A5075247272- Smoking Behavior and Cessation
- Biochemical Analysis and Sensing Techniques
- Nutritional Studies and Diet
- Air Quality and Health Impacts
- Genetic Associations and Epidemiology
- Air Quality Monitoring and Forecasting
- Vehicle emissions and performance
- Glutathione Transferases and Polymorphisms
- Epigenetics and DNA Methylation
- Genomics, phytochemicals, and oxidative stress
- BRCA gene mutations in cancer
- Genetic factors in colorectal cancer
- Nicotinic Acetylcholine Receptors Study
- Cardiovascular Health and Risk Factors
- Health, Environment, Cognitive Aging
- Carcinogens and Genotoxicity Assessment
- Sulfur Compounds in Biology
- Metabolomics and Mass Spectrometry Studies
- Multiple and Secondary Primary Cancers
- Alcohol Consumption and Health Effects
- DNA Repair Mechanisms
- Cancer Risks and Factors
- Synthesis and Biological Evaluation
- Nutrition, Genetics, and Disease
- Phytoestrogen effects and research
University of Hawaii Cancer Center
2011-2024
University of Hawaiʻi at Mānoa
2011-2024
University of Hawaii System
2011-2024
Cancer Center of Hawaii
2011-2024
University of Southern California
2014-2020
University of California, Los Angeles
2010
Background Assessing the relationship between lung cancer and metabolic conditions is challenging because of confounding effect tobacco. Mendelian randomization (MR), or use genetic instrumental variables to assess causality, may help identify drivers cancer. Methods findings We identified instruments for potential risk factors evaluated these in relation using 29,266 cases (including 11,273 adenocarcinomas, 7,426 squamous cell 2,664 small cases) 56,450 controls. The MR analysis suggested a...
Using a phenome-wide association study (PheWAS) approach, we comprehensively tested genetic variants for with phenotypes available 70,061 participants in the Population Architecture using Genomics and Epidemiology (PAGE) network. Our aim was to better characterize architecture of complex traits identify novel pleiotropic relationships. This PheWAS drew on five population-based studies representing four major racial/ethnic groups (European Americans (EA), African (AA),...
The Multiethnic Cohort epidemiology study has clearly demonstrated that, compared to Whites and for the same number of cigarettes smoked, African Americans Native Hawaiians have a higher risk lung cancer whereas Latinos Japanese lower risk. Acrolein crotonaldehyde are two important constituents cigarette smoke which well documented toxic effects could play role in etiology. Their urinary metabolites 3-hydroxypropylmercapturic acid (3-HPMA) 3-hydroxy-1-methylpropylmercapturic (HMPMA),...
Genetic variation in cytochrome P450 2A6 ( CYP2A6 ) gene is the primary contributor to intraindividual and interindividual differences nicotine metabolism has been found influence smoking intensity. However, no study evaluated relationship between genetic variants activity ratio (total 3-hydroxycotinine/cotinine) their on intensity [total equivalents (TNE)], across five racial/ethnic groups have disparate rates of lung cancer. This genotyped 10 known functional or copy number 2115 current...
Results of the Multiethnic Cohort (MEC) study demonstrated that, for same quantity cigarettes smoked, African Americans and Native Hawaiians have a higher risk lung cancer compared with whites, whereas Latinos Japanese lower risk. We hypothesize that uptake and/or metabolism carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) could explain differences in
While smoking is the primary cause of lung cancer, only 11-24% smokers develop malignancy over their lifetime. The addictive agent in tobacco smoke nicotine and variation metabolism may influence levels an individual. Therefore, inter-individual cancer risk among be due part to differences activity enzymes involved metabolism. In most smokers, cytochrome P450 2A6 (CYP2A6)-catalyzed C-oxidation accounts for >75% metabolism, this enzyme has been shown correlate with amount carcinogens drawn...
Lung cancer is the leading cause of cancer-related death. While cigarette smoking primary this malignancy, risk differs across racial/ethnic groups. For same number cigarettes smoked, Native Hawaiians compared to whites are at greater and Japanese Americans lower developing lung cancer. DNA methylation specific CpG sites (e.g., in AHRR F2RL3) most common blood epigenetic modification associated with status. However, influence internal dose, measured by urinary nicotine equivalents (NE), on...
Constituents of tobacco smoke can cause DNA double-strand breaks (DSBs), leading to tumorigenesis. The NBS1 gene product is a vital component in DSB detection and repair, thus genetic variations may influence cancer development. We examined the associations between polymorphisms haplotypes newly incident smoking-related cancers three case–control studies (Los Angeles: 611 lung 601 upper aero-digestive tract (UADT) cases 1040 controls; Memorial Sloan-Kettering Cancer Center: 227 bladder 211...
Abstract Body mass index (BMI) is inversely associated with lung cancer risk in observational studies, even though it increases the of several other cancers, which could indicate confounding by tobacco smoking or reverse causality. We used two-sample Mendelian randomization (MR) approach to circumvent these limitations epidemiology constructing a genetic instrument for BMI, based on results from GIANT consortium, was evaluated relation using GWAS 16,572 cases and 21,480 controls. Results...
Results from the Multiethnic Cohort Study demonstrated significant differences in lung cancer risk among cigarette smokers five different ethnic/racial groups. For same number of cigarettes smoked, and particularly light smokers, African Americans Native Hawaiians had highest for cancer, Whites intermediate risk, while Latinos Japanese lowest risk. We analyzed urine samples 331–709 participants each ethnic group this study metabolites phenanthrene, a surrogate carcinogenic polycyclic...
Abstract Background: 1,3-Butadiene (BD) is an important carcinogen in tobacco smoke that undergoes metabolic activation to DNA-reactive epoxides. These species can be detoxified via glutathione conjugation and excreted urine as the corresponding N-acetylcysteine conjugates. We hypothesize single nucleotide polymorphisms (SNPs) BD-metabolizing genes may change balance of BD bioactivation detoxification White, Japanese American, African American smokers, potentially contributing ethnic...
Abstract Women who have had breast cancer in the past are at increased risk of developing a second primary (SPC), including (SPBC) or non-breast (SPNBC). In Multiethnic Cohort (MEC) Study, we conducted prospective cohort analysis 3,223 female survivors from five racial/ethnic populations (White, African American, Japanese Latino, and Native Hawaiian) to assess association rare pathogenic variants (PV) 37 known predisposition genes with SPC. A total 719 (22.3%) women developed SPC, which, 323...
Smoking intensity varies across smokers and is influenced by individual variability in the metabolism of nicotine, major addictive agent tobacco. Therefore, lung cancer risk, which racial ethnic group, primary catalyst nicotine metabolism, cytochrome P450 2A6 (CYP2A6). In smokers, CYP2A6 catalyzes 5′-oxidation. vitro, also catalyzes, to a much lower extent, 2′-oxidation, leads formation 4-hydroxy-4-(3-pyridyl) butanoic acid (hydroxy acid). The urinary concentration hydroxy has been...
The Multiethnic Cohort Study has demonstrated that the risk for lung cancer in cigarette smokers among three ethnic groups is highest Native Hawaiians, intermediate Whites, and lowest Japanese Americans. We hypothesized differences levels of DNA adducts oral cells would be related to these differing risks cancer. Therefore, we used liquid chromatography-nanoelectrospray ionization-high resolution tandem mass spectrometry quantify acrolein-DNA adduct...
Systemic low-grade inflammation is a feature of chronic disease. C-reactive protein (CRP) common biomarker and used as an indicator disease risk; however, the role in not completely understood. Methylation epigenetic modification DNA which plays pivotal gene expression. In this study we evaluated differential methylation patterns associated with blood CRP level to elucidate biological pathways genetic regulatory mechanisms improve understanding inflammation. The racially ethnically diverse...
After accounting for smoking history, lung cancer incidence is greater in African Americans than Whites. In the multiethnic cohort, total nicotine equivalents (TNE) are higher Whites at similar reported cigarettes per day. Greater toxicant uptake cigarette may contribute to risk of Americans.
Abstract Background: While cigarette smoking is the leading cause of lung cancer, majority smokers do not develop disease over their lifetime. The inter-individual differences in risk among may part be due to variations exposure smoking-related toxicants. Methods: Using data from a subcohort 2,309 current at time urine collection Multiethnic Cohort Study, we prospectively evaluated association ten urinary biomarkers toxicants [total nicotine equivalents (TNE), ratio total...
We performed a hypothesis-generating phenome-wide association study (PheWAS) to identify and characterize cross-phenotype associations, where one SNP is associated with two or more phenotypes, between thousands of genetic variants assayed on the Metabochip hundreds phenotypes in 5,897 African Americans as part Population Architecture using Genomics Epidemiology (PAGE) I study. The PAGE was National Human Genome Research Institute-funded collaboration four sites accessing diverse...
Differences in internal dose of nicotine and tobacco-derived carcinogens among ethnic/racial groups have been observed. In this study, we explicitly examined the relationships between genetic ancestries (genome-wide average) 19 biomarkers smokers from 3 admixed Multiethnic Cohort Study (1993–present), namely, African ancestry Americans (n = 362), Amerindian Latinos 437), Asian Native Hawaiian Hawaiians 300). After multiple comparison adjustment, both were significantly related to a greater...
Approximately 10% of smokers will develop lung cancer. Sensitive predictive biomarkers are needed to identify susceptible individuals. 1,3-Butadiene (BD) is among the most abundant tobacco smoke carcinogens. BD metabolically activated 3,4-epoxy-1-butene (EB), which detoxified via glutathione conjugation/mercapturic acid pathway form monohydroxybutenyl mercapturic (MHBMA) and dihydroxybutyl (DHBMA). Alternatively, EB can react with guanine nucleobases DNA N7-(1-hydroxyl-3-buten-1-yl) (EB-GII)...
Abstract Background: Ultrafine particles (UFP) are unregulated air pollutants abundant in aviation exhaust. Emerging evidence suggests that UFPs may impact lung health due to their high surface area-to-mass ratio and deep penetration into airways. This study aimed assess long-term exposure airport-related cancer incidence a multiethnic population Los Angeles County. Methods: Within the California Multiethnic Cohort, we examined association between incidence. Multivariable Cox proportional...
Abstract Introduction The nicotine metabolite ratio and equivalents are measures of metabolism rate intake. Genome-wide prediction these biomarkers in multiethnic samples will enable tobacco-related biomarker, behavioral, exposure research studies without measured biomarkers. Aims Methods We screened genetic variants genome-wide using marginal scans applied statistical learning algorithms on top-ranked variants, age, ethnicity sex, and, additional modeling, cigarettes per day (CPD), (in...
At similar smoking levels, African American's lung cancer risk is as much twice that of whites. We hypothesized racial/ethnic differences in UDP-glucuronosyltransferase (UGT)-catalyzed glucuronidation 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), a detoxication pathway for the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) may contribute to this variable risk. UGT2B10 catalyzes NNAL-N-glucuronidation, and splice variant common among Americans....