• Professor
  Cancer Epidemiology Program
  University of Hawaii Cancer Center
• Clinical Professor
  Public Health;
  Graduate Faculty
  Biomedical Sciences Interdisciplinary Graduate Program
  Cell and Molecular Biology Program
  John A. Burns School of Medicine, University of Hawaii at Manoa
  
• Graduate Faculty
  Department of Food Science and Human Nutrition
  College of Tropical Agriculture and Human Resources, University of Hawaii at Manoa

Degrees

• MD
  University of Rennes, France
• PhD, Epidemiology/Biostatistics, MPH, Epidemiology
  University of Hawaii at Manoa
  
• Preventive Medicine Residency
  University of Hawaii at Manoa
  
• Preventive Medicine Residency
  French Medical License and Certification in Public Health

Research Focus

The Epidemiology Program 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. The researchers have identified in Hawaii several "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, providing unique opportunities to identify potentially important gene-environment interactions.

To investigate these intriguing epidemiological observations, a research program was established in the early 1990's on inherited gene variants that modify the risk associated with lifestyle exposures (smoking, dietary constituents, obesity and medications). This NCI- and NHGRI-funded research relies on cross-sectional, case-control, cohort and intervention studies and a Family Registry. It relies heavily on new information available on the human genome and, particularly, the 0.1% of bases that differ across individuals and are responsible for phenotypic variation. This research first focused on functional genetic polymorphisms affecting 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.

Publications

• Wang H, Yamamoto J, Caberto C, Saltzman B, Decker R, Vogt TM, Yokochi L, Chanock S, Wilkens LR, Le Marchand L. Genetic variation in the bioactivation pathway for polycyclic hydrocarbons and heterocyclic amines in relation to risk of colorectal neoplasia. Carcinogenesis 2011;32(2):203-9. Epub 2010 Nov 16.
• Cheng I, Caberto CP, Lum-Jones A, Seifried A, Wilkens LR, Schumacher FR, Monroe KR, Lim U, Tiirikainen M, Kolonel LN, Henderson BE, Stram DO, Haiman CA, Le Marchand L. Associations of established Type 2 Diabetes risk variants with colorectal cancer: the Multiethnic Cohort and PAGE studies . Gut. 2011 May 20. [Epub ahead of print]
• Le Marchand L, Derby KS, Murphy SE, Hecht SS, Hatsukami D, Carmella SG, Tiirikainen M, Wang H. Smokers with the CHRNA lung cancer-associated variants are exposed to higher levels of nicotine equivalents and a carcinogenic tobacco-specific nitrosamine. Cancer Res 2008;68:9137-40.
• Poynter JN, Figueiredo JC, Conti D, Kennedy K, Gallinger S, Siegmund KD, Casey G, Thibodeau S, Jenkins M, Hopper J, Byrnes G, Baron J, Goode E, Tiirikainen M, Lindor N, Grove J, Newcomb P, Jass J, Young J, Potter J, Haile RW, Duggan DJ and Le Marchand L. Variants on 9p24 and 8q24 are associated with risk of colorectal cancer: Results from the Colon Cancer Family Registry. Cancer Res 2007;67:11128-32.

Publication list via PubMed

Active Grants

• 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, 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
  "Hawaii Colorectal Cancer Family Registry"
  September 24, 1998-August 31, 2012