Diet, Genetic Susceptibility and Colorectal Neoplasia

Summary

Principal Investigator: Loic Le Marchand
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.
Funding Period: 1997-09-19 - 2009-07-31
more information: NIH RePORT

Top Publications

  1. pmc Variations in bitter-taste receptor genes, dietary intake, and colorectal adenoma risk
    Susan M Schembre
    a Department of Behavioral Science, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
    Nutr Cancer 65:982-90. 2013
  2. ncbi Heterocyclic amine intake, smoking, cytochrome P450 1A2 and N-acetylation phenotypes, and risk of colorectal adenoma in a multiethnic population
    Jenna Voutsinas
    Epidemiology Program, University of Hawaii Cancer Center, 1236 Lauhala Street, Suite 407, Honolulu, HI 96813, USA
    Gut 62:416-22. 2013
  3. pmc Metabolism and biomarkers of heterocyclic aromatic amines in molecular epidemiology studies: lessons learned from aromatic amines
    Robert J Turesky
    Division of Environmental Health Sciences, Wadsworth Center, Albany, New York 12201, United States
    Chem Res Toxicol 24:1169-214. 2011
  4. ncbi Association of plasma vitamin B6 with risk of colorectal adenoma in a multiethnic case-control study
    Loic Le Marchand
    Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, 96813, USA
    Cancer Causes Control 22:929-36. 2011
  5. pmc Genetic variation in the bioactivation pathway for polycyclic hydrocarbons and heterocyclic amines in relation to risk of colorectal neoplasia
    Hansong Wang
    Epidemiology Program, Cancer Research Center of Hawaii, University of Hawaii, Honolulu, HI 96813, USA
    Carcinogenesis 32:203-9. 2011
  6. pmc Generalizability and epidemiologic characterization of eleven colorectal cancer GWAS hits in multiple populations
    Jing He
    Department of Preventive Medicine, Keck School of Medicine, University of Southern California, USC Norris Comprehensive Cancer Center, Harlyne Norris Research Tower, 1450 Biggy Street, Los Angeles, CA 90033, USA
    Cancer Epidemiol Biomarkers Prev 20:70-81. 2011
  7. pmc Associations of plasma C-peptide and IGFBP-1 levels with risk of colorectal adenoma in a multiethnic population
    Loic Le Marchand
    Epidemiology Program, Cancer Research Center of Hawaii, University of Hawaii, Honolulu, HI 96813, USA
    Cancer Epidemiol Biomarkers Prev 19:1471-7. 2010
  8. ncbi Serum CRP and IL-6, genetic variants and risk of colorectal adenoma in a multiethnic population
    Simona Ognjanovic
    Epidemiology Program, Cancer Research Center of Hawaii, University of Hawaii, Honolulu, HI 96813, USA
    Cancer Causes Control 21:1131-8. 2010
  9. ncbi Association of genetic variation in the transforming growth factor beta-1 gene with serum levels and risk of colorectal neoplasia
    Barbara S Saltzman
    Epidemiology Program, Cancer Research Center of Hawaii, University of Hawaii, Honolulu, HI 96813, USA
    Cancer Res 68:1236-44. 2008
  10. doi Design considerations for genomic association studies: importance of gene-environment interactions
    Loic Le Marchand
    Epidemiology Program, Cancer Research Center of Hawaii, University of Hawaii, Suite 407, 1236 Lauhala Street, Honolulu, HI 96813, USA
    Cancer Epidemiol Biomarkers Prev 17:263-7. 2008

Scientific Experts

Detail Information

Publications14

  1. pmc Variations in bitter-taste receptor genes, dietary intake, and colorectal adenoma risk
    Susan M Schembre
    a Department of Behavioral Science, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
    Nutr Cancer 65:982-90. 2013
    ..However, given the paucity of data, we cannot dismiss the possibility that these genes may influence colorectal adenoma risk in other ways, such as through impaired gastrointestinal function, particularly in subgroups of the population. ..
  2. ncbi Heterocyclic amine intake, smoking, cytochrome P450 1A2 and N-acetylation phenotypes, and risk of colorectal adenoma in a multiethnic population
    Jenna Voutsinas
    Epidemiology Program, University of Hawaii Cancer Center, 1236 Lauhala Street, Suite 407, Honolulu, HI 96813, USA
    Gut 62:416-22. 2013
    ..This study tested the hypotheses that well-done meat and cigarette smoking increase the risk of adenoma, the precursor to most colorectal cancers, especially in individuals with rapid CYP1A2 and rapid NAT2 activities...
  3. pmc Metabolism and biomarkers of heterocyclic aromatic amines in molecular epidemiology studies: lessons learned from aromatic amines
    Robert J Turesky
    Division of Environmental Health Sciences, Wadsworth Center, Albany, New York 12201, United States
    Chem Res Toxicol 24:1169-214. 2011
    ..Lastly, the analytical approaches that have been successfully employed to biomonitor aromatic amines and HAAs, and emerging biomarkers of HAAs that may be implemented in molecular epidemiology studies are discussed...
  4. ncbi Association of plasma vitamin B6 with risk of colorectal adenoma in a multiethnic case-control study
    Loic Le Marchand
    Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, 96813, USA
    Cancer Causes Control 22:929-36. 2011
    ..This study expands previous findings and suggests that vitamin B6 may be protective against the early stages of colorectal carcinogenesis...
  5. pmc Genetic variation in the bioactivation pathway for polycyclic hydrocarbons and heterocyclic amines in relation to risk of colorectal neoplasia
    Hansong Wang
    Epidemiology Program, Cancer Research Center of Hawaii, University of Hawaii, Honolulu, HI 96813, USA
    Carcinogenesis 32:203-9. 2011
    ..This study suggests that the genomic region around ARNT rs12410394 may harbor variants associated with CRC...
  6. pmc Generalizability and epidemiologic characterization of eleven colorectal cancer GWAS hits in multiple populations
    Jing He
    Department of Preventive Medicine, Keck School of Medicine, University of Southern California, USC Norris Comprehensive Cancer Center, Harlyne Norris Research Tower, 1450 Biggy Street, Los Angeles, CA 90033, USA
    Cancer Epidemiol Biomarkers Prev 20:70-81. 2011
    ..Genome-wide association studies (GWAS) in populations of European ancestry have identified several loci that confer an increased risk of colorectal cancer (CRC)...
  7. pmc Associations of plasma C-peptide and IGFBP-1 levels with risk of colorectal adenoma in a multiethnic population
    Loic Le Marchand
    Epidemiology Program, Cancer Research Center of Hawaii, University of Hawaii, Honolulu, HI 96813, USA
    Cancer Epidemiol Biomarkers Prev 19:1471-7. 2010
    ..Circulating levels of insulin and insulin-like growth factor (IGF) hormones have been associated with colorectal cancer risk, but few studies have examined their associations with colorectal adenoma...
  8. ncbi Serum CRP and IL-6, genetic variants and risk of colorectal adenoma in a multiethnic population
    Simona Ognjanovic
    Epidemiology Program, Cancer Research Center of Hawaii, University of Hawaii, Honolulu, HI 96813, USA
    Cancer Causes Control 21:1131-8. 2010
    ....
  9. ncbi Association of genetic variation in the transforming growth factor beta-1 gene with serum levels and risk of colorectal neoplasia
    Barbara S Saltzman
    Epidemiology Program, Cancer Research Center of Hawaii, University of Hawaii, Honolulu, HI 96813, USA
    Cancer Res 68:1236-44. 2008
    ..These results suggest that a haplotype containing SNP rs11466345 at the 3' end of TGFB1 is associated with genetic susceptibility to colorectal neoplasia...
  10. doi Design considerations for genomic association studies: importance of gene-environment interactions
    Loic Le Marchand
    Epidemiology Program, Cancer Research Center of Hawaii, University of Hawaii, Suite 407, 1236 Lauhala Street, Honolulu, HI 96813, USA
    Cancer Epidemiol Biomarkers Prev 17:263-7. 2008
  11. ncbi Smoking and colorectal cancer: different effects by type of cigarettes?
    Margreet Lüchtenborg
    Epidemiology Program, Cancer Research Center of Hawaii, University of Hawaii, 1236 Lauhala Street, Suite 407, Honolulu, HI 96813, USA
    Cancer Epidemiol Biomarkers Prev 16:1341-7. 2007
    ..The data from this large study corroborate previous reports of a positive association between smoking and colorectal cancer and suggest that the association may vary by type of cigarette...
  12. pmc A common genetic risk factor for colorectal and prostate cancer
    Christopher A Haiman
    Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA
    Nat Genet 39:954-6. 2007
    ..Comprehensive testing in the region uncovered variants capturing significant additional risk. Our results show that variants at 8q24 have different effects on cancer development that depend on the tissue type...
  13. ncbi NAT2, meat consumption and colorectal cancer incidence: an ecological study among 27 countries
    Simona Ognjanovic
    Epidemiology Program, Cancer Research Center of Hawaii, 1236 Lauhala Street, Suite 407, Honolulu, HI 96813, USA
    Cancer Causes Control 17:1175-82. 2006
    ..These data suggest that, in combination with meat intake, some proportion of the international variability in CRC incidence may be attributable to genetic susceptibility to heterocyclic amines, as determined by NAT2 genotype...
  14. ncbi The predominance of the environment over genes in cancer causation: implications for genetic epidemiology
    Loic Le Marchand
    Cancer Research Center of Hawaii, University of Hawaii, 1236 Lauhala Street, Suite 407, Honolulu, HI 96813, USA
    Cancer Epidemiol Biomarkers Prev 14:1037-9. 2005