Background: Previous analyses from the National Health and Nutrition Examination Survey (NHANES III) have found that elevated blood lead levels may be associated with cardiovascular mortality, cancer mortality, and all-cause mortality. The 5-aminolevulinic acid dehydratase (ALAD) G177C genetic polymorphism (rs 1800435) affects lead toxicokinetics and may alter the adverse effects of lead exposure. We examined whether the ALAD G177C single nucleotide polymorphism (SNP) affects the relationship between lead and mortality.
Methods: We analyzed a subset of 3349 genotyped NHANES III participants at least 40 years of age. Using Cox proportional hazards regression, we estimated the relative risk of all-cause, cardiovascular disease, and cancer mortality by ALAD genotype, and by blood lead levels (<5 μg/dL vs. ≥5 μg/dL). We also tested whether the ALAD genotype modified the relationship between blood lead level and mortality.
Results: The adjusted overall relative risk for participants with the variant ALADCG/CC genotype was decreased for all-cause mortality (hazards ratio = 0.68; [95% confidence interval = 0.50–0.93]) compared with persons having the common GG genotype. There was some suggestion that higher lead levels were associated with cancer mortality (1.48 [0.92–2.38]). We observed no convincing interaction effect between ALAD genotype and blood lead level on mortality risk.
Conclusion: The ALADCG/CC genotype may be associated with decreased mortality from all causes and from cancer. This association does not seem to be affected by lead exposure.
From the aCancer Prevention Fellowship Program, National Cancer Institute, Rockville, MD; bDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD; cDepartment of Mathematics, University of Texas at Arlington, Arlington, TX; dNorthrop Grumman/Division of Health and Nutrition Examination Surveys, National Center for Health Statistics, Centers for Disease Control and Prevention, Hyattsville, MD; and eNational Office of Public Health Genomics, Centers for Disease Control and Prevention, Atlanta, GA.
Submitted 5 February 2010; accepted 1 October 2010.
Supported by intramural funds from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services.
Correspondence: Dana M. van Bemmel, Cancer Prevention Fellowship Program, Center for Cancer Training, National Cancer Institute, 6120 Executive Blvd, Suite 150E, Rockville, MD 20852. E-mail: firstname.lastname@example.org.