Loic Le Marchand, MD, PhD

Loïc Le Marchand, MD, PhD

This email address is being protected from spambots. You need JavaScript enabled to view it. | (808) 564-5899

Associate Director for Ethnic Diversity, University of Hawaiʻi Cancer Center
Full Member, Population Sciences in the Pacific Program (Cancer Epidemiology), University of Hawaiʻi Cancer Center

Academic Appointment(s):
Professor (Researcher), Population Sciences in the Pacific Program (Cancer Epidemiology), University of Hawaiʻi Cancer Center
Clinical Professor, Public Health, John A. Burns School of Medicine, University of Hawaiʻi at Mānoa
Graduate Faculty - Office of Public Health Studies, University of Hawaiʻi at Mānoa; Human Nutrition, Food and Animal Sciences, University of Hawaiʻi at Mānoa; Biomedical Sciences - Clinical Research Track and Cell and Molecular Biology Program, John A. Burns School of Medicine, University of Hawaiʻi at Mānoa;

Degree(s):
MD, University of Rennes, France
MPH, Epidemiology, University of Hawaiʻi at Mānoa
PhD, Epidemiology/Biostatistics, University of Hawaiʻi at Mānoa
Preventive Medicine Residency, University of Hawaiʻi at Mānoa
French Medical License and Certification in Public Health

Honors

2015, 2016, 2017, Thomson Reuters lists of "Highly Cited Researchers"
2016, Medal for Excellence in Research, Regents of the University of Hawaiʻi

Research Focus

Dr. Le Marchand has conducted research on lifestyle and genetic risk factors for cancer of the lung, breast and colorectum with uninterrupted NCI funding since 1987. His particular focus of research is the role of biological and environmental factors in the etiology and progression of cancer, especially in regard to explaining ethnic/racial differences in cancer risk and survival. He has conducted several case-control and intervention studies in Hawaiʻi and is the founder of the Hawaiʻi Colorectal Cancer Family Registry. Since 2012, he has been the Contact PI of the Multiethnic Cohort (MEC) Study and the PI of a program project grant on obesity and cancer.

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 the 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 effects of the environment and genetics. These genetic factors and their interactions with environmental exposures remain largely unknown. Dr. Le Marchand’s group has identified 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. These anomalies provide unique opportunities to identify new risk factors and/or potentially important gene-environment interactions.

Colorectal Cancer (CRC). We showed that the Japanese who migrated to Hawaiʻi have a particular susceptibility to the effect of the western lifestyle on CRC risk, as their rates increased as early as in the first generation of migrants to surpass those of whites. The same phenomenon has taken place in Japan during the last few decades where CRC rates are now among the highest in the world. We have conducted a number of studies suggesting that exposure to chemical carcinogens, especially heterocyclic aromatic amines (HAA), through a high red meat diet and smoking, combined with a genetically-derived greater ability to bioactivate these carcinogens, may contribute to the extremely high Japanese rates for this disease. We have now expanded this research by conducting a GWAS of CRC in Japanese and African Americans, the two groups with the highest rates for this cancer in the U.S. We have identified several new risk variants for this cancer and confirmed the modifying effect of NAT2 on the red meat-CRC association. We have also developed long-term biomarkers of HAA exposure, working with Dr. Robert Turesky (University of Minnesota).

Obesity: Similarly, we showed in the MEC that body mass index (BMI) carries different risks for cancer across ethnic groups. The effect of BMI on breast cancer risk was stronger and observed at a lower level of body fatness in Japanese than the other ethnic groups. This observation led us to hypothesize that visceral fat carries a greater cancer risk than sub-cutaneous fat, as it does for certain risk factors (e.g., diabetes, early menarche). This and a similar observation for colorectal and liver cancers were the premise for our P01 (CA168530) in which 1,861 healthy MEC participants (median age: 69 years) were recruited back to undergo a whole-body DXA and abdominal MRI and anthropometric measurements. Visceral (VAT) and liver fat, adjusted for total adiposity, showed major differences by race and was highest among Japanese Americans, lowest among African Americans, and intermediate among Native Hawaiians, Latinos, and whites. These findings are highly significant since VAT and liver fat carry a higher metabolic risk than sub-cutaneous fat and peripheral fat. We have developed a set of blood biomarkers, which, when added to a model with age, sex, race and BMI, significantly improves the prediction of ectopic fat, with AUROC of 0.93-0.97 for visceral obesity (≥150 cm2) and 0.83-0.93 for non-alcoholic fatty liver disease (NAFLD; ≥5% liver fat) across ethnic groups. Applying the VAT prediction score by measuring these biomarkers in the pre-diagnostic samples in MEC, we were able to confirm the P01’s central hypothesis that the score was associated with risks of breast and colorectal cancers independently of BMI and other risk factors. We also developed a robust methodology to sample the fecal microbiome in large epidemiological studies and demonstrated that it is stable in individuals over multiple years. We described associations of specific genera and imputed microbial functions with total adiposity and liver fat, and with race/ethnicity. We also observed associations between diet quality indices, including the Mediterranean Diet Score, with lower levels of visceral and liver fat. These results are being further related to biochemical, hormonal, metabolomic, genomic and gut microbiome markers measured on these participants. A better understanding of the causes of the adiposity patterns that carry the highest metabolic and cancer risks, may open new avenues for prevention and treatment.

Lung Cancer: We also showed that there exist large ethnic/racial differences in the risk of lung cancer associated with smoking. We first made these observations in a case-control study, then, replicated and expanded them with our USC colleagues in the MEC. We followed up this observation in an R01 and showed that the lower lung cancer risk of Japanese for a given lifetime smoking exposure is due to their slower nicotine metabolism by the enzyme CYP2A6, leading them to draw less nicotine and, as the result, less carcinogens, from each cigarette. We confirmed and expanded these findings in a P01 (CA138338) with University of Minnesota colleagues through a GWAS of biomarkers assessing the metabolisms of nicotine and various tobacco carcinogens in smokers. In particular, we showed for the first time that the same GWAS hits associated with CYP2A6 activity were also associated with lung cancer risk.

Selected Publications

Maskarinec G, Lim U, Jacobs S, Monroe KR, Ernst T, Buchthal SD, Shepherd JA, Wilkens LR, Le Marchand L, Boushey CJ. (2017). Diet Quality in Midadulthood Predicts Visceral Adiposity and Liver Fatness in Older Ages: The Multiethnic Cohort Study. Obesity (Silver Spring). Aug;25(8):1442-1450. PMCID: PMC5604249.

Park SY, Boushey CJ, Wilkens LR, Haiman CA, Le Marchand L. (2017). High-quality Diets Associate With Reduced Risk of Colorectal Cancer: Analyses of Diet Quality Indexes in the Multiethnic Cohort. Gastroenterolog., Aug;153(2):386-394.e2. doi: 10.1053/j.gastro.2017.04.004. Epub 2017 Apr 17 PMCID: PMC5526717.

Patel YM, Park SL, Han Y, Wilkens LR, et al., Amos C, Le Marchand L. (2016). Novel Association of Genetic Markers Affecting CYP2A6 Activity and Lung Cancer Risk. Cancer Res. Oct 1;76(19):5768-5776. PMCID: PMC5050097.

Le Marchand L, Yonemori K, White KK, Franke AA, Wilkens LR, Turesky RJ. (2016). Dose validation of PhIP hair level as a biomarker of heterocyclic aromatic amines exposure: a feeding study. Carcinogenesis. 6;37:685-91. PMCID: PMC4936386.

Wang H, Burnett T, Kono S, Haiman CA, Iwasaki M, Wilkens LR, Loo W LW, Van Den Berg D, Kolonel LN, Hederson BE, Keku TO, Sandler RS, Signorello LB, Blot WJ, Newcomb PA, Pande M, Amos CI, West DW, Bézieau S, Berndt SI, Zanke BW, Hsu L, Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), Lindor NM, Haile RW, Hopper JL, Jenkins MA, Gallinger S, Casey G, Colong Cancer Family Registry (CFR), Stenzel SL, Schumacher FR, Peters U, Gruber SB, Colorectal Transdisciplinary Study (CORECT), Tsugane S, Stram DO, Le Marchand L. (2014). Trans-ethnic genome-wide association study of colorectal cancer identifies a new susceptibility locus in VTI1A. Nat Commun, Aug 8;5:4613. PMC4180879.

Publication list via PubMed

Active Grants

L. Le Marchand, C. Henderson, L. Wilkens, MPIs
U01 CA164973, National Cancer Institute
"Understanding Ethnic Differences in Cancer: The Multiethnic Cohort Study"
09/12/12 – 08/31/22

Le Marchand L, PI of subcontract; Hecht, PI
P01 CA138338, National Cancer Institute
“Mechanisms of Ethnic Differences in Lung Cancer due to Cigarette Smoking”
09/25/16 – 08/31/21

Le Marchand L, PI of subcontract; Peters, Casey, Gauderman, Le Marchand, MPIs
R01 CA201407, National Cancer Institute
“Using Functional Genomics to Inform Gene Environment Interactions for Colorectal Cancer”
09/23/16 – 8/31/21

Le Marchand, PI of subcontract; Amos, Brennan, Hung, MPIs
U01 CA203654, National Cancer Institute
“Integrative analysis of lung cancer etiology and risk”
6/1/17 – 5/31/21

L. Le Marchand, PI
P01 CA168530, National Cancer Institute
"Obesity, Body Fat Distribution and Cancer Risk in the Multiethnic Cohort"
09/12/12 – 05/31/19

Le Marchand, PI of subcontract; Epplein, PI
R01 CA190428, National Cancer Institute
“Helicobacter pylori protein-specific antibodies and colorectal cancer risk”
5/1/16 – 4/30/19