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.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
Project #
Application #
Study Section
Epidemiology and Disease Control Subcommittee 2 (EDC)
Program Officer
Patel, Appasaheb1 R
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Hawaii
Organized Research Units
United States
Zip Code
Voutsinas, Jenna; Wilkens, Lynne R; Franke, Adrian et al. (2013) Heterocyclic amine intake, smoking, cytochrome P450 1A2 and N-acetylation phenotypes, and risk of colorectal adenoma in a multiethnic population. Gut 62:416-22
Schembre, Susan M; Cheng, Iona; Wilkens, Lynne R et al. (2013) Variations in bitter-taste receptor genes, dietary intake, and colorectal adenoma risk. Nutr Cancer 65:982-90
Le Marchand, Loïc; Wang, Hansong; Selhub, Jacob et al. (2011) Association of plasma vitamin B6 with risk of colorectal adenoma in a multiethnic case-control study. Cancer Causes Control 22:929-36
Turesky, Robert J; Le Marchand, Loic (2011) Metabolism and biomarkers of heterocyclic aromatic amines in molecular epidemiology studies: lessons learned from aromatic amines. Chem Res Toxicol 24:1169-214
Wang, Hansong; Yamamoto, Jennifer F; Caberto, Christian et al. (2011) Genetic variation in the bioactivation pathway for polycyclic hydrocarbons and heterocyclic amines in relation to risk of colorectal neoplasia. Carcinogenesis 32:203-9
He, Jing; Wilkens, Lynne R; Stram, Daniel O et al. (2011) Generalizability and epidemiologic characterization of eleven colorectal cancer GWAS hits in multiple populations. Cancer Epidemiol Biomarkers Prev 20:70-81
Ognjanovic, Simona; Yamamoto, Jennifer; Saltzman, Barbara et al. (2010) Serum CRP and IL-6, genetic variants and risk of colorectal adenoma in a multiethnic population. Cancer Causes Control 21:1131-8
Le Marchand, Loic; Wang, Hansong; Rinaldi, Sabina et al. (2010) Associations of plasma C-peptide and IGFBP-1 levels with risk of colorectal adenoma in a multiethnic population. Cancer Epidemiol Biomarkers Prev 19:1471-7
Saltzman, Barbara S; Yamamoto, Jennifer F; Decker, Robert et al. (2008) Association of genetic variation in the transforming growth factor beta-1 gene with serum levels and risk of colorectal neoplasia. Cancer Res 68:1236-44
Le Marchand, Loic; Wilkens, Lynne R (2008) Design considerations for genomic association studies: importance of gene-environment interactions. Cancer Epidemiol Biomarkers Prev 17:263-7

Showing the most recent 10 out of 19 publications