Associations of common variants in genes involved in metabolism and response to exogenous chemicals with risk of multiple myeloma.

BACKGROUND: We examined risk of multiple myeloma (MM) associated with variants in genes involved in metabolism and response to exogenous chemicals [cytochrome P450 enzymes (CYP1B1, CYP2C9), epoxide hydrolase (EPHX1), paraoxonase 1 (PON1), arylhydrocarbon hydroxylase receptor (AHR), and NAD(P)H:quinone oxidoreductase (NQO1)]. METHODS: This study included 279 MM cases and 782 controls in a pooled analysis of two population-based case-control studies. One common variant from each candidate gene was genotyped using DNA from blood or buccal cells. We estimated risk of MM associated with each genotype, controlling for race, gender, study site, and age, using odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Evaluations of the CYP1B1 V432L variant (rs1056836) suggested increased risk of MM among persons with the CG and GG genotypes compared to the CC genotype [OR (95% CI)=1.4 (1.0-2.0)]. Similar results were seen in analyses stratified by race and gender. We did not find any associations between MM and the CYP2C9, EPHX1, NQO1, or PON1 genes. CONCLUSIONS: CYP1B1 activates chemicals such as polycyclic aromatic hydrocarbons and dioxins to create oxidized, reactive intermediates, and higher gene activity has been shown for the G allele. We conducted the largest analysis to date on MM and these genetic variants and our results provide preliminary evidence that variation in CYP1B1 may influence susceptibility to MM.

Community-Based Participatory Research and Gene-Environment Interaction Methodologies Addressing Environmental Justice among Migrant and Seasonal Farmworker Women and Children in Texas: "From Mother to Child Project"

The "From Mother to Child Project" is a molecular epidemiological study that employs a community- based participatory research (CBPR) approach and gene-environment interaction research to address environmental justice in migrant and seasonal farmworker (MSF) women and children of Mexican origin home-based in Baytown and La Joya, Texas. This paper presents the background and rationale for the study and describes the study design and methodology. Preliminary data showed that MSF women and children in Texas have measurable levels of pesticides in their blood and urine, some of which were banned in the United States decades ago and are possible human carcinogens. Polymorphisms in genes involved in chemical detoxification and DNA repair have been associated with susceptibility to genetic damage and cancer development in populations exposed to environmental toxins. The "From Mother to Child Project" is testing three hypotheses: (1) MSF women and children who are occupationally exposed to pesticides are at higher risk for DNA damage than are non-exposed women and children. (2) Both, the extent of pesticide exposure and type of polymorphisms in chemical detoxification and DNA repair genes contribute to the extent of DNA damage observed in study participants. (3) The mutagenic potency levels measured in the organic compounds extracted from the urine and serum of study participants will correlate with the total concentrations of pesticides and with the measured DNA damage in study participants. The study will enroll 800 participants: 200 MSF mother-child pairs; 200 children (one per family) whose parents have never worked in agriculture, matched with the MSF children by ethnicity, age ± 2 years, gender, and city of residence; and these children's mothers. Personal interviews with the mothers are used to gather data for both mothers and children on sociodemographic characteristics; pesticide exposure at work and home; medical and reproductive history; dietary assessment, and lifestyle factors. Blood and urine samples are collected from each participant and analyzed for (1) organochlorine and organophosphate pesticide levels, (2) genetic polymorphisms of chemical detoxification and DNA repair genes, (3) DNA damage (chromosomal aberrations), and (4) the mutagenic potential of pesticides in the serum and urine. Recruitment and data collection in Baytown is near completion, and over one third of the target population for the La Joya study site.

Ethical issues in conducting migrant farmworker studies.

Migrant farmworkers should be considered a vulnerable population because they work in a hazardous industry, are often members of an ethnic minority, have known difficulty in accessing health care, and are often of lower socioeconomic status. For these reasons, too, it is extremely important to conduct health-related research with this often-underserved group. However, because migrant farmworkers are vulnerable, investigators must be especially vigilant in protecting them from the potential harms of research and in ensuring that the special ethical issues that arise in research with this population are identified and addressed for every project. In response to the National Cancer Institute's concerns about the feasibility of conducting epidemiologic studies among migrant farmworkers, researchers undertook four feasibility studies near the Texas-Mexico border. Each study raised different, complex ethical questions that challenged the investigators, but whose resolution turned out to be crucial to the success of the studies.