Publication list via PubMed

Our research group investigates the interactions between genetic and lifestyle factors responsible for the cancer risk differences that exist among ethnic groups in Hawaii, with the goal of advancing our understanding of the causes, mechanisms and prevention of cancer. This multidisciplinary effort is focusing on colorectal, lung and breast cancers.

Early work showed that migrants experienced a major shift in cancer rates in one or two generations toward the rates of their adoptive country, suggesting that the environment (i.e., lifestyle), and not the genetic make-up of an individual, plays a predominant role in determining cancer risk.  However, lifestyle clearly does not account for all of the variability in cancer risk that exists across individuals and populations. Indeed, it is generally accepted that most cancers result from the combined effect of environmental factors and common inherited susceptibilities.  However, these genetic factors and their interactions with environmental exposures remain largely unknown.  We have identified certain “epidemiological anomalies” in which there is a large gap between the expected cancer risk profile of a population, based on lifestyle exposures, and the observed risk.  For example, we were able to formally show that there remain substantial ethnic differences in lung cancer risk among ethnic populations after adjusting for smoking patterns and other risk factors.  Most interestingly, the risk associated with smoking was significantly different among ethnic groups.  Similarly, we observed that the colorectal cancer risk of Japanese migrants to Hawaii has been significantly greater than one would expect from their exposure to most risk factors and that this excess risk is likely to be of genetic origin. Finally, persisting differences in breast cancer rates and survival among ethnic groups in Hawaii suggest the possibility of genetically based differences in etiology, tumor invasiveness and/or response to treatment.  Such unexpected risk and survival patterns provide unique opportunities to identify important gene-environment interactions.

To investigate these and other intriguing epidemiological observations in our population, we established in the early 1990’s a program of research on inherited gene variants that modify the risk associated with lifestyle exposures (smoking, dietary constituents, obesity and medications).  This NCI-funded research relies on cross-sectional, case-control, cohort and intervention studies, as well as a Family Registry, and relies heavily on new information available on the human genome and, particularly, the 0.1% of bases that differ across individuals and that are responsible for phenotypic variation.  This research first focused on functional genetic polymorphisms that affect carcinogen bioactivation, DNA synthesis and repair, cell proliferation, and angiogenesis. It now includes broader investigations, such as pathway-driven and whole-genome association studies. Particular attention is given to replication, generalizability and gene-environment interactions when assessing association with disease. Molecular studies, some using microarrays, are also conducted to characterize the effects of the putative causal variants identified on gene expression or intermediate phenotypes.

Our findings to date suggest that the interactions of specific genetic and lifestyle factors play an important role in determining population and individual risks for common cancers and that Hawaii’s multiethnic population provides a fertile ground for this research.

Active Grants

L. Le Marchand, Principal Investigator
R01 CA 72520
"Diet, Genetic Susceptibility and Colorectal Neoplasia"
August 1, 1997-July 31, 2009

L. Le Marchand, Principal Investigator
R01 CA104132
"Ethnic/Racial Minorities in the Colon CFR"
September 28, 2004-June 30, 2009

L. Le Marchand, Principal Investigator
American Institute of Cancer Research Grant #06A102
"A Comparative Study of Adenoma in Brazil, Japan and Hawaii"
January 1, 2007-December 31, 2009

L. Le Marchand, Principal Investigator
R03 CA119682
"Case-Control Study of Adenoma in Sao Paulo Japanese"
July 1, 2007-June 30, 2009

R01 CA122320 (sub-contract from NYS Health Dept., Dr. Robert Turesky, PI)
"Chemical Markers of Heterocyclic Aromatic Amines for Human Biomonitoring"
September 11, 2007-July 31, 2012

U01 CA98758 (sub-contract from USC, Dr. Brian Henderson, PI)
"Characterizing Genetic Susceptibility to Breast and Prostate Cancer; the BPC3"
September 30, 2003-July 31, 2011

L. Le Marchand, Principal Investigator
U01 HG004802
"Epidemiology of Putative Causal Variants in the Multiethnic Cohort"
July 17, 2008-May 31, 2012

L. Le Marchand, Principal Investigator
R01 CA126895
"Whole Genome Scan for Modifier Genes in Colorectal Cancer"
September 1, 2008-July 31, 2013

L. Le Marchand, Co-Principal Investigator
R25 CA090956 (Co-PI with Dr. Gertraud Maskarinec)
"Nutritional & Behavioral Cancer Prevention in a Multiethnic Population"
September 1, 2008-August 31, 2013

L. Le Marchand, Principal Investigator
R01 CA129063
"Inflammation and Innate Immunity Genes and Colorectal Cancer Risk"
September 15, 2008-July 31, 2012

L. Le Marchand, Principal Investigator
U24 CA074806
"The Colon Cancer Family Registry: Hawaii"
September 24, 1998-August 31, 2012

L. Kolonel, Principal Investigator
L. Le Marchand, Project Leader, Core Leader
P01 CA 033619
"Epidemiologic Studies of Diet and Cancer in Hawai‘i
July 1, 2000-June 30, 2009