Inflammation and Colorectal Neoplasia

Summary

Principal Investigator: Andrew T Chan
Abstract: DESCRIPTION (provided by applicant): As the first independent application led by an NCI K career development award recipient, this proposal will address central hypotheses in inflammation, a NIH Major Roadmap Initiative for 2008. Considerable experimental, epidemiological, and clinical data strongly support a causative link between inflammation and colorectal cancer (CRC). A compelling proof of this principle is six randomized trials that demonstrate that anti- inflammatory drugs such as aspirin and cyclooxygenase-2 (COX-2) selective inhibitors reduce the risk of colorectal adenoma among patients with a prior history of colorectal neoplasia. The pro-inflammatory COX-2 enzyme appears to be a central mediator of this relationship. Recently, in two large prospective cohorts, the Nurses'Health Study (NHS) and the Health Professionals Follow-up Study (HPFS), we observed that aspirin reduces risk of COX-2 positive CRC but not risk of COX-2 negative CRC. This work has raised "...important questions about the biological basis and clinical implications of discovering differences between colon cancers that express high or low levels of COX-2." This statement, especially considered within the context of uncertainty regarding the optimal use of aspirin and non-steroidal anti-inflammatory drugs in light of their associated toxicities, highlights the critical need to further elucidate 1) lifestyle, dietary, and biochemical markers of susceptibility to COX-2 positive CRCs;2) underlying inflammatory and related prostaglandin pathways in aspirin-mediated inhibition of colorectal carcinogenesis. We will address these aims through studies which utilize the extensive questionnaire data, archived plasma and urine specimens, and tumor blocks already established for the NHS and HPFS cohorts and where needed, expand and collect more data to support our aims. Beyond our specific hypotheses, the resources generated in this proposal will allow for the rapid examination of future hypotheses as they emerge. As such, this application is a cost-efficient investment in improving our understanding of the key role of inflammation in colorectal neoplasia. Ultimately, the findings of this proposal may lead to improved risk stratification for tailoring preventative strategies utilizing lifestyle modification or chemopreventative agents that maximize efficacy but minimize toxicity. PUBLIC HEALTH RELEVANCE: Although aspirin can prevent colorectal cancer, a leading cause of death in the U.S., its optimal use in light of its toxicities remains uncertain. We will investigate the role of inflammation in colorectal carcinogenesis to define predictors of susceptibility for tailored preventative strategies.
Funding Period: 2009-09-29 - 2014-07-31
more information: NIH RePORT

Top Publications

  1. pmc Hormone therapy increases risk of ulcerative colitis but not Crohn's disease
    Hamed Khalili
    Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA
    Gastroenterology 143:1199-206. 2012
  2. pmc Psoriasis, psoriatic arthritis and increased risk of incident Crohn's disease in US women
    Wen Qing Li
    Department of Dermatology, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    Ann Rheum Dis 72:1200-5. 2013
  3. pmc Association between depressive symptoms and incidence of Crohn's disease and ulcerative colitis: results from the Nurses' Health Study
    Ashwin N Ananthakrishnan
    Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
    Clin Gastroenterol Hepatol 11:57-62. 2013
  4. pmc Statins and colorectal cancer
    Paul Lochhead
    Gastrointestinal Research Group, Division of Applied Medicine, Institute of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom
    Clin Gastroenterol Hepatol 11:109-18; quiz e13-4. 2013
  5. pmc A pooled analysis of smoking and colorectal cancer: timing of exposure and interactions with environmental factors
    Jian Gong
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA 98109, USA
    Cancer Epidemiol Biomarkers Prev 21:1974-85. 2012
  6. pmc Aspirin use, tumor PIK3CA mutation, and colorectal-cancer survival
    Xiaoyun Liao
    Department of Medical Oncology, Dana Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA
    N Engl J Med 367:1596-606. 2012
  7. pmc Phenotypic and tumor molecular characterization of colorectal cancer in relation to a susceptibility SMAD7 variant associated with survival
    Xabier Garcia-Albeniz
    Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA
    Carcinogenesis 34:292-8. 2013
  8. pmc Common single-nucleotide polymorphisms in the estrogen receptor β promoter are associated with colorectal cancer survival in postmenopausal women
    Michael N Passarelli
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
    Cancer Res 73:767-75. 2013
  9. pmc A prospective study of bisphosphonate use and risk of colorectal cancer
    Hamed Khalili
    Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
    J Clin Oncol 30:3229-33. 2012
  10. pmc Oral contraceptives, reproductive factors and risk of inflammatory bowel disease
    Hamed Khalili
    Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA
    Gut 62:1153-9. 2013

Research Grants

Detail Information

Publications80

  1. pmc Hormone therapy increases risk of ulcerative colitis but not Crohn's disease
    Hamed Khalili
    Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA
    Gastroenterology 143:1199-206. 2012
    ..The role of postmenopausal hormone therapy on risk of Crohn's disease (CD) and ulcerative colitis (UC) is unclear...
  2. pmc Psoriasis, psoriatic arthritis and increased risk of incident Crohn's disease in US women
    Wen Qing Li
    Department of Dermatology, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    Ann Rheum Dis 72:1200-5. 2013
    ..We aimed to evaluate the association between psoriasis, psoriatic arthritis and incident CD and UC among women in the USA...
  3. pmc Association between depressive symptoms and incidence of Crohn's disease and ulcerative colitis: results from the Nurses' Health Study
    Ashwin N Ananthakrishnan
    Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
    Clin Gastroenterol Hepatol 11:57-62. 2013
    ..Although many mechanisms have been proposed to link these disorders, few prospective studies have examined the relationship between depressed mood and incidence of CD or UC...
  4. pmc Statins and colorectal cancer
    Paul Lochhead
    Gastrointestinal Research Group, Division of Applied Medicine, Institute of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom
    Clin Gastroenterol Hepatol 11:109-18; quiz e13-4. 2013
    ..Herein, we review the epidemiologic, clinical, and preclinical data relevant to statins and colorectal neoplasia, and discuss the current status and future potential of statins as chemopreventive agents...
  5. pmc A pooled analysis of smoking and colorectal cancer: timing of exposure and interactions with environmental factors
    Jian Gong
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA 98109, USA
    Cancer Epidemiol Biomarkers Prev 21:1974-85. 2012
    ..What is unclear, however, is the impact of quitting smoking on risk attenuation and whether other risk factors for CRC modify this association...
  6. pmc Aspirin use, tumor PIK3CA mutation, and colorectal-cancer survival
    Xiaoyun Liao
    Department of Medical Oncology, Dana Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA
    N Engl J Med 367:1596-606. 2012
    ....
  7. pmc Phenotypic and tumor molecular characterization of colorectal cancer in relation to a susceptibility SMAD7 variant associated with survival
    Xabier Garcia-Albeniz
    Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA
    Carcinogenesis 34:292-8. 2013
    ..These findings suggest that individuals with this SMAD7 variant that develop CRC are more probably to have tumors with greater invasiveness and methylation of RUNX3, which potentially contributes to their poorer observed survival...
  8. pmc Common single-nucleotide polymorphisms in the estrogen receptor β promoter are associated with colorectal cancer survival in postmenopausal women
    Michael N Passarelli
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
    Cancer Res 73:767-75. 2013
    ..79; CI, 0.64-0.98 in replication]. No associations were noted for SNPs of AR, ESR1, or PGR. SNPs in the promoter of ESR2 may be important to pathways related to the association between ERβ and tumor progression and metastasis...
  9. pmc A prospective study of bisphosphonate use and risk of colorectal cancer
    Hamed Khalili
    Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
    J Clin Oncol 30:3229-33. 2012
    ..A recent case-control study showed an inverse association between bisphosphonate use and colorectal cancer. Data from prospective cohorts are lacking...
  10. pmc Oral contraceptives, reproductive factors and risk of inflammatory bowel disease
    Hamed Khalili
    Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA
    Gut 62:1153-9. 2013
    ..Oral contraceptive use has been associated with risk of Crohn's disease (CD) and ulcerative colitis (UC)...
  11. pmc Aspirin, nonsteroidal anti-inflammatory drug use, and risk for Crohn disease and ulcerative colitis: a cohort study
    Ashwin N Ananthakrishnan
    Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
    Ann Intern Med 156:350-9. 2012
    ..Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) are anti-inflammatory but have been linked in some studies to Crohn disease (CD) and ulcerative colitis (UC)...
  12. pmc Assessment of colorectal cancer molecular features along bowel subsites challenges the conception of distinct dichotomy of proximal versus distal colorectum
    Mai Yamauchi
    Department of Medical Oncology, Dana Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA
    Gut 61:847-54. 2012
    ..Considering a possible role of bowel contents (including microbiome) in carcinogenesis, this study hypothesised that tumour molecular features might gradually change along bowel subsites, rather than change abruptly at splenic flexure...
  13. pmc Predictors of lymph node count in colorectal cancer resections: data from US nationwide prospective cohort studies
    Teppei Morikawa
    Department of Medical Oncology, Dana Farber Cancer Institute and Havard Medical School, Boston, MA 02215, USA
    Arch Surg 147:715-23. 2012
    ..To identify factors that influence the total and negative lymph node counts in colorectal cancer resection specimens independent of pathologists and surgeons...
  14. pmc Postmenopausal hormone therapy is associated with a reduced risk of colorectal cancer lacking CDKN1A expression
    Jennifer H Lin
    Division of Preventive Medicine, Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02215, USA
    Cancer Res 72:3020-8. 2012
    ..Together, our molecular pathological epidemiology findings suggest a preventive effect of hormone therapy against colorectal carcinogenesis that depends, in part, on loss of cyclin-dependent kinase inhibitor CDKN1A...
  15. pmc Association between colorectal cancer susceptibility loci and survival time after diagnosis with colorectal cancer
    Amanda I Phipps
    Cancer Prevention Program, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA
    Gastroenterology 143:51-4.e4. 2012
    ..05-1.30; P = .005). Other SNPs were not associated significantly with survival. Common germline variations might be prognostic factors for patients with CRC. A variant in SMAD7 could affect progression of CRC...
  16. pmc Prospective study of family history and colorectal cancer risk by tumor LINE-1 methylation level
    Shuji Ogino
    Center for Molecular Oncologic Pathology, Dana Farber Cancer Institute, Brigham and Women s Hospital, Harvard Medical School, 450 Brookline Ave, Rm JF 215C, Boston, MA 02215, USA
    J Natl Cancer Inst 105:130-40. 2013
    ..We tested the hypothesis that CRC family history might confer a higher risk of LINE-1 methylation-low CRC...
  17. pmc Association between sex hormones and colorectal cancer risk in men and women
    Jennifer H Lin
    Division of Preventive Medicine, Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02215, USA
    Clin Gastroenterol Hepatol 11:419-424.e1. 2013
    ..There is observational and clinical evidence that indicates that sex hormones affect development of colorectal cancer in men and women. However, the relationship between endogenous sex hormone levels and colorectal cancer is unclear...
  18. pmc No association between germline variation in catechol-O-methyltransferase and colorectal cancer survival in postmenopausal women
    Michael N Passarelli
    From the 1Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 2Department of Epidemiology, University of Washington School of Public Health, Seattle, WA 3Division of General Medical Disciplines, Stanford University School of Medicine, Stanford, CA 4SRI International, Menlo Park, CA 5Department of Biostatistics, University of Washington School of Public Health, Seattle, WA 6Integrated Cancer Genomics Division, Translational Genomics Research Institute, Phoenix, AZ 7Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA and 8Channing Division of Network Medicine, Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, MA
    Menopause 21:415-20. 2014
    ..Because catechol-O-methyltransferase (COMT; 22q11.21) activity is an important component of estrogen-mediated carcinogenesis, we hypothesized that germline variation in COMT may be associated with CRC survival...
  19. pmc Genetic predictors of circulating 25-hydroxyvitamin d and risk of colorectal cancer
    Linda T Hiraki
    Authors Affiliations Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Departments of Nutrition, and Biostatistics, Harvard School of Public Health Department of Medicine, and Channing Division of Network Medicine, Brigham and Women s Hospital Division of Gastroenterology, Massachusetts General Hospital Department of Medicine, Harvard Medical School Gastrointestinal Malignancy Program, and Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts Public Health Sciences Division, Fred Hutchinson Cancer Research Center Department of Epidemiology, University of Washington School of Public Health, Seattle, Washington Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, North Carolina Divisions of Cancer Epidemiology and Genetics, and Cancer Control and Population Sciences, National Cancer Institute, NIH, Bethesda University of Maryland, School of Medicine, Baltimore, Maryland Service de Génétique Médicale, CHU Nantes, Nantes, France Divisions of Clinical Epidemiology and Aging Research and Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany Division of Research, Kaiser Permanente Medical Care Program, Oakland Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California Translational Genomics Research Institute, Phoenix, Arizona Department of Surgery, Turkey
    Cancer Epidemiol Biomarkers Prev 22:2037-46. 2013
    ..The identified single-nucleotide polymorphisms (SNPs) from four gene regions collectively explain approximately 5% of the variance in circulating 25(OH)D...
  20. pmc Long-term colorectal-cancer incidence and mortality after lower endoscopy
    Reiko Nishihara
    Department of Medical Oncology, Dana Farber Cancer Institute and Harvard Medical School, Boston, MA, USA
    N Engl J Med 369:1095-105. 2013
    ..Colonoscopy and sigmoidoscopy provide protection against colorectal cancer, but the magnitude and duration of protection, particularly against cancer of the proximal colon, remain uncertain...
  21. pmc Physical activity and risk of inflammatory bowel disease: prospective study from the Nurses' Health Study cohorts
    Hamed Khalili
    Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston MA 02114, USA
    BMJ 347:f6633. 2013
    ..To examine the association between physical activity and risk of ulcerative colitis and Crohn's disease...
  22. pmc Aspirin use, 8q24 single nucleotide polymorphism rs6983267, and colorectal cancer according to CTNNB1 alterations
    Hongmei Nan
    Affiliations of authors Division of Cancer Epidemiology, Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD HN Channing Division of Network Medicine, Department of Medicine HN, DJH, ELG, CSF, ATC and Department of Epidemiology DJH, PK, ELG, SO, Brigham and Women s Hospital and Harvard Medical School, Boston, MA Center for Molecular Oncologic Pathology TM, YI, AK, MY, SO, Department of Medical Oncology TM, MS, YI, AK, MY, CSF, SO, MLF, and Department of Biostatistics and Computational Biology LW, Dana Farber Cancer Institute, Boston, MA Department of Epidemiology DJH, ELG, SO and Department of Nutrition, Harvard School of Public Health, Boston, Simancas 47130
    J Natl Cancer Inst 105:1852-61. 2013
    ....
  23. pmc A prospective study of macrophage inhibitory cytokine-1 (MIC-1/GDF15) and risk of colorectal cancer
    Raaj S Mehta
    Affiliations of authors Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA RSM, ATC Gastrointestinal Research Group, Institute of Medical Sciences, Aberdeen University, Aberdeen, United Kingdom NB Department of Epidemiology XG, SO, ELG and Department of Nutrition MS, KW, XG, ELG, Harvard School of Public Health, Boston, MA Department of Pathology, University of Tokyo, Tokyo, Japan TM Channing Division of Network Medicine, Department of Medicine CSF, ELG, ATC and Department of Pathology SO, Brigham and Women s Hospital and Harvard Medical School, Boston, MA Department of Medical Oncology, Dana Farber Cancer Institute and Harvard Medical School, Boston, MA CSF, SO
    J Natl Cancer Inst 106:dju016. 2014
    ..Chronic inflammation plays a role in the development of colorectal cancer (CRC). The novel plasma inflammatory biomarker macrophage inhibitory cytokine-1 (MIC-1, GDF15) may have a direct mechanistic role in colorectal carcinogenesis...
  24. pmc Aspirin and the risk of colorectal cancer in relation to the expression of 15-hydroxyprostaglandin dehydrogenase (HPGD)
    Stephen P Fink
    Department of Medicine and Case Comprehensive Cancer Center, Case Western Reserve University and University Hospitals Case Medical Center, 10900 Euclid Avenue, Cleveland, OH 44106, USA
    Sci Transl Med 6:233re2. 2014
    ..This suggests that 15-PGDH expression level in normal colon mucosa may serve as a biomarker that may predict stronger benefit from aspirin chemoprevention. ..
  25. pmc Urinary PGE-M levels are associated with risk of colorectal adenomas and chemopreventive response to anti-inflammatory drugs
    Navya Bezawada
    Authors Affiliations University of Aberdeen, Aberdeen, United Kingdom Departments of
    Cancer Prev Res (Phila) 7:758-65. 2014
    ..Urinary PGE-M may serve as a biomarker to define subsets of the population who may obtain differential chemopreventive benefit from anti-inflammatory drugs...
  26. pmc Plasma adiponectin and soluble leptin receptor and risk of colorectal cancer: a prospective study
    Mingyang Song
    Division of Nutrition, Harvard Medical School, Boston, MA 02114, USA
    Cancer Prev Res (Phila) 6:875-85. 2013
    ..These findings support a role for adiponectin in colorectal carcinogenesis in men. Further studies are warranted to confirm these associations and elucidate potential underlying mechanisms...
  27. pmc Aspirin use and risk of colorectal cancer according to BRAF mutation status
    Reiko Nishihara
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02215, USA
    JAMA 309:2563-71. 2013
    ....
  28. pmc Molecular pathological epidemiology of epigenetics: emerging integrative science to analyze environment, host, and disease
    Shuji Ogino
    Department of Pathology, Brigham and Women s Hospital, and Harvard Medical School, Boston, MA 02215, USA
    Mod Pathol 26:465-84. 2013
    ....
  29. pmc Early life factors and risk of inflammatory bowel disease in adulthood
    Hamed Khalili
    Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA
    Inflamm Bowel Dis 19:542-7. 2013
    ..Early life factors have been postulated to play a role in development of immune tolerance and intestinal microbiome, which in turn may influence the risk of inflammatory bowel disease...
  30. pmc Prospective analysis of body mass index, physical activity, and colorectal cancer risk associated with β-catenin (CTNNB1) status
    Teppei Morikawa
    Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, 450 Brookline Ave, Boston, MA 02215, USA
    Cancer Res 73:1600-10. 2013
    ..Furthermore, they suggest that energy balance and metabolism status exerts its effect in a specific carcinogenesis pathway that is less likely dependent on WNT/CTNNB1 activation. Cancer Res; 73(5); 1600-10. ©2012 AACR...
  31. pmc Prospective cohort studies of bowel movement frequency and laxative use and colorectal cancer incidence in US women and men
    Xuehong Zhang
    Channing Division of Network Medicine, Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    Cancer Causes Control 24:1015-24. 2013
    ..The associations between bowel movement frequency, laxative use, and colorectal cancer incidence remain uncertain. No published studies have accounted for potential latency between these factors and colorectal cancer onset...
  32. pmc A prospective study of plasma inflammatory markers and risk of colorectal cancer in men
    M Song
    Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA
    Br J Cancer 108:1891-8. 2013
    ..Chronic inflammation may mediate risk of colorectal cancer (CRC); however, the association between circulating inflammatory markers and risk of CRC has been inconsistent...
  33. pmc Physical activity, tumor PTGS2 expression, and survival in patients with colorectal cancer
    Mai Yamauchi
    Department of Medical Oncology, Dana Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA
    Cancer Epidemiol Biomarkers Prev 22:1142-52. 2013
    ....
  34. pmc A prospective study of duration of smoking cessation and colorectal cancer risk by epigenetics-related tumor classification
    Reiko Nishihara
    Department of Medical Oncology, Dana Farber Cancer Institute, Department of Epidemiology, Harvard School of Public Health, 450 Brookline Avenue, Room JF 215C, Boston, MA 02215, USA
    Am J Epidemiol 178:84-100. 2013
    ..These molecular pathological epidemiology data suggest a protective effect of smoking cessation on a DNA methylation-related carcinogenesis pathway leading to CIMP-high colorectal cancer. ..
  35. pmc Discovery of colorectal cancer PIK3CA mutation as potential predictive biomarker: power and promise of molecular pathological epidemiology
    S Ogino
    1 Department of Pathology, Brigham and Women s Hospital, Harvard Medical School, Boston, MA, USA 2 Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA, USA 3 Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA
    Oncogene 33:2949-55. 2014
    ..As consequences, next-generation hybrid molecular biological and population scientists can advance science, moving closer to personalized precision medicine and health care...
  36. pmc Characterization of gene-environment interactions for colorectal cancer susceptibility loci
    Carolyn M Hutter
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
    Cancer Res 72:2036-44. 2012
    ....
  37. pmc Body mass index and risk of colorectal cancer according to fatty acid synthase expression in the nurses' health study
    Aya Kuchiba
    Department of Medical Oncology, Dana Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA
    J Natl Cancer Inst 104:415-20. 2012
    ..9 and 7.1, respectively, per 100,000 person-years. This molecular pathological epidemiology study supports a role of energy metabolism in colorectal cancer pathogenesis...
  38. pmc Role of vitamin and mineral supplementation and aspirin use in cancer survivors
    Edward Giovannucci
    ScD, Department of Nutrition, Harvard School of Public Health, 665 Huntington Ave, Boston, MA 02115, USA
    J Clin Oncol 28:4081-5. 2010
    ..The potential beneficial or adverse effects of dietary supplements and aspirin in survivors of cancer warrant further study...
  39. pmc Prognostic significance of AMP-activated protein kinase expression and modifying effect of MAPK3/1 in colorectal cancer
    Y Baba
    Department of Medical Oncology, Dana Farber Cancer Institute and Harvard Medical School, 44 Binney Street, Room JF 215C, Boston, MA 02115, USA
    Br J Cancer 103:1025-33. 2010
    ..AMP-activated protein kinase activation is cytotoxic to cancer cells, supporting AMPK as a tumour suppressor and a potential therapeutic target. However, no study has examined its prognostic role in colorectal cancers...
  40. pmc Cathepsin B expression and survival in colon cancer: implications for molecular detection of neoplasia
    Andrew T Chan
    Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
    Cancer Epidemiol Biomarkers Prev 19:2777-85. 2010
    ..Proteases play a critical role in tumorigenesis and are upregulated in colorectal cancer and neoplastic polyps. In animal models, cathepsin B (CTSB)-activatable imaging agents show high enzyme activity within intestinal tumors...
  41. pmc Dietary insulin load, dietary insulin index, and colorectal cancer
    Ying Bao
    Channing Laboratory, Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115, USA
    Cancer Epidemiol Biomarkers Prev 19:3020-6. 2010
    ..On the basis of a novel insulin index for individual foods, we estimated insulin demand for overall diets and assessed its association with colorectal cancer in the Nurses' Health Study and Health Professionals Follow-up Study...
  42. pmc Molecular pathological epidemiology of colorectal neoplasia: an emerging transdisciplinary and interdisciplinary field
    Shuji Ogino
    Department of Pathology, Brigham and Women s Hospital, Harvard Medical School, Boston, MA, USA
    Gut 60:397-411. 2011
    ..In this review, we overview this relatively new field of research and discuss measures to overcome challenges and move this field forward...
  43. pmc Inflammatory markers are associated with risk of colorectal cancer and chemopreventive response to anti-inflammatory drugs
    Andrew T Chan
    Gastrointestinal Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA
    Gastroenterology 140:799-808, quiz e11. 2011
    ..We investigated whether plasma inflammatory markers were associated with risk of CRC and if use of anti-inflammatory drugs was differentially associated with risk of CRC according to levels of inflammatory markers...
  44. pmc ABO blood group and risk of colorectal cancer
    Hamed Khalili
    Division of Gastroenterology, Massachusetts General Hospital, Boston, MA 02114, USA
    Cancer Epidemiol Biomarkers Prev 20:1017-20. 2011
    ..Recent studies have shown an association between non-O blood group and risk of pancreatic cancer. It is unclear whether this association is observed with other gastrointestinal malignancies, including colorectal cancers...
  45. pmc Phosphorylated AKT expression is associated with PIK3CA mutation, low stage, and favorable outcome in 717 colorectal cancers
    Yoshifumi Baba
    Department of Medical Oncology, Dana Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA
    Cancer 117:1399-408. 2011
    ..The PI3K/AKT pathway was commonly activated in human cancers and was recognized as a potential target for anticancer therapy. Nonetheless, clinical, molecular, or prognostic features of AKT-activated colon cancer remained uncertain...
  46. pmc Primary prevention of colorectal cancer
    Andrew T Chan
    Gastrointestinal Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
    Gastroenterology 138:2029-2043.e10. 2010
    ..Taken together, modifications in diet and lifestyle should substantially reduce the risk of colorectal cancer and could complement screening in reducing colorectal cancer incidence...
  47. pmc PIK3CA mutation is associated with poor prognosis among patients with curatively resected colon cancer
    Shuji Ogino
    Department of Medical Oncology, Dana Farber Cancer Institute, Brigham and Women s Hospital, Harvard Medical School, 44 Binney St, Room JF 215C, Boston, MA 02115 USA
    J Clin Oncol 27:1477-84. 2009
    ..PIK3CA mutation and subsequent activation of the AKT pathway play an important role in colorectal carcinogenesis. However, little is known about the prognostic role of PIK3CA mutation in colon cancer...
  48. pmc A cohort study of STMN1 expression in colorectal cancer: body mass index and prognosis
    Shuji Ogino
    Department of Medical Oncology, Center for Molecular Oncologic Pathology, Dana Farber Cancer Institute, Brigham and Women s Hospital and Harvard Medical School, 44 Binney St, Room JF 215C, Boston, Massachusetts 02115, USA
    Am J Gastroenterol 104:2047-56. 2009
    ..STMN1 activity is influenced by p53, p27, and the PI3K/AKT pathway. However, its prognostic significance in colon cancer is uncertain...
  49. pmc Aspirin use and survival after diagnosis of colorectal cancer
    Andrew T Chan
    Gastrointestinal Unit, Massachusetts General Hospital and Harvard Medical School, 55 Fruit St, GRJ 722 Boston, MA 02114, USA
    JAMA 302:649-58. 2009
    ..Aspirin reduces risk of colorectal neoplasia in randomized trials and inhibits tumor growth and metastases in animal models. However, the influence of aspirin on survival after diagnosis of colorectal cancer is unknown...
  50. pmc Prospective study of predictors of vitamin D status and survival in patients with colorectal cancer
    K Ng
    Department of Medical Oncology, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA
    Br J Cancer 101:916-23. 2009
    ....
  51. pmc Interaction of molecular markers and physical activity on mortality in patients with colon cancer
    Jeffrey A Meyerhardt
    Dana Farber Cancer Institute, Boston, MA 02115, USA
    Clin Cancer Res 15:5931-6. 2009
    ..Physical activity in colon cancer survivors has been associated with lower cancer recurrences and improved survival. Whether molecular features of the tumor portend more or less likelihood for benefit from exercise is unknown...
  52. pmc Physical activity and male colorectal cancer survival
    Jeffrey A Meyerhardt
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA, USA
    Arch Intern Med 169:2102-8. 2009
    ..Although physically active individuals have a lower risk of developing colorectal cancer, few studies have examined whether exercise benefits colorectal cancer survivors...
  53. pmc PTGER2 overexpression in colorectal cancer is associated with microsatellite instability, independent of CpG island methylator phenotype
    Yoshifumi Baba
    Department of Medical Oncology, Dana FarberCancer Institute and Harvard Medical School, Boston, Massachusetts, USA
    Cancer Epidemiol Biomarkers Prev 19:822-31. 2010
    ..However, the prognostic significance of PTGER2 expression or its relationship with MSI, CIMP, LINE-1 hypomethylation, or PTGS2 (COX-2) remains uncertain...
  54. pmc HIF1A overexpression is associated with poor prognosis in a cohort of 731 colorectal cancers
    Yoshifumi Baba
    Department of Medical Oncology, Dana Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA
    Am J Pathol 176:2292-301. 2010
    ..039). In conclusion, HIF1A expression is independently associated with poor prognosis in colorectal cancer, suggesting HIF1A as a biomarker with potentially important therapeutic implications...
  55. pmc Circulating levels of vitamin D and colon and rectal cancer: the Physicians' Health Study and a meta-analysis of prospective studies
    Jung Eun Lee
    Department of Food and Nutrition, Sookmyung Women s University, Seoul, Republic of Korea
    Cancer Prev Res (Phila) 4:735-43. 2011
    ..77; 95% CI, 0.56-1.07; P value for difference between colon and rectal cancer = 0.20). These data suggest an inverse association between circulating 25(OH)D levels and colorectal cancer, with a stronger association for rectal cancer...
  56. pmc Reported behavior of eating anything at anytime and risk of colorectal cancer in women
    Ying Bao
    Channing Laboratory, Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    Int J Cancer 130:1395-400. 2012
    ..05). In conclusion, reports of eating anything at anytime are associated with an increased risk of colorectal cancer in this large prospective cohort study, independent of other potential risk factors for colorectal cancer...
  57. pmc Relationship between statin use and colon cancer recurrence and survival: results from CALGB 89803
    Kimmie Ng
    Department of Medical Oncology, Dana Farber Cancer Institute, 450 Brookline Ave, Boston, MA 02215, USA
    J Natl Cancer Inst 103:1540-51. 2011
    ..Although preclinical and epidemiological data suggest that statins may have antineoplastic properties, the impact of statin use on patient survival after a curative resection of stage III colon cancer is unknown...
  58. pmc Cholelithiasis and the risk of nephrolithiasis
    Eric N Taylor
    Channing Laboratory, Department of Medicine, Brigham and Women s Hospital, Boston, Massachusetts 04102, USA
    J Urol 186:1882-7. 2011
    ..Therefore, we determined whether symptomatic radiographically confirmed gallstones (and/or cholecystectomy) and symptomatic kidney stone disease are independently associated...
  59. pmc The influence of UGT1A6 variants and aspirin use in a randomized trial of celecoxib for prevention of colorectal adenoma
    Andrew T Chan
    Gastrointestinal Unit, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA
    Cancer Prev Res (Phila) 5:61-72. 2012
    ..However, discontinuing celecoxib among aspirin-using individuals who initially developed adenoma despite a UGT1A6 variant genotype resulted in rapid reemergence of disease...
  60. pmc Aspirin in the chemoprevention of colorectal neoplasia: an overview
    Andrew T Chan
    Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, 55 Fruit St, Boston, MA 02114, USA
    Cancer Prev Res (Phila) 5:164-78. 2012
    ..The optimal dose to use for cancer prevention and the precise mechanism underlying aspirin's anticancer effect require further investigation...
  61. pmc Aspirin for the prevention of colorectal cancer
    X Garcia-Albeniz
    Department of Epidemiology, Harvard School of Public Health, 677 Huntington Ave, Boston, MA 02114, USA
    Best Pract Res Clin Gastroenterol 25:461-72. 2011
    ..In this review, we will summarize human studies of aspirin in CRC prevention as well as discuss the safety profile and mechanism of aspirin in CRC prevention...
  62. pmc Higher predicted vitamin D status is associated with reduced risk of Crohn's disease
    Ashwin N Ananthakrishnan
    Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02214, USA
    Gastroenterology 142:482-9. 2012
    ..Vitamin D influences innate immunity, which is believed to be involved in the pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC). However, data examining vitamin D status in relation to risk of CD and UC are lacking...
  63. pmc Geographical variation and incidence of inflammatory bowel disease among US women
    Hamed Khalili
    Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA
    Gut 61:1686-92. 2012
    ..However, there are no comparable data in the USA. The incidence of CD and UC in relation to latitude was assessed in a geographically diverse population of women enrolled in two large prospective studies in the USA...
  64. pmc Use of proton pump inhibitors and risk of hip fracture in relation to dietary and lifestyle factors: a prospective cohort study
    Hamed Khalili
    Gastroenterology Unit, Massachusetts General Hospital, Boston, MA 02114, USA
    BMJ 344:e372. 2012
    ..To examine the association between chronic use of proton pump inhibitors (PPIs) and risk of hip fracture...
  65. pmc C-reactive protein and risk of colorectal adenoma according to celecoxib treatment
    Andrew T Chan
    Gastrointestinal Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
    Cancer Prev Res (Phila) 4:1172-80. 2011
    ..Patients with low hsCRP may be a subgroup with a favorable risk-benefit profile for celecoxib chemoprevention...
  66. pmc Association of CTNNB1 (beta-catenin) alterations, body mass index, and physical activity with survival in patients with colorectal cancer
    Teppei Morikawa
    Department of Medical Oncology, Dana Farber Cancer Institute, Brigham and Women s Hospital, Harvard Medical School, 450 Brookline Ave, Boston, MA 02215, USA
    JAMA 305:1685-94. 2011
    ..Alterations of the WNT signaling pathway and cadherin-associated protein β 1 (CTNNB1 or β-catenin) have been implicated in colorectal carcinogenesis and metabolic diseases...
  67. pmc Long-term use of aspirin and the risk of gastrointestinal bleeding
    Edward S Huang
    Gastrointestinal Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
    Am J Med 124:426-33. 2011
    ..In short-term trials, aspirin is associated with gastrointestinal bleeding. However, the effect of dose and duration of aspirin use on risk remains unclear...
  68. pmc Aspirin and familial adenomatous polyposis: coming full circle
    Andrew T Chan
    Massachusetts General Hospital, Department of Medicine, Gastrointestinal Unit, Boston, MA 02114, USA
    Cancer Prev Res (Phila) 4:623-7. 2011
    ....
  69. pmc Aspirin use, body mass index, physical activity, plasma C-peptide, and colon cancer risk in US health professionals
    Xuehong Zhang
    Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA
    Am J Epidemiol 174:459-67. 2011
    ..10) for the low and 0.65 (95% CI: 0.46, 0.92) for the high group. Reductions in colon cancer risk associated with aspirin use were not significantly modified by body mass index, physical activity, or plasma C-peptide level in this study...
  70. pmc Statin use and colorectal cancer risk according to molecular subtypes in two large prospective cohort studies
    Jung Eun Lee
    Department of Food and Nutrition, Sookmyung Women s University, Seoul, Korea
    Cancer Prev Res (Phila) 4:1808-15. 2011
    ..Current statin use was not associated with risk of overall colorectal cancer. The possibility that statin use may be associated with lower risk of rectal cancer or KRAS wild-type colorectal cancer requires further confirmation...
  71. pmc Meta-analysis of new genome-wide association studies of colorectal cancer risk
    Ulrike Peters
    Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, USA
    Hum Genet 131:217-34. 2012
    ..03; combined p value 1.9 × 10(-4)). Our study suggests a complex nature of the contribution of common genetic variants to risk for colorectal cancer...
  72. pmc Cytochrome P450 2C9 variants influence response to celecoxib for prevention of colorectal adenoma
    Andrew T Chan
    Gastrointestinal Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA
    Gastroenterology 136:2127-2136.e1. 2009
    ..We examined the influence of CYP2C9*2 (R144C) and CYP2C9*3 (I359L) variants on dose-related response or toxicity in a randomized trial of celecoxib...

Research Grants30

  1. Comparative Mechanisms of Cancer Chemoprevention
    Roderick H Dashwood; Fiscal Year: 2013
    ..This application is innovative and timely in bridging basic mechanisms, preclinical models, and human studies of epigenetics and diet. ..
  2. EPIDEMIOLOGY OF ALCOHOL PROBLEMS
    Thomas K Greenfield; Fiscal Year: 2013
    ..We plan to build research capacity in the Center and other organizations, enhance careers of new investigators, and make key findings accessible to researchers, policy makers, practitioners, and the public. ..
  3. Harvard Transdisciplinary Research in Energetics and Cancer Center
    Frank B Hu; Fiscal Year: 2013
    ..By leveraging multiple areas of expertise and different resources within and across TREC centers, we can help further build a unique national resource of energetics and cancer knowledge. ..
  4. DIETARY AND HORMONAL DETERMINANTS OF CANCER IN WOMEN
    Meir Stampfer; Fiscal Year: 2013
    ..abstract_text> ..
  5. A MULTILEVEL APPROACH TO ENERGY BALANCE AND CANCER ACROSS THE LIFECOURSE
    Graham A Colditz; Fiscal Year: 2013
    ..To address these aims, we propose four research projects and five cores that form a cohesive, transdisciplinary center focused on research, training/career development, and dissemination. ..
  6. DRUG ABUSE RESEARCH CENTER
    Solomon H Snyder; Fiscal Year: 2013
    ....
  7. Women's Health Study: Continued Follow-up
    I Min Lee; Fiscal Year: 2013
    ..1 ..
  8. Intestinal Microbiota, Diet and Risk of Colorectal Adenomas
    Robert S Sandler; Fiscal Year: 2013
    ..The findings from this study could help identify individuals at high risk of adenomas as well as enhance the development of strategies to manipulate the intestinal microbiota to prevent colorectal adenomas and cancer ..
  9. NEW MODALITIES FOR TREATMENT OF PAIN AND DRUG ABUSE
    Victor J Hruby; Fiscal Year: 2013
    ....
  10. Hopkins Center for Eliminate Cardiovascular Health Disparities
    Lisa A Cooper; Fiscal Year: 2013
    ..abstract_text> ..
  11. Personalized Prevention of Colorectal Cancer
    Chang Yu; Fiscal Year: 2013
    ....
  12. Established Investigator Award Anti-Inflammatory Exposures in Cancer Prevention
    Emily White; Fiscal Year: 2013
    ..To accomplish this, the applicant will reduce her large administrative responsibilities, including stepping down from her role as Associate Dean for Research in the University of Washington School of Public Health. ..
  13. Risk Factors for Barrett's Esophagus
    Brian C Jacobson; Fiscal Year: 2013
    ....
  14. Role of Vitamin D, Inflammation, and Energy Balance in Colorectal Cancer Survival
    Kimmie Ng; Fiscal Year: 2013
    ....
  15. Penn TREC Survivor Center
    Kathryn H Schmitz; Fiscal Year: 2013
    ..abstract_text> ..