NUTRITIONAL AND BIOCHEMICAL/GENETIC MARKERS OF CANCER

Summary

Principal Investigator: J Ma
Abstract: DESCRIPTION (provided by applicant): We propose to extend our on-going studies of nutritional and biochemical/genetic markers of colorectal and prostate cancer in the Physicians' Health Study (PHS). Over the past 10 years, we have made major contributions in the field of insulin-like growth factor (IGF)-I and its binding protein (IGFBP)-3, folate and the MTHFR polymorphism, vitamin D metabolites and vitamin D receptor (VDR) polymorphisms and carcinogenesis. We plan to build upon these findings in the next 5 years using a prospective nested case-control study design. Specifically, we plan to extend the IGF hypothesis to assess the role of growth hormone (GH)/IGF/insulin-related biochemical markers in colorectal and prostate cancer. These markers include GH, acid labile subunit (ALS, a third component of the ternary complex with IGF-I and IGFBP-3 in circulation), C-peptide (a marker of insulin secretion), leptin (a marker of total body fat and energy balance), interleukin (IL)-6 and C-reactive protein (CRP) (inflammatory cytokines linked to obesity and insulin resistance). We also plan to extend the folate hypothesis to assess the role of pyridoxal 5'-phosphate (PLP), the principal active form of vitamin B6, and homocysteine along the one-carbon metabolism pathway in risk of colorectal cancer. We will evaluate the roles of several common polymorphisms recently identified in the key GH/IGF-I/insulin signaling pathway, in nuclear hormone receptors, and in the folate metabolic pathway. These include polymorphisms in genes encoding the following proteins: the GH1, insulin receptor substrate (IRS)-1, IRS-2, posphatidylinositol 3'- kinase (PI3K)-p85 subunit, peroxisome proliferator-activated receptor (PPARgamma, a nuclear hormone receptor that plays a key role in adipocyte differentiation), VDR (FokI), IL-6, methionine syntheses reductase (MTRR), and reduced folate carrier (RFC-1). We will evaluate whether these polymorphisms modify the associations of circulating levels of biochemical markers with cancer risk. We will explore potential interactions between IGF-I, IGFBP-3 and vitamin D metabolites and VDR polymorphisms. The PHS originated in 1982 with two decades of follow-up of 14,916 men who provided blood samples at baseline. In 1995, we collected a baseline blood sample from 5,805 new participants. We project a total of 1,902 prostate cancer cases, and 369 colorectal cancer cases, providing reasonably good statistical power. The blood samples are already collected, and several biochemical markers (IGF-I, IGFBP-3, vitamin D metabolites, and folate) and polymorphisms (VDR BsmI and MTHFR C677T) are already assayed for many of the samples (cases and controls identified up to 2000). Hence, the proposed project is highly cost-efficient.
Funding Period: 1986-06-01 - 2010-06-30
more information: NIH RePORT

Top Publications

  1. pmc A prospective study of dietary folate and vitamin B and colon cancer according to microsatellite instability and KRAS mutational status
    Eva S Schernhammer
    Channing Laboratory, Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    Cancer Epidemiol Biomarkers Prev 17:2895-8. 2008
  2. pmc Genetic variation across C-reactive protein and risk of prostate cancer
    Sarah C Markt
    Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts
    Prostate 74:1034-42. 2014
  3. pmc A 22-y prospective study of fish intake in relation to prostate cancer incidence and mortality
    Jorge E Chavarro
    Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA
    Am J Clin Nutr 88:1297-303. 2008
  4. 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
  5. pmc Selenoprotein P genetic variants and mrna expression, circulating selenium, and prostate cancer risk and survival
    Kathryn L Penney
    Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA
    Prostate 73:700-5. 2013
  6. pmc Whole milk intake is associated with prostate cancer-specific mortality among U.S. male physicians
    Yan Song
    Department of Epidemiology and Program on Genomics and Nutrition, Fielding School of Public Health, University of California Los Angeles, Los Angeles, CA, USA
    J Nutr 143:189-96. 2013
  7. pmc A prospective study of plasma vitamin D metabolites, vitamin D receptor gene polymorphisms, and risk of hypertension in men
    Lu Wang
    Division of Preventive Medicine, Department of Medicine, Brigham and Women s Hospital, 900 Commonwealth Avenue East, Boston, MA, 02215, USA
    Eur J Nutr 52:1771-9. 2013
  8. pmc Genome-wide association analyses in East Asians identify new susceptibility loci for colorectal cancer
    Wei Hua Jia
    State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat Sen University, Guangzhou, China
    Nat Genet 45:191-6. 2013
  9. pmc Identification of Genetic Susceptibility Loci for Colorectal Tumors in a Genome-Wide Meta-analysis
    Ulrike Peters
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109 1024, USA
    Gastroenterology 144:799-807.e24. 2013
  10. 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

Scientific Experts

  • Olivia I Okereke
  • Esther K Wei
  • Haojie Li
  • Jennifer R Stark
  • Kathryn L Penney
  • J E Chavarro
  • Fang Fang
  • K Fall
  • M D Holmes
  • Megan N Hall
  • Jung Eun Lee
  • Anita Koushik
  • I Shai
  • L A Mucci
  • E S Schernhammer
  • Carolyn M Hutter
  • D S Michaud
  • Jing Ma
  • Ulrike Peters
  • Meir J Stampfer
  • Andrew T Chan
  • Qi Sun
  • Shuo Jiao
  • Polly A Newcomb
  • Hermann Brenner
  • Loic Le Marchand
  • Jenny Chang-Claude
  • Stephane Bezieau
  • Graham Casey
  • Martha L Slattery
  • Mathieu Lemire
  • Fredrick R Schumacher
  • Steven Gallinger
  • Tabitha A Harrison
  • Sebastien Kury
  • David V Conti
  • Charles S Fuchs
  • Emily White
  • Mark A Jenkins
  • John D Potter
  • Brent W Zanke
  • Thomas J Hudson
  • Robert E Schoen
  • Bette J Caan
  • Daniela Seminara
  • Li Hsu
  • Michael Hoffmeister
  • Richard B Hayes
  • John L Hopper
  • Peter T Campbell
  • Howard D Sesso
  • Edward Giovannucci
  • Sonja I Berndt
  • Edward L Giovannucci
  • John A Baron
  • Stephen J Chanock
  • Frank B Hu
  • Wei Hua Jia
  • Hannia Campos
  • Conghui Qu
  • Ling Hao
  • David Duggan
  • Yin Cao
  • JoAnn E Manson
  • Michael Pollak
  • Weiliang Qiu
  • Paul L Nguyen
  • Walter C Willett
  • Sarah C Markt
  • Iona Cheng
  • Peter Kraft
  • Charles Kooperberg
  • Noralane M Lindor
  • Robert W Haile
  • Wei Zheng
  • Sun Ha Jee
  • Lu Wang
  • Linda T Hiraki
  • Xiao Ou Shu
  • Yi Xin Zeng
  • Keitaro Matsuo
  • Yan Song
  • Ben Zhang
  • Christopher S Carlson
  • Keith R Curtis
  • Stephanie A Rosse
  • Rebecca D Jackson
  • Jennifer R Rider
  • Stephen B Gruber
  • Hongmei Nan

Detail Information

Publications59

  1. pmc A prospective study of dietary folate and vitamin B and colon cancer according to microsatellite instability and KRAS mutational status
    Eva S Schernhammer
    Channing Laboratory, Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    Cancer Epidemiol Biomarkers Prev 17:2895-8. 2008
    ..In conclusion, the influence of dietary one-carbon nutrient intake on colon cancer risk does not seem to differ according to MSI or KRAS mutational status...
  2. pmc Genetic variation across C-reactive protein and risk of prostate cancer
    Sarah C Markt
    Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts
    Prostate 74:1034-42. 2014
    ..We investigated the role of genetic variation in CRP and prostate cancer, under the hypothesis that variants may alter risk of disease...
  3. pmc A 22-y prospective study of fish intake in relation to prostate cancer incidence and mortality
    Jorge E Chavarro
    Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA
    Am J Clin Nutr 88:1297-303. 2008
    ..Fish and seafood n-3 fatty acids may prevent or delay the progression of prostate cancer, but epidemiologic studies do not uniformly support this hypothesis...
  4. 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...
  5. pmc Selenoprotein P genetic variants and mrna expression, circulating selenium, and prostate cancer risk and survival
    Kathryn L Penney
    Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA
    Prostate 73:700-5. 2013
    ..We examined the association of SEPP1 single nucleotide polymorphisms (SNPs) with PCa risk and survival, and tested for interactions...
  6. pmc Whole milk intake is associated with prostate cancer-specific mortality among U.S. male physicians
    Yan Song
    Department of Epidemiology and Program on Genomics and Nutrition, Fielding School of Public Health, University of California Los Angeles, Los Angeles, CA, USA
    J Nutr 143:189-96. 2013
    ..These findings add further evidence to suggest the potential role of dairy products in the development and prognosis of PCa...
  7. pmc A prospective study of plasma vitamin D metabolites, vitamin D receptor gene polymorphisms, and risk of hypertension in men
    Lu Wang
    Division of Preventive Medicine, Department of Medicine, Brigham and Women s Hospital, 900 Commonwealth Avenue East, Boston, MA, 02215, USA
    Eur J Nutr 52:1771-9. 2013
    ..Evidence from epidemiologic studies remains limited. We aim to examine the prospective associations of circulating vitamin D metabolites, vitamin D receptor (VDR) gene polymorphisms, and their interaction with risk of hypertension...
  8. pmc Genome-wide association analyses in East Asians identify new susceptibility loci for colorectal cancer
    Wei Hua Jia
    State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat Sen University, Guangzhou, China
    Nat Genet 45:191-6. 2013
    ..This study identified three new CRC susceptibility loci and provides additional insight into the genetics and biology of CRC...
  9. pmc Identification of Genetic Susceptibility Loci for Colorectal Tumors in a Genome-Wide Meta-analysis
    Ulrike Peters
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109 1024, USA
    Gastroenterology 144:799-807.e24. 2013
    ..Heritable factors contribute to the development of colorectal cancer. Identifying the genetic loci associated with colorectal tumor formation could elucidate the mechanisms of pathogenesis...
  10. 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...
  11. pmc Pleiotropic effects of genetic risk variants for other cancers on colorectal cancer risk: PAGE, GECCO and CCFR consortia
    Iona Cheng
    Cancer Prevention Institute of California, Fremont, California, USA
    Gut 63:800-7. 2014
    ..In a large-scale study, we examined 171 SNPs previously associated with 18 different cancers for their associations with colorectal cancer...
  12. pmc SBERIA: set-based gene-environment interaction test for rare and common variants in complex diseases
    Shuo Jiao
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA
    Genet Epidemiol 37:452-64. 2013
    ....
  13. pmc Genome-wide search for gene-gene interactions in colorectal cancer
    Shuo Jiao
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America
    PLoS ONE 7:e52535. 2012
    ..1) (nominal combined p = 2.51×10(-6); Bonferroni adjusted p = 0.03). Our study represents the first comprehensive search for GxG in CRC, and our results may provide new insight into the genetic etiology of CRC...
  14. pmc Fasting plasma insulin, C-peptide and cognitive change in older men without diabetes: results from the Physicians' Health Study II
    Olivia I Okereke
    Divisions of Aging, Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    Neuroepidemiology 34:200-7. 2010
    ..We examined prospectively relations of fasting insulin levels and insulin secretion to cognitive decline among healthy, community-dwelling older men without diabetes...
  15. pmc A large prospective study of SEP15 genetic variation, interaction with plasma selenium levels, and prostate cancer risk and survival
    Kathryn L Penney
    Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA
    Cancer Prev Res (Phila) 3:604-10. 2010
    ..Additionally, the association of selenium with PCa mortality was modified by a variant, suggesting the possibility that some men with PCa may benefit more from selenium than others, depending on their genotype...
  16. pmc Fatty acid synthase polymorphisms, tumor expression, body mass index, prostate cancer risk, and survival
    Paul L Nguyen
    Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
    J Clin Oncol 28:3958-64. 2010
    ..We examined whether common germline single nucleotide polymorphisms (SNPs) in the FASN gene affect prostate cancer (PCa) risk or PCa-specific mortality and whether these effects vary by body mass index (BMI)...
  17. pmc Body mass index, prostate cancer-specific mortality, and biochemical recurrence: a systematic review and meta-analysis
    Yin Cao
    Channing Laboratory, Department of Medicine, Brigham and Women s Hospital, Boston, MA 02115, USA
    Cancer Prev Res (Phila) 4:486-501. 2011
    ..Its association with prostate cancer-specific mortality in diagnosed patients needs to be further evaluated...
  18. pmc Association of KLK3 (PSA) genetic variants with prostate cancer risk and PSA levels
    Kathryn L Penney
    Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA
    Carcinogenesis 32:853-9. 2011
    ..Understanding the mechanism by which genetic variation in KLK3 affects prostate cancer risk has important implications for study of the biological role of PSA in prostate tumorigenesis...
  19. 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...
  20. pmc Prediagnostic plasma vitamin D metabolites and mortality among patients with prostate cancer
    Fang Fang
    Channing Laboratory, Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts, United States of America
    PLoS ONE 6:e18625. 2011
    ..Laboratory evidence suggests that vitamin D might influence prostate cancer prognosis...
  21. pmc Common polymorphisms in the adiponectin and its receptor genes, adiponectin levels and the risk of prostate cancer
    Preet K Dhillon
    Channing Laboratory, Brigham and Women s Hospital and Harvard Medical School Boston, MA, USA
    Cancer Epidemiol Biomarkers Prev 20:2618-27. 2011
    ..However, the role of genetic variation in the adiponectin (ADIPOQ) and receptor genes (ADIPOR1/R2) in prostate cancer is largely unknown...
  22. 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
    ....
  23. pmc Plasma folate, methylenetetrahydrofolate reductase (MTHFR), and colorectal cancer risk in three large nested case-control studies
    Jung Eun Lee
    Department of Food and Nutrition, Sookmyung Women s University, Seoul, Korea
    Cancer Causes Control 23:537-45. 2012
    ..The reasons underlying a lower risk of colorectal cancer with low plasma folate levels require elucidation because plasma folate levels can reflect dietary intake, genetic influences, and other factors...
  24. pmc No association between a polymorphic variant of the IRS-1 gene and prostate cancer risk
    K Fall
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
    Prostate 68:1416-20. 2008
    ..We assessed the influence of the most common IRS-1 gene polymorphism (Gly972Arg) on prostate cancer risk, alone and in combination with IGF-1 and other components in the IGF-1 signaling pathway...
  25. ncbi Vitamin B-12 deficiency is prevalent in 35- to 64-year-old Chinese adults
    Ling Hao
    Institute of Reproductive and Child Health, Peking University, Beijing, 100083, China
    J Nutr 137:1278-85. 2007
    ..Further studies are needed to evaluate the health effects and possible intervention strategies in areas where B-12 vitamin deficiency is common...
  26. ncbi A prospective study of trans fatty acids in erythrocytes and risk of coronary heart disease
    Qi Sun
    Department of Nutrition, Harvard School of Public Health, 665 Huntington Ave, Boston, MA 02115, USA
    Circulation 115:1858-65. 2007
    ..We assessed the hypothesis that higher trans fatty acid contents in erythrocytes were associated with an elevated risk of CHD in a nested case-control study among US women...
  27. pmc A prospective study of plasma vitamin D metabolites, vitamin D receptor polymorphisms, and prostate cancer
    Haojie Li
    Channing Laboratory, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts, United States of America
    PLoS Med 4:e103. 2007
    ..Few studies have explored the joint association of circulating vitamin D levels with VDR polymorphisms...
  28. ncbi Validation of a food frequency questionnaire measurement of selected nutrients using biological markers in African-American men
    M D Holmes
    Channing Laboratory, Department of Medicine, Harvard Medical School and Brigham and Women s Hospital, Boston, MA, USA
    Eur J Clin Nutr 61:1328-36. 2007
    ..To validate selected nutrients assessed by the food frequency questionnaire (FFQ) used in the Harvard cohort studies in an African-American group...
  29. ncbi High prevalence of hyperhomocysteinemia in Chinese adults is associated with low folate, vitamin B-12, and vitamin B-6 status
    Ling Hao
    Institute of Reproductive and Child Health, Peking University, Beijing 100083, China, and Channing Laboratory, Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    J Nutr 137:407-13. 2007
    ..Low plasma concentrations of folate, vitamins B-12 and B-6, older age, being male, and living in urban areas were all independently associated with elevated tHcy, with low folate as the strongest determinant...
  30. ncbi Vitamin and mineral supplements for cancer prevention: issues and evidence
    Kathleen Fairfield
    Department of Medicine, Maine Medical Center, Portland, ME, USA
    Am J Clin Nutr 85:289S-292S. 2007
    ....
  31. ncbi Plasma C-peptide and cognitive performance in older men without diabetes
    Olivia Okereke
    Division of Aging, Department of Medicine, Brigham and Women s Hospital, and Harvard Medical School, Boston, MA, USA
    Am J Geriatr Psychiatry 14:1041-50. 2006
    ..Emerging evidence suggests that type 2 diabetes may be related to diminished cognition, but little data are available directly regarding the role of insulin levels...
  32. ncbi Midlife plasma insulin-like growth factor I and cognitive function in older men
    Olivia I Okereke
    Division of Aging, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Clin Endocrinol Metab 91:4306-12. 2006
    ..Emerging biological and epidemiological evidence suggests possible benefits of higher IGF-I levels in cognitive aging...
  33. ncbi p53 Arg72Pro polymorphism and risk of colorectal adenoma and cancer
    Anita Koushik
    Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA
    Int J Cancer 119:1863-8. 2006
    ..09, 95% CI = 1.28-3.40) but not proximal colon or rectal cancers. Our results suggest that Arg72Pro may play a role in the early stages of colorectal neoplasia and possibly in progression to invasive disease, depending on site and sex...
  34. ncbi C-peptide, insulin-like growth factor binding protein-1, glycosylated hemoglobin, and the risk of distal colorectal adenoma in women
    Esther K Wei
    Channing Laboratory, Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    Cancer Epidemiol Biomarkers Prev 15:750-5. 2006
    ..However, few studies have evaluated whether these factors are also associated with risk of colorectal adenoma, the main precursor lesion to colorectal cancer...
  35. ncbi Prediagnostic plasma vascular endothelial growth factor levels and risk of prostate cancer
    Haojie Li
    Channing Laboratory, Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Room 452, 181 Longwood Avenue, Boston, Massachusetts 02115, USA
    Cancer Epidemiol Biomarkers Prev 14:1557-61. 2005
    ..Our results indicate that prediagnostic circulating VEGF levels are not associated with prostate cancer development and have limited value in predicting future risk of prostate cancer...
  36. ncbi Epoxide hydrolase and CYP2C9 polymorphisms, cigarette smoking, and risk of colorectal carcinoma in the Nurses' Health Study and the Physicians' Health Study
    Gregory J Tranah
    Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA
    Mol Carcinog 44:21-30. 2005
    ..Our results indicate that individuals exposed to tobacco carcinogens were at increased risk of colorectal cancer and that overall risk is related to mEH and CYP2C9 genotype, although the results were not consistent between men and women...
  37. ncbi Plasma vitamin B6 and the risk of colorectal cancer and adenoma in women
    Esther K Wei
    Channing Laboratory, Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    J Natl Cancer Inst 97:684-92. 2005
    ..However, no previous epidemiologic studies have directly evaluated the association of plasma PLP with risk for colorectal neoplasia...
  38. ncbi A prospective study of C-peptide, insulin-like growth factor-I, insulin-like growth factor binding protein-1, and the risk of colorectal cancer in women
    Esther K Wei
    Channing Laboratory, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, 3rd Floor, 181 Longwood Avenue, Boston, MA 02115, USA
    Cancer Epidemiol Biomarkers Prev 14:850-5. 2005
    ..Although altering IGF-I levels may not be practical, the growing burden of obesity and consequently hyperinsulinemia, which seems increasingly important for colon cancer, may be a target for effective prevention...
  39. ncbi Lipoprotein (a) and coronary heart disease among women: beyond a cholesterol carrier?
    Iris Shai
    Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA
    Eur Heart J 26:1633-9. 2005
    ..We assessed the role of Lp(a) in coronary heart diseases (CHD) by a recently developed assay that is not affected by the plasminogen-like Kringle-type-2 repeats...
  40. ncbi A prospective study of polyunsaturated fatty acid levels in blood and prostate cancer risk
    Jorge E Chavarro
    Department of Nutrition, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115, USA
    Cancer Epidemiol Biomarkers Prev 16:1364-70. 2007
    ..Animal models suggest that n-3 fatty acids inhibit prostate cancer proliferation, whereas n-6 fatty acids promote it, but epidemiologic studies do not uniformly support these findings...
  41. ncbi Comparison between plasma and erythrocyte fatty acid content as biomarkers of fatty acid intake in US women
    Qi Sun
    Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA
    Am J Clin Nutr 86:74-81. 2007
    ..Erythrocyte fatty acids may be superior to plasma fatty acids for reflecting long-term fatty acid intake because of less sensitivity to recent intake and a slower turnover rate...
  42. pmc Folate and vitamin B6 intake and risk of colon cancer in relation to p53 expression
    Eva S Schernhammer
    Department of Medicine, Channing Laboratory, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    Gastroenterology 135:770-80. 2008
    ..In laboratory models, folate deficiency appears to induce p53 mutation...
  43. pmc Prediagnostic body-mass index, plasma C-peptide concentration, and prostate cancer-specific mortality in men with prostate cancer: a long-term survival analysis
    Jing Ma
    Channing Laboratory, Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, MA, USA
    Lancet Oncol 9:1039-47. 2008
    ..We assessed the effect of prediagnostic BMI and plasma C-peptide concentration (reflecting insulin secretion) on prostate cancer-specific mortality after diagnosis...
  44. ncbi Blood concentrations of individual long-chain n-3 fatty acids and risk of nonfatal myocardial infarction
    Qi Sun
    Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA
    Am J Clin Nutr 88:216-23. 2008
    ..Whereas dietary intake of long-chain n-3 fatty acids has been associated with risk of nonfatal myocardial infarction (MI), few studies have examined the relation for blood concentrations...
  45. pmc A 22-year prospective study of fish, n-3 fatty acid intake, and colorectal cancer risk in men
    Megan N Hall
    Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY 10032, USA
    Cancer Epidemiol Biomarkers Prev 17:1136-43. 2008
    ..Human studies have not shown consistent results. We examined the association between intakes of fish and n-3 fatty acids from fish and colorectal cancer risk in men enrolled in the Physicians' Health Study...
  46. pmc Circulating prediagnostic interleukin-6 and C-reactive protein and prostate cancer incidence and mortality
    Jennifer Rider Stark
    Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA
    Int J Cancer 124:2683-9. 2009
    ..02). Adjusted hazard ratios were 1.73 (95% CI: 0.86, 3.51) comparing the highest to lowest IL-6 level. Our study suggests that IL-6 may potentially be involved in the development or progression of prostate cancer...
  47. pmc Prospective study of plasma vitamin B6 and risk of colorectal cancer in men
    Jung Eun Lee
    Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    Cancer Epidemiol Biomarkers Prev 18:1197-202. 2009
    ..92 (0.55-1.56), 0.42 (0.23-0.75), and 0.49 (0.26-0.92; P(trend) = 0.01), respectively. In conclusion, vitamin B(6) may protect against colorectal cancer independent of other one-carbon metabolites and inflammatory biomarkers...
  48. pmc Polymorphism in endostatin, an angiogenesis inhibitor, and prostate cancer risk and survival: A prospective study
    Lorelei A Mucci
    Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    Int J Cancer 125:1143-6. 2009
    ..However, our data indicate that prostate cancer cases who carry the variant N allele are more likely to be overweight, and may be more susceptible to the angiogenic influences of obesity in prostate cancer pathogenesis...
  49. pmc Gleason score and lethal prostate cancer: does 3 + 4 = 4 + 3?
    Jennifer R Stark
    ScD, Department of Epidemiology, Harvard School of Public Health, 677 Huntington Ave, Boston, MA 02115, USA
    J Clin Oncol 27:3459-64. 2009
    ..82; biopsy C-statistic, 0.72). CONCLUSION Ignoring the predominance of Gleason pattern 4 in GS 7 cancers may conceal important prognostic information. A standardized review of GS can improve prediction of PCa survival...
  50. pmc Prospective study of Trichomonas vaginalis infection and prostate cancer incidence and mortality: Physicians' Health Study
    Jennifer R Stark
    Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA
    J Natl Cancer Inst 101:1406-11. 2009
    ..We confirmed these findings in an independent population and related serostatus for antibodies against T vaginalis to prostate cancer incidence and mortality...
  51. pmc A 25-year prospective study of plasma adiponectin and leptin concentrations and prostate cancer risk and survival
    Haojie Li
    GlaxoSmithKline R and D, Worldwide Epidemiology Oncology, Collegeville, PA, USA
    Clin Chem 56:34-43. 2010
    ..Adipocytokines may mediate the association between adiposity and lethal prostate cancer outcomes...
  52. ncbi Type 2 diabetes mellitus and cognitive decline in two large cohorts of community-dwelling older adults
    Olivia I Okereke
    Division of Aging and Channing Laboratory, Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    J Am Geriatr Soc 56:1028-36. 2008
    ..To relate diabetes mellitus (DM) status and duration to late-life cognitive impairment and decline in men and women...
  53. ncbi A prospective study of trans-fatty acid levels in blood and risk of prostate cancer
    Jorge E Chavarro
    Department of Nutrition, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115, USA
    Cancer Epidemiol Biomarkers Prev 17:95-101. 2008
    ..Previous studies suggest a positive association between markers of trans-fatty acid intake and prostate cancer. We therefore prospectively evaluated the association between blood trans-fatty acid levels and risk of prostate cancer...
  54. ncbi Plasma and erythrocyte biomarkers of dairy fat intake and risk of ischemic heart disease
    Qi Sun
    Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA
    Am J Clin Nutr 86:929-37. 2007
    ..The relation between dairy product intake and the risk of ischemic heart disease (IHD) remains controversial...
  55. ncbi Prediagnostic plasma C-peptide and pancreatic cancer risk in men and women
    Dominique S Michaud
    Channing Laboratory, Department of Medicine, Brigham and Women s Hospital, Boston, MA 02115, USA
    Cancer Epidemiol Biomarkers Prev 16:2101-9. 2007
    ..An association between serum insulin levels and pancreatic cancer risk was reported in a recent study, but the population was composed of heavy smokers and their findings may not be generalizable to nonsmokers...
  56. ncbi Hypoxia-inducible factor-1alpha (HIF-1alpha) gene polymorphisms, circulating insulin-like growth factor binding protein (IGFBP)-3 levels and prostate cancer
    Haojie Li
    Channing Laboratory, Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    Prostate 67:1354-61. 2007
    ....
  57. ncbi Manganese superoxide dismutase polymorphism, prediagnostic antioxidant status, and risk of clinical significant prostate cancer
    Haojie Li
    Channing Laboratory, Department of Medicine Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    Cancer Res 65:2498-504. 2005
    ..Both endogenous and exogenous antioxidants play an important and interdependent role in preventing clinically significant prostate cancer...