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Grant Details

Grant Number: 5R01CA072520-09 Interpret this number
Primary Investigator: Le Marchand, Loic
Organization: University Of Hawaii At Manoa
Project Title: Diet, Genetic Susceptibility and Colorectal Neoplasia
Fiscal Year: 2006


Abstract

DESCRIPTION (provided by applicant): Smoking, overnutrition and a high red meat and low folate and calcium diet have been associated with colorectal cancer (CRC) and adenoma. The epidemiologic features of CRC among migrants and native populations in Hawaii suggest the modifying effects of genetic susceptibility factors on most of these associations. Taking advantage of the genetic and dietary diversity of our population, we have made good progress in investigating specific gene variants that affect one's capacity to bioactivate dietary carcinogens or utilize one-carbon groups for DNA synthesis or methylation. We also showed that a genetic variant associated with lower circulating IGF-I hormones may protect against colorectal neoplasia. We seek to renew grant 1 -R01-CA72520 to extend a case-control study of colorectal adenoma in order to test these gene-diet interactions in a large series of adenoma cases and controls, as well as to examine several new variants in these pathways in relation to adenoma, as well as CRC using existing samples/data from a companion study. New aims also include discovering new SNPs and mapping haplotypes in major genes related to the activation of heterocyclic amines and assessing population stratification in our subjects using random genetic markers. A diet and lifestyle questionnaire will be administered in person to another 904 new adenoma cases and 904 endoscopically normal controls (for a total study sample of 1,204 adenoma cases and 1,404 controls) frequency-matched on age, sex, race/ethnicity, date and mode of endoscopy. Usual consumption of meat and fish items prepared by high-temperature methods and doneness of meats will be assessed, in addition to estimating the total intake of energy, nutrients, and other dietary components. Subjects will be phenotyped for several P450 enzymes by caffeine challenge. A blood sample will also be collected to genotype subjects for variants in a number of genes related to growth hormones, carcinogen activation and folate metabolism. Sequencing of genes related to heterocyclic amine activation in colorectal cancer patients of Japanese, Caucasian, African American, Latino or Native Hawaiian origin will allow for the construction of haplotypes. Correlations with CYP1A2 phenotype will help to select functional haplotypes which will then be tested for associations with adenoma and colorectal cancer. Genotyping for random markers will permit to exclude residual confounding by ethnicity.



Publications

Causal Effects of Lifetime Smoking on Breast and Colorectal Cancer Risk: Mendelian Randomization Study.
Authors: Dimou N. , Yarmolinsky J. , Bouras E. , Tsilidis K.K. , Martin R.M. , Lewis S.J. , Gram I.T. , Bakker M.F. , Brenner H. , Figueiredo J.C. , 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 05; 30(5), p. 953-964.
EPub date: 2021-03-02.
PMID: 33653810
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A Combined Proteomics and Mendelian Randomization Approach to Investigate the Effects of Aspirin-Targeted Proteins on Colorectal Cancer.
Authors: Nounu A. , Greenhough A. , Heesom K.J. , Richmond R.C. , Zheng J. , Weinstein S.J. , Albanes D. , Baron J.A. , Hopper J.L. , Figueiredo J.C. , 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 03; 30(3), p. 564-575.
EPub date: 2020-12-14.
PMID: 33318029
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Identifying Novel Susceptibility Genes for Colorectal Cancer Risk From a Transcriptome-Wide Association Study of 125,478 Subjects.
Authors: Guo X. , Lin W. , Wen W. , Huyghe J. , Bien S. , Cai Q. , Harrison T. , Chen Z. , Qu C. , Bao J. , et al. .
Source: Gastroenterology, 2021 03; 160(4), p. 1164-1178.e6.
EPub date: 2020-10-12.
PMID: 33058866
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Identification of Novel Loci and New Risk Variant in Known Loci for Colorectal Cancer Risk in East Asians.
Authors: Lu Y. , Kweon S.S. , Cai Q. , Tanikawa C. , Shu X.O. , Jia W.H. , Xiang Y.B. , Huyghe J.R. , Harrison T.A. , Kim J. , 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 02; 29(2), p. 477-486.
EPub date: 2019-12-11.
PMID: 31826910
Related Citations

Heterocyclic amine intake, smoking, cytochrome P450 1A2 and N-acetylation phenotypes, and risk of colorectal adenoma in a multiethnic population.
Authors: Voutsinas J. , Wilkens L.R. , Franke A. , Vogt T.M. , Yokochi L.A. , Decker R. , Le Marchand L. .
Source: Gut, 2013 Mar; 62(3), p. 416-22.
EPub date: 2012-05-24.
PMID: 22628494
Related Citations

Variations in bitter-taste receptor genes, dietary intake, and colorectal adenoma risk.
Authors: Schembre S.M. , Cheng I. , Wilkens L.R. , Albright C.L. , Marchand L. .
Source: Nutrition and cancer, 2013; 65(7), p. 982-90.
EPub date: 2013-10-01.
PMID: 24083639
Related Citations

Metabolism and biomarkers of heterocyclic aromatic amines in molecular epidemiology studies: lessons learned from aromatic amines.
Authors: Turesky R.J. , Le Marchand L. .
Source: Chemical research in toxicology, 2011-08-15; 24(8), p. 1169-214.
EPub date: 2011-06-20.
PMID: 21688801
Related Citations

Association of plasma vitamin B6 with risk of colorectal adenoma in a multiethnic case-control study.
Authors: Le Marchand L. , Wang H. , Selhub J. , Vogt T.M. , Yokochi L. , Decker R. .
Source: Cancer causes & control : CCC, 2011 Jun; 22(6), p. 929-36.
EPub date: 2011-03-25.
PMID: 21437631
Related Citations

Genetic variation in the bioactivation pathway for polycyclic hydrocarbons and heterocyclic amines in relation to risk of colorectal neoplasia.
Authors: Wang H. , Yamamoto J.F. , Caberto C. , Saltzman B. , Decker R. , Vogt T.M. , Yokochi L. , Chanock S. , Wilkens L.R. , Le Marchand L. .
Source: Carcinogenesis, 2011 Feb; 32(2), p. 203-9.
EPub date: 2010-11-16.
PMID: 21081473
Related Citations

Generalizability and epidemiologic characterization of eleven colorectal cancer GWAS hits in multiple populations.
Authors: He J. , Wilkens L.R. , Stram D.O. , Kolonel L.N. , Henderson B.E. , Wu A.H. , Le Marchand L. , Haiman C.A. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2011 Jan; 20(1), p. 70-81.
EPub date: 2010-11-11.
PMID: 21071539
Related Citations

Serum CRP and IL-6, genetic variants and risk of colorectal adenoma in a multiethnic population.
Authors: Ognjanovic S. , Yamamoto J. , Saltzman B. , Franke A. , Ognjanovic M. , Yokochi L. , Vogt T. , Decker R. , Le Marchand L. .
Source: Cancer causes & control : CCC, 2010 Jul; 21(7), p. 1131-8.
EPub date: 2010-03-24.
PMID: 20333461
Related Citations

Associations of plasma C-peptide and IGFBP-1 levels with risk of colorectal adenoma in a multiethnic population.
Authors: Le Marchand L. , Wang H. , Rinaldi S. , Kaaks R. , Vogt T.M. , Yokochi L. , Decker R. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2010 Jun; 19(6), p. 1471-7.
EPub date: 2010-05-25.
PMID: 20501760
Related Citations

Association of genetic variation in the transforming growth factor beta-1 gene with serum levels and risk of colorectal neoplasia.
Authors: Saltzman B.S. , Yamamoto J.F. , Decker R. , Yokochi L. , Theriault A.G. , Vogt T.M. , Le Marchand L. .
Source: Cancer research, 2008-02-15; 68(4), p. 1236-44.
PMID: 18281501
Related Citations

Design considerations for genomic association studies: importance of gene-environment interactions.
Authors: Le Marchand L. , Wilkens L.R. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2008 Feb; 17(2), p. 263-7.
PMID: 18268108
Related Citations

A common genetic risk factor for colorectal and prostate cancer.
Authors: Haiman C.A. , Le Marchand L. , Yamamato J. , Stram D.O. , Sheng X. , Kolonel L.N. , Wu A.H. , Reich D. , Henderson B.E. .
Source: Nature genetics, 2007 Aug; 39(8), p. 954-6.
EPub date: 2007-07-08.
PMID: 17618282
Related Citations

Smoking and colorectal cancer: different effects by type of cigarettes?
Authors: L├╝chtenborg M. , White K.K. , Wilkens L. , Kolonel L.N. , Le Marchand L. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2007 Jul; 16(7), p. 1341-7.
PMID: 17626999
Related Citations

NAT2, meat consumption and colorectal cancer incidence: an ecological study among 27 countries.
Authors: Ognjanovic S. , Yamamoto J. , Maskarinec G. , Le Marchand L. .
Source: Cancer causes & control : CCC, 2006 Nov; 17(9), p. 1175-82.
PMID: 17006723
Related Citations

The predominance of the environment over genes in cancer causation: implications for genetic epidemiology.
Authors: Le Marchand L. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2005 May; 14(5), p. 1037-9.
PMID: 15894649
Related Citations

Association of the cyclin D1 A870G polymorphism with advanced colorectal cancer.
Authors: Le Marchand L. , Seifried A. , Lum-Jones A. , Donlon T. , Wilkens L.R. .
Source: JAMA, 2003-12-03; 290(21), p. 2843-8.
PMID: 14657069
Related Citations

Association of a common polymorphism in the human GH1 gene with colorectal neoplasia.
Authors: Le Marchand L. , Donlon T. , Seifried A. , Kaaks R. , Rinaldi S. , Wilkens L.R. .
Source: Journal of the National Cancer Institute, 2002-03-20; 94(6), p. 454-60.
PMID: 11904318
Related Citations

Feasibility of collecting buccal cell DNA by mail in a cohort study.
Authors: Le Marchand L. , Lum-Jones A. , Saltzman B. , Visaya V. , Nomura A.M. , Kolonel L.N. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2001 Jun; 10(6), p. 701-3.
PMID: 11401922
Related Citations

CYP1A1, GSTM1, and GSTP1 genetic polymorphisms and urinary 1-hydroxypyrene excretion in non-occupationally exposed individuals.
Authors: Nerurkar P.V. , Okinaka L. , Aoki C. , Seifried A. , Lum-Jones A. , Wilkens L.R. , Le Marchand L. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2000 Oct; 9(10), p. 1119-22.
PMID: 11045797
Related Citations

Effects of marinating with Asian marinades or western barbecue sauce on PhIP and MeIQx formation in barbecued beef.
Authors: Nerurkar P.V. , Le Marchand L. , Cooney R.V. .
Source: Nutrition and cancer, 1999; 34(2), p. 147-52.
PMID: 10578481
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