathways, and its down-regulation is associated with insulin resistance. Therefore, we hypothesized that tumor IRS1 expression status might modify cellular sensitivity to insulin and IGF, and the prognostic association of physical activity. Methods We assessed IRS1 expression level in 371 stage I–III rectal and colon cancers in the Nurses’ Health Study and the Health Professionals Follow-up Study by immunohistochemistry. In survival analysis, Cox proportional hazards model was used to assess an interaction between post-diagnosis physical activity (ordinal scale of sex-specific quartiles Q1 to Q4) and IRS1 expression (ordinal scale of negative, low, and high), controlling for potential confounders including microsatellite instability, CpG island methylator phenotype, LINE-1 methylation level, and KRAS, BRAF and PIK3CA mutation status. Results There was a statistically significant interaction between post-diagnosis physical activity and tumor IRS1 expression in colorectal cancer-specific mortality analysis (Pinteraction=0.005). Multivariable hazard ratio (95% confidence interval) for higher post-diagnosis physical activity (Q3–Q4 vs. Q1–Q2) was 0.15 (0.02–1.38) in IRS1-negative group, 0.45 (0.19–1.03) in IRS1-low group, and 1.32 (0.50–3.53) in IRS1-high group. Conclusions The association of post-diagnosis physical activity with colorectal carcinoma patient survival may differ by tumor IRS1 expression level. If validated, tumor IRS1 expression status may serve as a predictive marker to identify subgroups of patients who might gain greater survival benefit from increased level of exercise.

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“…Similar to prediction of breast cancer recurrence risk, prediction of primary breast cancer risk needs to consider the heterogeneity of breast cancer; however, these efforts are hindered by the paucity of risk factors identified for more aggressive breast cancer (23,24). Consequently, there is a need to combine achievements gained in both basic science and epidemiology into trans-disciplinary approaches as discussed by Colditz and colleagues (25), and exemplified by a recent meeting in molecular pathologic epidemiology (26).…”

Section: Breast Cancer Risk Prediction Modelsmentioning

confidence: 99%

Towards Prevention of Breast Cancer: What Are the Clinical Challenges?

Borgquist

Hall

Lipkus

et al. 2018

Cancer Prevention Research

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The dramatic increase in breast cancer incidence compels a paradigm shift in our preventive efforts. There are several barriers to overcome before prevention becomes an established part of breast cancer management. The objective of this review is to identify the clinical challenges for improved breast cancer prevention and discuss current knowledge on breast cancer risk assessment methods, risk communication, ethics, and interventional efforts with the aim of covering the aspects relevant for a breast cancer prevention trial. Herein, the following five areas are discussed: (i) Adequate tools for identification of women at high risk of breast cancer suggestively entitled Prevent! Breast cancer is the most common cancer in women worldwide with a steady increase in incidence, particularly in the developing world (1-3). An expanding middle class and a more westernized lifestyle contribute to increasing breast cancer rates in less developed countries as well (4-7), while limited health care resources and insufficient infrastructure challenge the management of the rising number of breast cancer patients (8). The dramatic increase in breast cancer incidence compels a paradigm shift in our preventive efforts. Despite the increasing incidence, few preventive measures have been implemented apart from identification and surveillance of genetically identified high-risk women with BRCA1 and BRCA2 mutations (9). Early detection through mammography screening and treatment of newly diagnosed cancers represent current clinical standards. There are several barriers to overcome before prevention becomes an established part of breast cancer management (Table 1). Consequently, the success of prevention efforts relies strongly on an ambitious interdisciplinary approach dedicated to the potential high-yield gain of intercepting breast cancer development (10).The initiative to this review originated while preparing a breast cancer prevention trial and identifying the gap of comprehensively bridging, not only risk assessment and intervention, but also communication of risk. Thus, the objective of this review is to identify the clinical challenges for improved breast cancer prevention and discuss current knowledge on breast cancer risk assessment methods, risk communication, ethics, and interventional efforts with the aim of covering aspects relevant for a prevention trial. Future comprehensive risk prediction models and effective communication hereof hopefully will allow for state-ofthe-art identification of high-risk women among whom individualized surveillance and prevention through adequate intervention can reduce breast cancer incidence. Breast Cancer Risk Prediction ModelsCurrent breast cancer risk assessment tools and prediction modelsThe identification of women at increased risk for developing breast cancer improves the likelihood these women will benefit from intensified surveillance and/or preventive intervention. Risk assessment systems have been developed successfully for women with a strong family history of breast c...

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Proceedings of the second international molecular pathological epidemiology (MPE) meeting

Cited by 42 publications

References 145 publications

MicroRNA MIR21 (miR-21) and PTGS2 Expression in Colorectal Cancer and Patient Survival

MicroRNA MIR21 (miR-21) and PTGS2 Expression in Colorectal Cancer and Patient Survival

Survival Benefit of Exercise Differs by Tumor IRS1 Expression Status in Colorectal Cancer

Towards Prevention of Breast Cancer: What Are the Clinical Challenges?

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