The very interesting article by de Vocht et al (1) is a good
opportunity to discuss possible interpretations of results obtained in
ecological studies. The study included 165 nations as observations and
found an association between mobile/cellular telecommunications (per 100
people) and brain cancer (national age-adjusted incidence rates). Although
in this case authors were interested in the generation of individual-level...
The very interesting article by de Vocht et al (1) is a good
opportunity to discuss possible interpretations of results obtained in
ecological studies. The study included 165 nations as observations and
found an association between mobile/cellular telecommunications (per 100
people) and brain cancer (national age-adjusted incidence rates). Although
in this case authors were interested in the generation of individual-level
causal hypotheses, the same results can be interpreted in two more ways
based on multilevel causal approach,(2) promulgated by social
epidemiologists.
One first alternative interpretation can be called "full-population
approach". According to the classic article by Rose, determinants of
individual cases are not necessarily determinants of incidence rate.(3) In
this approach there is not interest in individual or other level
inferences, thus results of one ecological study could be valid in the
same aggregation level of observations analyzed. Until I know only one
study used national data from Nordic countries,(4) and its inconsistent
results can be explained per difficulties to explore latency periods. For
this, my conclusion is that de Vocht et al study is the most valid study
at national aggregation level.
The second alternative interpretation is interested in an ecological
approach but in different aggregation levels. For instance, it occurs when
ecological studies based on national data are evidence for national sub-
regions inferences. It can be possible but the presence of fallacy is a
threat. In this case is needed to explore cross-level fallacies similar to
ecological fallacy.(5) A discussion on this same topic is available in two
commentaries,(6,7) and inferences on different aggregation-levels can be
responsible of heterogeneity observed.
Explanations of these alternatives approaches should not to be based
on biomedical concepts. Macrodeterminants and population-level outcomes
act according to ecologic, social, cultural or economical processes. Thus
an initial explanation of results can be based on a previous study by
Milham, where "civilization" is the main determinant of some diseases with
high occurrence in recent years. (8)
In conclusion, I agree with the authors that in occupational and
environmental health ecological studies can be a useful source of
evidence. However their results can offer more evidence if they are
analyzed according to different aggregation-level approaches.
References
1. de Vocht F, Hannam K, Buchan I. Environmental risk factors for
cancers of the brain and nervous system: the use of ecological data to
generate hypotheses. Occup Environ Med 2013 (in press).
2. Diez-Roux AV. A glossary for multilevel analysis. J Epidemiol
Community Health 2002;56(8):588-94.
3. Rose G. Sick individuals and sick populations. Int J Epidemiol
1985;14(1):32-8.
4. Deltour I, Auvinen A, Feychting M, Johansen C, Klaeboe L, Sankila
R, Schuz J. Mobile phone use and incidence of glioma in the Nordic
countries 1979-2008: consistency check. Epidemiology 2012;23(2):301-7.
5. Idrovo AJ. Three criteria for ecological fallacy. Environ Health
Perspect 2011;119:A332.
6. Soderqvist F, Carlberg M, Hansson Mild K, Hardell L. Childhood
brain tumour risk and its association with wireless phones: a commentary.
Environ Health 2011;10:106.
7. Aydin D, Feychting M, Schuz J, Roosli M; CEFALO study team.
Childhood brain tumours and use of mobile phones: comparison of a case-
control study with incidence data. Environ Health 2012;11:35.
8. Milham S. Historical evidence that electrification caused the 20th
century epidemic of "diseases of civilization". Med Hypotheses
2010;74(2):337-45.
The authors want to thank Prof. Dr. Kawada for his interest in our
manuscript entitled 'Adverse effects of low occupational cadmium exposure
on renal and oxidative stress biomarkers in solderers' [1]. Prof. Kawada
recommends performing the multiple linear regression analysis without
adjusting for pack-years of smoking. It is known that smoking is a major
source of cadmium exposure [2, 3]. However, we want to underline th...
The authors want to thank Prof. Dr. Kawada for his interest in our
manuscript entitled 'Adverse effects of low occupational cadmium exposure
on renal and oxidative stress biomarkers in solderers' [1]. Prof. Kawada
recommends performing the multiple linear regression analysis without
adjusting for pack-years of smoking. It is known that smoking is a major
source of cadmium exposure [2, 3]. However, we want to underline that the
possibility of confounding through a non-cadmium-dependent effect of
smoking on the kidney must also be considered [2-6]. Therefore, we decided
also to adjust for pack-years of smoking. The renal markers NAG, micro-Alb
and RBP showed indeed negative regression coefficients. However, the
regression coefficients are very small and very imprecise. To comply with
space considerations, we did not show the regression coefficients and
standard errors for the intercept, age and pack-years of smoking in the
paper. Pack-years of smoking is statistically significantly associated
with the oxidative stress marker 8-isoprostane (model Cd-B: regression
coefficient, B = 0.05; 95% confidence interval, C.I. = 0.02 - 0.07; p
<0.001 and model Cd-U: B = 0.05; 95% C.I. = 0.02 - 0.07; p < 0.01).
The association between NAG and pack-years of smoking was borderline
statistically significant (model Cd-B: B = 0.03; 95% C.I. = -0.001 - 0.06;
p= 0.06 and model Cd-U: B = 0.03; 95% C.I. = -0.004 - 0.06; p = 0.08). No
statistically significant association was found between pack-years of
smoking and the other renal markers (i.e., IAP, micro-Alb and RBP) and
oxidative stress markers (i.e., d-ROM, GPX, SOD, 8-OHdG and AOPP).
References
1. Hambach R, Lison D, D'Haese P, Weyler J, Francois G, De Schryver
A, Manuel-Y-Keenoy B, Van Soom U, Caeyers T, van Sprundel M. Adverse
effects of low occupational cadmium exposure on renal and oxidative stress
biomarkers in solderers. Occup Environ Med 2013; 70: 108-13.
2. Jarup L, Berglund M, Elinder CG, Nordberg G, Vahter M. Health
effects of cadmium exposure - a review of the literature and a risk
estimate. Scand J Work Environ Health 1998; 24: 1-51.
3. Bernhard D, Rossmann A, Wick G. Metals in Cigarette Smoke. IUBMB
Life 2005; 57: 805-9.
4. McNamee R. Confounding and confounders. Occup Environ Med 2003;
60: 227-34.
5. Orth SR, Viedt C, Ritz E. Adverse effects of smoking in the renal
patient. Tohoku J Exp Med 2001; 194: 1-15.
6. Mercado C, Jaimes EA. Cigarette smoking as a risk factor for
atherosclerosis and renal disease: novel pathogenic insights. Curr
Hypertens Rep 2007; 9: 66-72.
The finding that nightshift work is linked to increased risk of
ovarian cancer1 is one of a long series of studies finding that nightshift
work is associated with increased risk of cancer [e.g., Ref. 2]. While
reduced production of melatonin is a possible explanation, a better
explanation is that since those on night shift sleep during daytime, they
spend less time in the sun when they could be making vitamin D. Solar
ul...
The finding that nightshift work is linked to increased risk of
ovarian cancer1 is one of a long series of studies finding that nightshift
work is associated with increased risk of cancer [e.g., Ref. 2]. While
reduced production of melatonin is a possible explanation, a better
explanation is that since those on night shift sleep during daytime, they
spend less time in the sun when they could be making vitamin D. Solar
ultraviolet-B (UVB) irradiance is the primary source of vitamin D for most
people.
Based on a study of night shift work and the risk of cancer in men,2
it was pointed out that a much better explanation than low melatonin was
low solar UVB and vitamin D [Grant, Am J Epi, in press]. Additional
support is found in the fact that night shift work is also associated with
reduced risk of skin cancer.3 Also, both solar UVB and vitamin D have been
found inversely correlated with risk of ovarian cancer.4,5
Thus, those working night shifts should consider taking vitamin D
supplements in amounts sufficient to raise serum 25-hydroxyvitamin D
concentrations to at least 75 nmol/l if not 100 nmol/l.4 To reach these
concentrations could take 1000 to 4000 IU/d vitamin D3.
References
1.Bhatti P, Cushing-Haugen KL, Kristine G, et al. Nightshift work and
risk of ovarian cancer. Occup Environ Med 2013 70:231-7.
2. Parent ME, El-Zein M, Rousseau MC, et al. Night work and the risk
of cancer among men. Am J Epidemiol. 2012;176:751-9.
3. Schernhammer ES, Razavi P, Li TY, et al. Rotating night shifts and
risk of skin cancer in the nurses' health study. J Natl Cancer Inst.
2011;103:602-6.
4. Grant WB. Update on evidence that support a role of solar
ultraviolet-B irradiance in reducing cancer risk. Anticancer Agents Med
Chem. 2013;13:140-6.
5. Toriola AT, Surcel HM, Calypse A, et al. Independent and joint
effects of serum 25-hydroxyvitamin D and calcium on ovarian cancer risk: A
prospective nested case-control study. Eur J Cancer. 2010;46:2799-805.
Conflict of Interest:
I receive funding from Bio-Tech Pharmacal (Fayetteville, AR), and the Sunlight Research Forum (Veldhoven) and have received funding from the UV Foundation (McLean, VA), the Vitamin D Council (San Luis Obispo, CA), and the Vitamin D Society (Canada).
Professor Kawada [1] commented on our use of Cox regression for the
analysis of cross-sectional data. [2] Although logistic regression is
often used to compute a prevalence odds ratio (POR) in cross-sectional
studies as an estimate of relative risk (RR), when the outcome is not rare
this overestimates the RR, sometimes changing the study conclusion. Cox
regression has been suggested instead to estima...
Professor Kawada [1] commented on our use of Cox regression for the
analysis of cross-sectional data. [2] Although logistic regression is
often used to compute a prevalence odds ratio (POR) in cross-sectional
studies as an estimate of relative risk (RR), when the outcome is not rare
this overestimates the RR, sometimes changing the study conclusion. Cox
regression has been suggested instead to estimate the prevalence rate
ratio (PRR).[3] We recently re-visited the relationship between POR and
PRR,[4] using the same dataset as the OEM article.[2] The logistic model
showed a POR of 1.22 (95%CI 1.10-1.35) in urban people (60.2%
hypertension) versus rural (55.3%), while a Cox model gave a PRR of 1.09
(1.02-1.16). The age-sex adjusted figures were 1.14 (1.03-1.27), and 1.06
(0.99-1.16) for the logistic and Cox models, respectively. In the case of
myocardial infarction (5.9% prevalence), however, we found similar RRs
between two models (age-sex adjusted POR 2.19, 1.75-2.74, and PRR 2.09,
1.68-2.59). [4] In our recent paper [2], the prevalence of severe
dementia syndromes was 10.6%, and if the a logistic model with the same
adjustments had been used, the POR would have been 1.43 (1.09-1.88). We
believe that the PRR of 1.29 (1.05-1.59) is more appropriate.
Professor Kawada made good comments on our data that smokers may
reduce the risk of severe dementia syndromes if avoiding exposure to
environmental tobacco smoke (ETS), although active smoking increased the
risk of dementia. The smokers must not smoke together (usually they do as
a culture), probably reducing both active and passive smoking in the
general population.
Since the situation of ETS in China remained little changed over the
last 3 decades, the ETS level to which the participants were exposed in
midlife may be similar to or even higher than that when they were older.
We will follow up the cohort to further examine the cause-effect
relationship between ETS and severe dementia syndromes.
Professor Ruoling Chen
Reference List
1 Kawada J. Environmental tobacco smoke and severe dementia
syndromes (comments). 2013.
2 Chen R, Wilson K, Chen Y, et al. Association between environmental
tobacco smoke exposure and dementia syndromes. Occup Environ Med 2013;70
(1):63-9.
3 Lee J. Odds ratio or relative risk for cross-sectional data? Int J
Epidemiol 1994;23 (1):201-3.
4 Wang J, Peng WJ, He Q, et al. Relationship between prevalence odds
ratio and prevalence rate ratio. Chinese J Health Statistics
2012;29:149-50.
Chen et al [1] reported the positive association between
environmental tobacco smoke (ETS) and severe dementia syndromes. They
mentioned that Cox regression model was applied to detect statistical
significance.
I have two queries on their study. First, they conducted cross-
sectional study and Cox regression analysis was applied to detect relative
risk by adjusting several confounders. They described the methodol...
Chen et al [1] reported the positive association between
environmental tobacco smoke (ETS) and severe dementia syndromes. They
mentioned that Cox regression model was applied to detect statistical
significance.
I have two queries on their study. First, they conducted cross-
sectional study and Cox regression analysis was applied to detect relative
risk by adjusting several confounders. They described the methodological
explanation in the 4th paragraph of the discussion, mainly avoiding
overestimation of the association. Although they quoted one reference [2]
with their previous two papers to select Cox regression analysis,
estimation of odds ratio by logistic regression analysis seems appropriate
in their cross-sectional study, because statistical advantage of handling
censored cases and duration from baseline to event occurrence was not
considered for their analysis.
Second, in their Table 1, 791 current smokers were categorized as no
ETS exposure group. There is no difference of ETS exposure from others or
from himself/herself, and ETS can be applied to never smokers or former
smokers in general. This also related to the content in Table 3, which
presents risk assessment of ETS to all participants, including current
smokers, with severe dementia syndromes. As Table 3 contains results for
3769 never smokers, their conclusion that highest ETS exposure by
cumulative dose is a significant risk factor for severe dementia syndromes
is acceptable.
The mean age is over 70 years in their study, and the validation of
ETS exposure for long-term period should also be evaluated. As there is a
report that heavy smoking in midlife becomes a risk of Alzheimer disease
[3], cause-effect relationship between ETS and severe dementia syndromes
by longer follow-up study with adjustment of several confounders should be
conducted to validate their results.
REFERENCES
1. Chen R, Wilson K, Chen Y, et al. Association between environmental
tobacco smoke exposure and dementia syndromes. Occup Environ Med
2013;70:63-9.
2. Zhang J, Yu KF. What's the relative risk? A method of correcting
the odds ratio in cohort studies of common outcomes. JAMA 1998;280:1690-1.
3. Rusanen M, Kivipelto M, Quesenberry CP Jr, et al. Heavy smoking in
midlife and long-term risk of Alzheimer disease and vascular dementia.
Arch Intern Med 2011;171:333-9.
Hambach et al [1] have published cross-sectional study on the
associations between cadmium (Cd) exposure and renal or oxidative stress
biomarkers in 36 solderers. They adopted multiple regression analysis to
detect statistical significance with adjustment of age and pack-years of
smoking. In contrast, there is a significant relationship between low
levels of Cd exposure and N-acetyl-beta-D-glucosaminidase (NAG) [2,3],
w...
Hambach et al [1] have published cross-sectional study on the
associations between cadmium (Cd) exposure and renal or oxidative stress
biomarkers in 36 solderers. They adopted multiple regression analysis to
detect statistical significance with adjustment of age and pack-years of
smoking. In contrast, there is a significant relationship between low
levels of Cd exposure and N-acetyl-beta-D-glucosaminidase (NAG) [2,3],
with special emphasis on smoking status [4,5].
I have two queries on their study. First, they used pack-years of
smoking as independent variables to know the effect of occupational Cd
exposure by excluding the effect of Cd exposure by smoking. In their
tables 3 and 4, explanation rate expressed by the square values of
multiple regression coefficient (R) were under 0.3, and significant levels
were near the borderline. I have some doubt on the validity of non-
occupational Cd exposure by pack-years of smoking, especially for
populations with low levels of Cd exposure. I want to recommend Hambach et
al to add the information on the relationship between Cd exposure and
renal or oxidative stress markers without adjustment by pack-years of
smoking. In addition, regression coefficients and standard errors of age
and pack-years of smoking should also be presented to know the effect of
age and smoking on several biomarkers.
Second, Hambach et al described in their Table 3 that urinary NAG was
normally distributed and logarithmic transformation was not conducted. In
addition, some of the gradients of three renal markers except IAP showed
negative values, which is difficult to explain biologically.
I suppose that the separation of occupational and non-occupational Cd
exposure is not easy in workers with low level of Cd exposure, and direct
relationship between Cd exposure and biological markers with only
adjustment of age would be informative to make comparison of their results
with past reports.
REFERENCES
1. Hambach R, Lison D, D'Haese P, et al. Adverse effects of low
occupational cadmium exposure on renal and oxidative stress biomarkers in
solderers. Occup Environ Med 2013;70:108-13.
2. Kawada T, Koyama H, Suzuki S. Cadmium, NAG activity, and beta 2-
microglobulin in the urine of cadmium pigment workers. Br J Ind Med
1989;46:52-5.
3. Noonan CW, Sarasua SM, Campagna D, et al. Effects of exposure to
low levels of environmental cadmium on renal biomarkers. Environ Health
Perspect 2002;110:151-5.
4. Akesson A, Lundh T, Vahter M, et al. Tubular and glomerular kidney
effects in Swedish women with low environmental cadmium exposure. Environ
Health Perspect 2005;113:1627-31.
5. Koyama H, Satoh H, Suzuki S, et al. Increased urinary cadmium
excretion and its relationship to urinary N-acetyl-beta-D-glucosaminidase
activity in smokers. Arch Toxicol 1992;66:598-601.
We read the article by Njoku and Orisakwe comparing blood lead levels
(BLL) in rural and urban pregnant women in Eastern Nigeria with great
interest [1]. The authors found that BLL were substantially higher in
rural areas than urban areas (135+/-160 vs 77+/-100 ug/dl). This in itself
is an important finding: it may reflect a stronger reliance on locally
grown foodstuffs in rural areas, combined with the effect of lead expo...
We read the article by Njoku and Orisakwe comparing blood lead levels
(BLL) in rural and urban pregnant women in Eastern Nigeria with great
interest [1]. The authors found that BLL were substantially higher in
rural areas than urban areas (135+/-160 vs 77+/-100 ug/dl). This in itself
is an important finding: it may reflect a stronger reliance on locally
grown foodstuffs in rural areas, combined with the effect of lead exposure
from soil and dust from farming. However, the authors understate the
importance of the overall BLL in this area of Eastern Nigeria (99+/-123
ug/dl). This level is substantially higher than has been found during
pregnancy in other developing countries (e.g. Mumbai, India (geometric
mean 6.4+/-1.69 ug/dl [2]) or in developed countries where there is a high
environmental exposure (e.g. Sweden (smelter) 2.63+/-0.31 ug/dl [3]), or
even in other countries in Africa (e.g. South Africa (median 2.3 ug/dl
[4]). The reported levels are sufficient to cause overt symptoms of lead
toxicity. As the authors note, there is free flow of lead though the
placenta, with the ratio of fetal:maternal lead being about 0.7-0.9. Thus,
the BLL of the newborn infants of these mothers will be about 80 ug/dl,
and will rise further with exposure from breast-milk and local foods, and
from the environment. These children are at extremely high risk of
neurological damage and impaired growth and development, as stated by the
authors. It is of note that the Centers for Disease Control and Prevention
(CDC) in the USA recommends chelation therapy for BLL of >45 ug/dl in
children [5]. The authors provide some data on the lead levels in local
staple foods: the high levels in these foods must reflect severe
contamination of farmland. The BLL in these pregnant women is of great
public health concern, not only for themselves, but also for their
children and subsequent generations.
References
1. Njoku CO, Orisakwe OE. Higher blood lead levels in rural than
urban pregnant women in Eastern Nigeria. Occ Environ Med 2012.doi
10.1136/oemed-2012-100947.
2. Raghunath R, Tripathi RM, Sastry VN, Krishnamurthy TM. Heavy
metals in maternal and cord blood. Sci Total Environ 2000;250:135-41.
3. Lagerkvist BJ, Ekesrydh S, Englyst V, Nordberg GF, Soderberg HA,
Wiklund DE. Increased blood lead and decreased calcium levels during
pregnancy: A prospective study of Swedish women living near a smelter. Am
J Pub Health 1996;86:1247-52.
4. Rudge CV, Rollin HB, Nogueira CM, Thomassen Y, Rudge MC, Odland
JO. The placenta as a barrier for toxic and essential elements in paired
maternal and cord blood samples of South African delivering women. J
Environ Monitor 2009;11:1322-30.
5. Centres for Disease Control. Lead. Managing elevated blood lead
levels among young children: recommendations from the Advisory Committee
on Childhood Lead Poisoning Prevention Committee 2002. Available at:
http://www.cdc.gov/nceh/lead/CaseManagement/caseManage_chap3.htm (accessed
20 September 2012).
The Editor
Occupational and Environmental Medicine
14th September, 2012
Cadmium, arsenic and lung cancer: A complete picture?
Were the occupational lung cancers among former employees at the
cadmium recovery plant located near Denver, CO, USA due to cadmium
exposures, arsenic exposures or both? One of us recently suggested that a
"simultaneous analysis of lung cancer risks in relation to both...
The Editor
Occupational and Environmental Medicine
14th September, 2012
Cadmium, arsenic and lung cancer: A complete picture?
Were the occupational lung cancers among former employees at the
cadmium recovery plant located near Denver, CO, USA due to cadmium
exposures, arsenic exposures or both? One of us recently suggested that a
"simultaneous analysis of lung cancer risks in relation to both recent and
distant cadmium and arsenic exposures" was required, and that researchers
should "let the data speak and not design an analysis that assumes in
advance which of these variables is important".[1] Although the new paper
from Robert Park and co-workers [2] does not appear to respond to these
suggestions, we believe their data could assist with authoritative
interpretation.
Findings from the only other cohort study to carry out an analysis of
occupational lung cancer risks in relation to quantitative estimates of
cadmium and arsenic exposures (and exposures to other metals) were
consistent with the hypotheses that recent arsenic exposures are more
important than distant exposures, and that cadmium exposures are
unimportant.[3] In addition indirect evidence that a late stage
carcinogen was operating at the Globe plant has already been provided.[4]
Analyses of recent exposures in the current study could be illuminating
and need to be carried out.
In addition, analyses in which the size of the arsenic effect is not
constrained need to be reported. Some of the later stages of processing
at the Globe plant would only have had exposures to cadmium because the
arsenic had already been removed (e.g. solution, pigment). This contrast
provides a cell with cadmium effects only. Therefore, there is the
potential for separating the independent effects of arsenic and cadmium,
without applying constraints to the modelling.
Reference
1. Sorahan T. Cadmium, arsenic and lung cancer: the bigger picture. Occup Med (Lond) 2010;60:236.
2. Park RM, Stayner LT, Petersen MR, et al. Cadmium and lung cancer mortality accounting for simultaneous arsenic exposure. Occup Environ Med 2012;69:303-9.
3. Jones SR, Atkin P, Holroyd C et al. Lung cancer mortality at a UK tin smelter. Occup Med (Lond) 2007;57:238-45.
4. Sorahan T. Lung cancer morality in arsenic-exposed workers from a cadmium recovery plant. Occup Med (Lond) 2009;59:264-6.
1Institute of Occupational and Environmental Medicine, University of
Birmingham, Edgbaston, Birmingham, B15 2TT, UK;
2Environmental and Occupational Health Sciences, University of Illinois at Chicago, School of Public Health (W) M/C 922, 2121 West Taylor St., Chicago, IL 60612, USA
We appreciate the interest of Dr. Garlantezec and colleagues in our
article on the association between maternal occupational exposure to
organic solvents (chlorinated, aromatic and Stoddard) and birth defects.
We reported a positive association between chlorinated solvents and neural
tube defects, particularly spina bifida; we did not observe an association
between solvent exposure and orofacial clefts.
We appreciate the interest of Dr. Garlantezec and colleagues in our
article on the association between maternal occupational exposure to
organic solvents (chlorinated, aromatic and Stoddard) and birth defects.
We reported a positive association between chlorinated solvents and neural
tube defects, particularly spina bifida; we did not observe an association
between solvent exposure and orofacial clefts.
As noted in their comment, our exposure assessment did not include
oxygenated solvents such as glycol ethers, which have been previously
linked with an increased prevalence of some birth defects, including both
oral clefts and neural tube defects. Garlantezec et al. suggest that our
exclusion of oxygenated solvents may explain our null findings for oral
clefts because women exposed to such solvents may be included in our
reference group, thereby introducing bias. Though potentially a plausible
explanation for our findings, we believe that bias due to the lack of
assessment for oxygenated solvents is unlikely. Based on preliminary,
unpublished data from an expert industrial hygienist review-based
assessment for the National Birth Defects Prevention Study, only 0.4
percent of working women in our study population had any exposure to
glycol ethers during pregnancy or the 3 months before conception. Because
the prevalence of occupational exposure to glycol ethers in our study
population is exceedingly rare, its omission would not result in a
meaningful underestimate of our effect measure estimates. However,
estimated exposure to other oxygenated solvents such as aliphatic
alcohols, ketones, esters and aldehydes in our study population is
unknown.
We agree with Dr. Garlantezec and colleagues that differences in the
definition of exposure (characterized by solvent type, formulation or
mixture, frequency and intensity, etc., as noted in our Discussion) may
explain apparent "inconsistencies" in reported results across studies. We
encourage further dialogue and research aimed at elucidating the true
underlying relation between exposure to distinct classes of organic
solvents and birth defects.
We read with interest the report by Desrosiers et al of the
association between maternal occupational exposure to organic solvents and
some birth defects [1]. Their case-control study examined occupational
exposure to three classes of solvents (chlorinated, aromatic and Stoddard)
and found one association -- between neural tube defects (mainly spinal
bifida) and maternal occupational exposure to chlorinated solvents, but n...
We read with interest the report by Desrosiers et al of the
association between maternal occupational exposure to organic solvents and
some birth defects [1]. Their case-control study examined occupational
exposure to three classes of solvents (chlorinated, aromatic and Stoddard)
and found one association -- between neural tube defects (mainly spinal
bifida) and maternal occupational exposure to chlorinated solvents, but no
association with the other solvent classes or with oral clefts. In their
discussion, the authors noted that previous findings of maternal
occupational exposure to solvents and oral clefts were from European,
mainly French, populations and hypothesized that the inconsistency between
their results and these previous studies might be due to different
exposure profiles (e.g., intensity, solvent formulation). Although this
explanation is plausible, another must be discussed: differences in the
definition of exposure. Our research team conducted four of the five
studies with positive results cited by Desrosiers et al[2][3][4][5]. All
four were population based and included, in addition to the solvent
classes considered by Desrosiers et al, oxygenated solvents, for example
alcohols or glycol ethers. Exposure limited to only oxygenated solvents
appears to be very frequent among working women: more than half of the
solvent exposure group in Chevrier et al [4] were exposed only to that
solvent class. Because previous studies found the increased risk of oral
clefts to be associated principally with that specific exposure, the
failure to consider this association could explain the negative findings
for oral clefts. Moreover, women who were exposed only to oxygenated
solvents are included in the reference ('non-exposed') group here, which
would result in underestimating associations with chlorinated and
petroleum solvents. For both these reasons, we think that the failure to
consider oxygenated solvents led to underestimating the risk estimates for
oral clefts.
1. Desrosiers, T.A., et al., Maternal occupational exposure to
organic solvents during early pregnancy and risks of neural tube defects
and orofacial clefts. Occup Environ Med 2012;69:7 493-499 Published Online
First: 23 March 2012 doi:10.1136/oemed-2011-100245.
2. Cordier, S., et al., Maternal occupational exposure and congenital
malformations. Scand J Work Environ Health, 1992. 18(1): p. 11-7.
3. Lorente, C., et al., Maternal occupational risk factors for oral
clefts. Occupational Exposure and Congenital Malformation Working Group.
Scand J Work Environ Health, 2000. 26(2): p. 137-45.
4. Chevrier, C., et al., Occupational exposure to organic solvent mixtures
during pregnancy and the risk of non-syndromic oral clefts. Occup Environ
Med, 2006. 63(9): p. 617-23.
5. Garlantezec, R., et al., Maternal occupational exposure to solvents and
congenital malformations: a prospective study in the general population.
Occup Environ Med, 2009. 66(7): p. 456-63.
The very interesting article by de Vocht et al (1) is a good opportunity to discuss possible interpretations of results obtained in ecological studies. The study included 165 nations as observations and found an association between mobile/cellular telecommunications (per 100 people) and brain cancer (national age-adjusted incidence rates). Although in this case authors were interested in the generation of individual-level...
The authors want to thank Prof. Dr. Kawada for his interest in our manuscript entitled 'Adverse effects of low occupational cadmium exposure on renal and oxidative stress biomarkers in solderers' [1]. Prof. Kawada recommends performing the multiple linear regression analysis without adjusting for pack-years of smoking. It is known that smoking is a major source of cadmium exposure [2, 3]. However, we want to underline th...
The finding that nightshift work is linked to increased risk of ovarian cancer1 is one of a long series of studies finding that nightshift work is associated with increased risk of cancer [e.g., Ref. 2]. While reduced production of melatonin is a possible explanation, a better explanation is that since those on night shift sleep during daytime, they spend less time in the sun when they could be making vitamin D. Solar ul...
In Reply,
Professor Kawada [1] commented on our use of Cox regression for the analysis of cross-sectional data. [2] Although logistic regression is often used to compute a prevalence odds ratio (POR) in cross-sectional studies as an estimate of relative risk (RR), when the outcome is not rare this overestimates the RR, sometimes changing the study conclusion. Cox regression has been suggested instead to estima...
Chen et al [1] reported the positive association between environmental tobacco smoke (ETS) and severe dementia syndromes. They mentioned that Cox regression model was applied to detect statistical significance.
I have two queries on their study. First, they conducted cross- sectional study and Cox regression analysis was applied to detect relative risk by adjusting several confounders. They described the methodol...
Hambach et al [1] have published cross-sectional study on the associations between cadmium (Cd) exposure and renal or oxidative stress biomarkers in 36 solderers. They adopted multiple regression analysis to detect statistical significance with adjustment of age and pack-years of smoking. In contrast, there is a significant relationship between low levels of Cd exposure and N-acetyl-beta-D-glucosaminidase (NAG) [2,3], w...
We read the article by Njoku and Orisakwe comparing blood lead levels (BLL) in rural and urban pregnant women in Eastern Nigeria with great interest [1]. The authors found that BLL were substantially higher in rural areas than urban areas (135+/-160 vs 77+/-100 ug/dl). This in itself is an important finding: it may reflect a stronger reliance on locally grown foodstuffs in rural areas, combined with the effect of lead expo...
The Editor Occupational and Environmental Medicine
14th September, 2012
Cadmium, arsenic and lung cancer: A complete picture?
Were the occupational lung cancers among former employees at the cadmium recovery plant located near Denver, CO, USA due to cadmium exposures, arsenic exposures or both? One of us recently suggested that a "simultaneous analysis of lung cancer risks in relation to both...
We appreciate the interest of Dr. Garlantezec and colleagues in our article on the association between maternal occupational exposure to organic solvents (chlorinated, aromatic and Stoddard) and birth defects. We reported a positive association between chlorinated solvents and neural tube defects, particularly spina bifida; we did not observe an association between solvent exposure and orofacial clefts.
As noted...
We read with interest the report by Desrosiers et al of the association between maternal occupational exposure to organic solvents and some birth defects [1]. Their case-control study examined occupational exposure to three classes of solvents (chlorinated, aromatic and Stoddard) and found one association -- between neural tube defects (mainly spinal bifida) and maternal occupational exposure to chlorinated solvents, but n...
Pages