Blood Lead Concentration Correlates with All Cause , All Cancer and Lung Cancer Mortality in Adults : A Population Based Study

Lead is a known weak carcinogen of human (Steenland and Boffetta, 2000). A study used lead concentration data available in National Health and Nutrition Examination Survey (NHANES) II (1976-1980) study found a correlation between high concentrations available in NHANES II study with higher all cancer mortality, but there was no significant correlation between overall blood lead level and cancer mortality (Jemal et al., 2002). In a later study using NHANES III (1988-1994) data, contemporary blood lead level in NHANES III was found to be associated with higher all cause and all cancer mortality at low concentrations (Menke et al., 2006; Schober et al., 2006). Further studies found increased mortality related to cancer and hypertension related cardiac diseases. Since there was no dose response, blood lead level was often thought to be surrogate for other factors (Wong and Harris, 2000). Other studies found blood lead level correlated with kidney disease and hypertension (Cooper, 1988), lung stomach and liver, hypertension, chronic nephritis and heart disease and other conditions Abstract


Introduction
Lead is a known weak carcinogen of human (Steenland and Boffetta, 2000).A study used lead concentration data available in National Health and Nutrition Examination Survey (NHANES) II (1976II ( -1980) ) study found a correlation between high concentrations available in NHANES II study with higher all cancer mortality, but there was no significant correlation between overall blood lead level and cancer mortality (Jemal et al., 2002).In a later study using NHANES III (1988-1994) data, contemporary blood lead level in NHANES III was found to be associated with higher all cause and all cancer mortality at low concentrations (Menke et al., 2006;Schober et al., 2006).Further studies found increased mortality related to cancer and hypertension related cardiac diseases.Since there was no dose response, blood lead level was often thought to be surrogate for other factors (Wong and Harris, 2000).Other studies found blood lead level correlated with kidney disease and hypertension (Cooper, 1988), lung stomach and liver, hypertension, chronic nephritis and heart disease and other conditions

Blood Lead Concentration Correlates with All Cause, All Cancer and Lung Cancer Mortality in Adults: A Population Based Study
Min Rex Cheung (Cooper et al., 1985).However, many of these earlier studies did not have enough socio-demographic data to adjust for potential covariates.This study investigated if contemporary blood lead concentration was related to all cause, all cancer and lung cancer.This was a part of a more extensive study to screen the potential predictors of adult cancer mortality using that NHANES III data that were representative of U.S. population.The vital status of NHANES III participant was followed passively up to December 31, 2006.The data were contained in NHANES III linked mortality (Menke et al., 2010).This study used the extensive socio-demographic factors available in NHANES III data to adjust for the effects of blood lead level and all cause, all cancer and lung cancer mortality.

Materials and Methods
NHANES is a major program of National Center of Health Statistics (a part of Center of Disease Control (CDC) of United States of America) started in 1971.NHANES III was a national study based on a complex, multi-stage probability sampling design.For details of NHANES III and NHANES III linked mortality data and statistical guidance as well as their analysis examples see NHANES website (http://www.cdc.gov/nchs/nhanes.htm).In brief, NHANES studies were approved by CDC internal institutional review boards.The public use data were made available to the public and researchers.The NHANES sample weights were calculated to represent non-institutionalized general U.S. population to account for non-coverage and non-response.Only participants who were interviewed at home and examined in mobile examination centers (MEC) were included in this study.This eliminated the cofounding effects of sample persons being too frail, too young or old to go to the MEC for examinations.In this study, NHANES III (conducted with NHANES III laboratory data and the NHANES III linked cancer mortality data. Detailed information about the data and analysis guidelines are available at their website (http://www.cdc.gov/nchs/data_access/data_linkage/mortality/nhanes3_ linkage.htm).In brief, probability matching was used to link NHANES III with National Death Index for vital status and mortality.NHANES used multiple sources Death Index to ascertain vital status and cause of death.NHANES III codes of death (ucod_113) were used in this study.
NHANES III employed a complex sampling strategy and analysis (Ezzati-Rice and Murphy, 1995;Graubard and Korn, 1999;Lemeshow and Cook, 1999;Chang et al., 2010).Matlab programs (posted on Matlab File Exchange) were developed to convert SAS files provided by NAHNES to STATA programs to download NHANES III is needed for NHANES complex data analysis (Cohen, 1997).STATA 12 (College Station, TX) was among those recommended by CDC to analyze the complex NHANES data and was used in this study.The sampling weight used was WTPFEX6 because only the sample persons had examinations in the MEC were included in this study, SDPPSU6 was used for the probability sampling unit (PSU) and SDPSTRA6 was used to designate the strata for the STATA survey commands.STATA scripts were written for this analysis, and will be submitted for publication separately.Univariate and multivariate logistic regressions (Jewell, 2004) were used to study the relationship between predictors and mortality (using ucod_113 codes) in adults.The symbols used were as follows: lungCancer (death from lung cancer (ucod_113 = 027, malignant neoplasms of trachea, bronchus and lung)): 0=alive, 1=dead, BMI (body mass index), IndicatorDeath (death from all causes) and cancerDeath (death form all cancer causes).MXPAXTMR (age at the MEC using male as the reference group), PBP (blood lead level, ug/dL), DMPMETRO (urban rural residence status, _IDMPMETRO_2=rural residence, urban residence used as the reference group), DMARETHN (race and ethnicity, _IDMARETHN_2=non-Hispanic black, _IDMARETHN_3=Mexican-American, _ IDMARETHN_4=others, non-Hispanic white was used as the reference group), HAN6JS (alcohol consumption), and HAR4S (smoking), DMPPIR (poverty index ratio status).N=3482 samples with complete data were analyzed.Linearized Taylor Standard Error estimation was used.

Discussion
The relationship between blood lead and increased mortality due to heart, kidney and cancer cause is known but appears to be complex (Steenland and Boffetta, 2000).A major limitation of prior studies was a lack of data to adjust for the covariates of the effects of blood lead level on human illnesses.It has been observed that blood lead level correlated with increase mortality due to cancer, and hypertension related cardiac diseases (Wong and Harris, 2000).For cancer, studies have found an association between blood lead level and lung, stomach and liver cancer mortality (Cooper et al., 1985).Earlier studies suggested that lead level at 1975-1976 after control the lead content of gasoline might be enough to normalize the mortality (Malcolm and Barnett, 1982), but later studies found an increase in mortality at low concentrations (Menke et al., 2006;Schober et al., 2006).Lung cancer mortality was associated with blood lead level, but it was thought that lead concentration could be a surrogate for smoking (Wong and Harris, 2000).This study made use of the extensive socio-demographic NHANES III data to adjust for the covariates of the effects of blood lead level on all cause, all cancer, and lung cancer mortality.
All of the results were obtained by using specialized survey software taking into account the primary sampling to the sample persons examined in the MEC.Thus these results are representative of the US population.3482 sample participants with complete information for all variables were included in this analysis.All of analysis of all cause, all cancer and lung cancer mortality so as not to omit potentially important covariates.For all body mass index, age, blood lead concentration, poverty income ratio and drinking hard liquor.For all cancer blood lead concentration, black race, using non-Hispanic white as reference, and smoking.For lung cancer mortality blood lead concentration, Mexican Americans, using non-Hispanic white as reference, other races, and smoking.
Alcohol consumption, poverty, minority race and smoking have been associated with increased all cause and cancer mortality (Rothman et al., 2008).This study confirmed these earlier results.This study found an association of black race and increased all cancer mortality.correlated with lower lung cancer mortality needs to be further examined to see they are confounders of other hidden socio-economic covariates.This study found a correlation of blood lead level, as in the contemporary NHANES III data and blood lead concentrations, and increase in all cause, all cancer and lung cancer mortality after adjusting for other socio-economic covariates.However, the mechanism of how an increase in blood lead level increased all lung cancer mortality will need further studies.