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Blood lead levels, ALAD gene polymorphisms, and mortality
Dana M van Bemmel1, Yan Li, Jody McLean
1Cancer Prevention Fellowship Program, National Cancer Institute, Rockville, MD 20852, USA. vanbemmeld@mail.nih.gov
Epidemiology (Cambridge, Mass.)
|February 5, 2011
Summary
The 5-aminolevulinic acid dehydratase (ALAD) genotype may reduce all-cause and cancer mortality risk, independent of blood lead levels. This genetic factor appears to influence overall mortality, not just lead-related outcomes.
Area of Science:
- Environmental Health
- Genetics
- Epidemiology
Background:
- Previous research links elevated blood lead levels to increased mortality from cardiovascular disease, cancer, and all causes.
- The 5-aminolevulinic acid dehydratase (ALAD) G177C genetic polymorphism influences how the body processes lead.
- This study investigates if the ALAD genotype modifies lead's impact on mortality risk.
Purpose of the Study:
- To determine if the ALAD G177C polymorphism affects the association between blood lead levels and mortality.
- To evaluate the independent effects of ALAD genotype on all-cause, cardiovascular disease, and cancer mortality.
Main Methods:
- Analysis of 3349 genotyped participants from the National Health and Nutrition Examination Survey (NHANES III) aged 40 and older.
- Cox proportional hazards regression used to estimate mortality risk based on ALAD genotype and blood lead levels (<5 microg/dL vs. ≥5 microg/dL).
- Tested for interactions between ALAD genotype and blood lead level in relation to mortality risk.
Main Results:
- The variant ALAD genotype was associated with a reduced relative risk of all-cause mortality (HR=0.68) compared to the common GG genotype.
- A potential association between higher blood lead levels and increased cancer mortality was suggested (HR=1.48).
- No significant interaction was found between ALAD genotype and blood lead level concerning mortality risk.
Conclusions:
- The ALAD genotype may be independently associated with lower all-cause and cancer mortality.
- Lead exposure does not appear to significantly alter the observed association between ALAD genotype and mortality risk.
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