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Grant Details

Grant Number: 5R21CA222940-02 Interpret this number
Primary Investigator: Wu, Kana
Organization: Harvard School Of Public Health
Project Title: Integrating Diet and Tissue Whole Exome Sequencing Data to Study Processed Meat and Colorectal Cancer
Fiscal Year: 2019


Abstract

Project Summary/Abstract Processed meat is an established risk factor for colorectal cancer (CRC), but underlying mechanisms are still unknown and intake in the US remains high. Further, the burden of cancer and other adverse health outcomes attributable to high processed meat intake has been estimated to contribute to over 644,000 deaths in 2013 worldwide. Hypothesized key mechanisms involve additives in processed meats such as nitrate or nitrite, precursors to carcinogenic N-nitroso compounds (NOCs), which are alkylating agents and can induce G > A transitions. Due to the lack of a long-term biomarker for NOC exposure, previous studies relating dietary intake of nitrate or NOCs to CRC have been inconsistent. Despite the dearth of scientific evidence directly linking N- nitroso compounds (NOC) per se to human cancers, processed meat items labeled “no nitrates/nitrites added” are increasingly being sold as a “healthy” alternative to traditional processed meats leading many consumers to believe that it is perfectly “safe” to consume “healthy” processed meat items. However, there is evidence from a limited number of studies that higher processed meat intake may be associated with CRC driver genes with higher frequency of G>A transitions, indicating a mechanistic link with NOCs. Recent advances in next generation high output sequencing have facilitated the assessment “mutational signatures” which are defined by the type of DNA damage resulting from certain DNA damaging agents, e.g., alkylating damage due to NOC exposure. We propose a very cost-effective study by using existing data from the Nurses' Health Study I (NHS) established in 1976 with 121,701 female nurses aged 30- 55 years at enrollment and the Health Professionals Follow-Up Study (HPFS) established in 1986 with 51,529 male health professionals aged 40-75 years. Self- administered questionnaires collected detailed data on lifestyle (updated every two years) and diet (updated every four years). Tumor tissues are also available in these cohorts. We will integrate repeated measures of diet and tumor tissue whole exome sequencing data (WES) to study underlying pathways. Aim 1a will assess whether cases with high processed meat intake have a higher frequency of G>A transitions in known and novel driver genes. Aim 1b will examine whether high processed meat consumers are more likely to exhibit a mutational signature indicative of alkylating DNA damage in their exome than those with low processed meat intake. Examining WES data in the context of our prospectively collected diet data provides an unprecedented opportunity to gain more insight into hypothesized or novel pathways and strengthen biologic plausibility. This knowledge is crucial to inform dietary guidelines for cancer prevention and guide food reformulation efforts. While avoiding processed meat is undoubtedly preferable, changing consumer choices is extremely time consuming. In the meantime, identifying interventions that can inhibit processed meat toxicity may be more effective to lessen the burden of cancers attributable to high processed meat consumption.



Publications

Gallstone Disease and Risk of Conventional Adenomas and Serrated Polyps: A Prospective Study.
Authors: Polychronidis G. , Wang K. , Lo C.H. , Wang L. , He M. , Knudsen M.D. , Wu K. , Joshi A.D. , Ogino S. , Giovannucci E.L. , et al. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2021-10-07; , .
EPub date: 2021-10-07.
PMID: 34620626
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Total Vitamin D Intake and Risks of Early-Onset Colorectal Cancer and Precursors.
Authors: Kim H. , Lipsyc-Sharf M. , Zong X. , Wang X. , Hur J. , Song M. , Wang M. , Smith-Warner S.A. , Fuchs C. , Ogino S. , et al. .
Source: Gastroenterology, 2021 Oct; 161(4), p. 1208-1217.e9.
EPub date: 2021-07-07.
PMID: 34245763
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Discovery and Features of an Alkylating Signature in Colorectal Cancer.
Authors: Gurjao C. , Zhong R. , Haruki K. , Li Y.Y. , Spurr L.F. , Lee-Six H. , Reardon B. , Ugai T. , Zhang X. , Cherniack A.D. , et al. .
Source: Cancer discovery, 2021 Oct; 11(10), p. 2446-2455.
EPub date: 2021-06-17.
PMID: 34140290
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Sugar-sweetened beverage, artificially sweetened beverage and sugar intake and colorectal cancer survival.
Authors: Zoltick E.S. , Smith-Warner S.A. , Yuan C. , Wang M. , Fuchs C.S. , Meyerhardt J.A. , Chan A.T. , Ng K. , Ogino S. , Stampfer M.J. , et al. .
Source: British journal of cancer, 2021 Sep; 125(7), p. 1016-1024.
EPub date: 2021-07-15.
PMID: 34267328
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The Sulfur Microbial Diet Is Associated With Increased Risk of Early-Onset Colorectal Cancer Precursors.
Authors: Nguyen L.H. , Cao Y. , Hur J. , Mehta R.S. , Sikavi D.R. , Wang Y. , Ma W. , Wu K. , Song M. , Giovannucci E.L. , et al. .
Source: Gastroenterology, 2021-07-14; , .
EPub date: 2021-07-14.
PMID: 34273347
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Changes in Lifestyle Factors After Endoscopic Screening: A Prospective Study in the United States.
Authors: Knudsen M.D. , Wang L. , Wang K. , Wu K. , Ogino S. , Chan A.T. , Giovannucci E. , Song M. .
Source: Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association, 2021-07-10; , .
EPub date: 2021-07-10.
PMID: 34256146
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Simple Sugar and Sugar-Sweetened Beverage Intake During Adolescence and Risk of Colorectal Cancer Precursors.
Authors: Joh H.K. , Lee D.H. , Hur J. , Nimptsch K. , Chang Y. , Joung H. , Zhang X. , Rezende L.F.M. , Lee J.E. , Ng K. , et al. .
Source: Gastroenterology, 2021 07; 161(1), p. 128-142.e20.
EPub date: 2021-03-19.
PMID: 33753105
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Sugar-sweetened beverage intake in adulthood and adolescence and risk of early-onset colorectal cancer among women.
Authors: Hur J. , Otegbeye E. , Joh H.K. , Nimptsch K. , Ng K. , Ogino S. , Meyerhardt J.A. , Chan A.T. , Willett W.C. , Wu K. , et al. .
Source: Gut, 2021-05-06; , .
EPub date: 2021-05-06.
PMID: 33958435
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Comprehensive Assessment of Diet Quality and Risk of Precursors of Early-Onset Colorectal Cancer.
Authors: Zheng X. , Hur J. , Nguyen L.H. , Liu J. , Song M. , Wu K. , Smith-Warner S.A. , Ogino S. , Willett W.C. , Chan A.T. , et al. .
Source: Journal of the National Cancer Institute, 2021-05-04; 113(5), p. 543-552.
PMID: 33136160
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Prognostic significance of myeloid immune cells and their spatial distribution in the colorectal cancer microenvironment.
Authors: Väyrynen J.P. , Haruki K. , Väyrynen S.A. , Lau M.C. , Dias Costa A. , Borowsky J. , Zhao M. , Ugai T. , Kishikawa J. , Akimoto N. , et al. .
Source: Journal for immunotherapy of cancer, 2021 04; 9(4), .
PMID: 33931472
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Alcohol intake in early adulthood and risk of colorectal cancer: three large prospective cohort studies of men and women in the United States.
Authors: Hur J. , Smith-Warner S.A. , Rimm E.B. , Willett W.C. , Wu K. , Cao Y. , Giovannucci E. .
Source: European journal of epidemiology, 2021 Mar; 36(3), p. 325-333.
EPub date: 2021-02-15.
PMID: 33586078
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Dairy intake during adolescence and risk of colorectal adenoma later in life.
Authors: Nimptsch K. , Lee D.H. , Zhang X. , Song M. , Farvid M.S. , Rezende L.F.M. , Cao Y. , Chan A.T. , Fuchs C. , Meyerhardt J. , et al. .
Source: British journal of cancer, 2021 03; 124(6), p. 1160-1168.
EPub date: 2021-01-04.
PMID: 33398066
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Periodontal disease, tooth loss, and risk of oesophageal and gastric adenocarcinoma: a prospective study.
Authors: Lo C.H. , Kwon S. , Wang L. , Polychronidis G. , Knudsen M.D. , Zhong R. , Cao Y. , Wu K. , Ogino S. , Giovannucci E.L. , et al. .
Source: Gut, 2021 03; 70(3), p. 620-621.
EPub date: 2020-07-20.
PMID: 32690603
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The Prognostic Role of Macrophage Polarization in the Colorectal Cancer Microenvironment.
Authors: Väyrynen J.P. , Haruki K. , Lau M.C. , Väyrynen S.A. , Zhong R. , Dias Costa A. , Borowsky J. , Zhao M. , Fujiyoshi K. , Arima K. , et al. .
Source: Cancer immunology research, 2021 01; 9(1), p. 8-19.
EPub date: 2020-10-06.
PMID: 33023967
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Glucosamine and Chondroitin Supplements and Risk of Colorectal Adenoma and Serrated Polyp.
Authors: Lee D.H. , Cao C. , Zong X. , Zhang X. , O'Connell K. , Song M. , Wu K. , Du M. , Cao Y. , Giovannucci E.L. , et al. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2020 12; 29(12), p. 2693-2701.
EPub date: 2020-10-14.
PMID: 33055203
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Body fatness over the life course and risk of serrated polyps and conventional adenomas.
Authors: Lo C.H. , He X. , Hang D. , Wu K. , Ogino S. , Chan A.T. , Giovannucci E.L. , Song M. .
Source: International journal of cancer, 2020-10-01; 147(7), p. 1831-1844.
EPub date: 2020-03-31.
PMID: 32150293
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Post-diagnosis dietary insulinemic potential and survival outcomes among colorectal cancer patients.
Authors: Tabung F.K. , Noonan A. , Lee D.H. , Song M. , Clinton S.K. , Spakowicz D. , Wu K. , Cheng E. , Meyerhardt J.A. , Fuchs C.S. , et al. .
Source: BMC cancer, 2020-08-27; 20(1), p. 817.
EPub date: 2020-08-27.
PMID: 32854644
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Prognostic Significance of Immune Cell Populations Identified by Machine Learning in Colorectal Cancer Using Routine Hematoxylin and Eosin-Stained Sections.
Authors: Väyrynen J.P. , Lau M.C. , Haruki K. , Väyrynen S.A. , Dias Costa A. , Borowsky J. , Zhao M. , Fujiyoshi K. , Arima K. , Twombly T.S. , et al. .
Source: Clinical cancer research : an official journal of the American Association for Cancer Research, 2020-08-15; 26(16), p. 4326-4338.
EPub date: 2020-05-21.
PMID: 32439699
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Periodontal Disease, Tooth Loss, and Risk of Serrated Polyps and Conventional Adenomas.
Authors: Lo C.H. , Nguyen L.H. , Wu K. , Ogino S. , Chan A.T. , Giovannucci E.L. , Song M. .
Source: Cancer prevention research (Philadelphia, Pa.), 2020 08; 13(8), p. 699-706.
PMID: 32727821
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Yogurt consumption and risk of conventional and serrated precursors of colorectal cancer.
Authors: Zheng X. , Wu K. , Song M. , Ogino S. , Fuchs C.S. , Chan A.T. , Giovannucci E.L. , Cao Y. , Zhang X. .
Source: Gut, 2020 05; 69(5), p. 970-972.
EPub date: 2019-06-17.
PMID: 31209182
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Dietary Intake of Branched-Chain Amino Acids and Risk of Colorectal Cancer.
Authors: Katagiri R. , Song M. , Zhang X. , Lee D.H. , Tabung F.K. , Fuchs C.S. , Meyerhardt J.A. , Nishihara R. , Chan A.T. , Joshi A.D. , et al. .
Source: Cancer prevention research (Philadelphia, Pa.), 2020 01; 13(1), p. 65-72.
EPub date: 2019-11-07.
PMID: 31699705
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Dietary intake of fiber, whole grains and risk of colorectal cancer: An updated analysis according to food sources, tumor location and molecular subtypes in two large US cohorts.
Authors: He X. , Wu K. , Zhang X. , Nishihara R. , Cao Y. , Fuchs C.S. , Giovannucci E.L. , Ogino S. , Chan A.T. , Song M. .
Source: International journal of cancer, 2019-12-01; 145(11), p. 3040-3051.
EPub date: 2019-05-21.
PMID: 31044426
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Physical activity during adolescence and risk of colorectal adenoma later in life: results from the Nurses' Health Study II.
Authors: Rezende L.F.M. , Lee D.H. , Keum N. , Nimptsch K. , Song M. , Lee I.M. , Eluf-Neto J. , Ogino S. , Fuchs C. , Meyerhardt J. , et al. .
Source: British journal of cancer, 2019 07; 121(1), p. 86-94.
EPub date: 2019-05-22.
PMID: 31114018
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