thyroid cancer is a common endocrine malignancy that has rapidly increased in global incidence in recent decades . in the united states ,
the 6.6% average annual increase in thyroid cancer incidence between 2000 and 2009 is the highest among all cancers .
although the death rate of thyroid cancer is relatively low , the rate of disease recurrence or persistence is high , which is associated with increased incurability , morbidity , and mortality   the prevalence of obesity has dramatically increased in the last 2 decades .
the diagnosis of obesity is often based on body mass index ( bmi ) , calculated as weight in kilograms divided by height in meters squared ( kg / m ) .
obesity has long been recognized as a trigger for many diseases , such as hypertension , hypercholesterolemia , diabetes , and insulin resistance .
additionally , during the last decades obesity has been consistently related to the development and progression of different types of cancers .
an extensive review published a few years ago estimated that 20% of all cancers might be caused by obesity .
the relationship between obesity and risk of thyroid cancer has been studied for more than 10 years .
several studies found obesity to be a risk factor in thyroid cancer , but other studies showed no association between obesity and risk of thyroid cancer .
two meta - analyses investigated the association between obesity and thyroid cancer risk , reporting that obesity was associated with thyroid cancer risk .
therefore , in this study we conducted a meta - analysis to assess the association between obesity and thyroid cancer risk .
we searched pubmed , embase , springer link , ovid , chinese wanfang data knowledge service platform , chinese national knowledge infrastructure ( cnki ) , and chinese biology medicine ( cbm ) databases up to 10 august 2014 .
 body mass index. we included articles if they met all the following criteria : ( 1 ) evaluation of obesity and thyroid cancer risk , ( 2 ) using a case - control or cohort design , ( 3 ) adjusted risk ratios ( rrs ) , hazard ratios ( hrs ) , or odds ratios ( ors ) with 95% confidence intervals ( cis ) were reported .
if they encountered conflicting evaluations , agreement was reached following a discussion ; if they could not reached agreement , another author was consulted to resolve the debate .
the following information was extracted from each study : first author , year of publication , study type , ethnicity , age , sex , years of follow - up , sample size , number of cases , covariates , adjusted or / hr / or , and the corresponding 95% ci of thyroid cancer risk . for thyroid cancer risk , we calculated summary rrs and 95% cis for obesity versus normal weight .
statistical heterogeneity among studies was evaluated using the q and i statistics . for the i
metric , we considered low , moderate , and high i values to be 25% , 50% , and 75% , respectively .
we did subgroup analyses according to study type , sex , race , pneumonia type , age , smoking status , and histology .
sensitivity analysis was conducted by excluding 1 study at a time to explore whether the results were driven by 1 large study or by a study with an extreme result .
all statistical analyses were performed with stata software ( version 12.0 , stata corporation , college station , tx , usa ) .
a threshold of p<0.1 was used to decide whether heterogeneity was present . in other cases ,
we searched pubmed , embase , springer link , ovid , chinese wanfang data knowledge service platform , chinese national knowledge infrastructure ( cnki ) , and chinese biology medicine ( cbm ) databases up to 10 august 2014 .
we included articles if they met all the following criteria : ( 1 ) evaluation of obesity and thyroid cancer risk , ( 2 ) using a case - control or cohort design , ( 3 ) adjusted risk ratios ( rrs ) , hazard ratios ( hrs ) , or odds ratios ( ors ) with 95% confidence intervals ( cis ) were reported .
if they encountered conflicting evaluations , agreement was reached following a discussion ; if they could not reached agreement , another author was consulted to resolve the debate .
the following information was extracted from each study : first author , year of publication , study type , ethnicity , age , sex , years of follow - up , sample size , number of cases , covariates , adjusted or / hr / or , and the corresponding 95% ci of thyroid cancer risk .
for thyroid cancer risk , we calculated summary rrs and 95% cis for obesity versus normal weight .
for the i metric , we considered low , moderate , and high i values to be 25% , 50% , and 75% , respectively .
we did subgroup analyses according to study type , sex , race , pneumonia type , age , smoking status , and histology .
sensitivity analysis was conducted by excluding 1 study at a time to explore whether the results were driven by 1 large study or by a study with an extreme result .
all statistical analyses were performed with stata software ( version 12.0 , stata corporation , college station , tx , usa ) .
a threshold of p<0.1 was used to decide whether heterogeneity was present . in other cases ,
after detailed evaluations , 21 studies were selected for final meta - analysis [ 626 ] . a manual search of reference lists from these studies did not yield any new eligible study .
eleven studies reported 2 cohorts , and finally 32 studies ( n=12 620 676 ) were included in this meta - analysis .
the evaluations of the association between obesity and thyroid cancer risk are summarized in table 2 .
obesity was associated with a significantly increased risk of thyroid cancer when compared with normal weight ( adjusted rr=1.33 ; 95% ci , 1.241.42 ; i=25% ; figure 2 ) . in the subgroup analysis by study type , increased risk of thyroid cancer was found in cohort studies ( rr=1.29 ; 95% ci , 1.201.37 ; i=21% ) and case - control studies ( or=1.76 ; 95% ci , 1.362.28 ; i=0% ) , respectively . in the subgroup analysis according to sex , both obese men ( rr=1.26 ; 95% ci , 1.131.40 ; i=9% ) and women ( rr=1.43 ; 95% ci , 1.251.64 ; i=33% ) were significantly at risk of thyroid cancer .
when stratified by ethnicity , significantly elevated risk was observed in caucasians ( rr=1.26 ; 95% ci , 1.181.33 ; i=9% ) and in asians ( rr=1.54 ; 95% ci , 1.271.86 ; i=16% ) . in the age subgroup analysis , both young ( rr=1.23 ; 95% ci , 1.131.34 ; i=0% ) and old populations ( rr=1.28 ; 95% ci , 1.111.46 ; i=32% ) showed increased thyroid cancer risk .
subgroup analysis on smoking status showed that increased thyroid cancer risks were found in smokers ( rr=1.10 ; 95% ci , 1.021.20 ; i=0% ) and in non - smokers ( rr=1.20 ; 95% ci , 1.111.28 ; i=0% ) . in the histology subgroup analyses ,
increased risks of papillary thyroid cancer ( rr=1.26 ; 95% ci , 1.151.39 ; i=35% ) , follicular thyroid cancer ( rr=1.29 ; 95% ci , 1.081.53 ; i=33% ) , and anaplastic thyroid cancer ( rr=1.93 ; 95% ci , 1.233.03 ; i=0% ) were observed .
however , obesity was associated with decreased risk of medullary thyroid cancer ( rr=0.50 ; 95% ci , 0.270.97 ; i=1% ) . as shown in figure 3 ,
the results showed that the pooled ors tended to be stable . a single study involved in the meta - analysis
was deleted each time to reflect the influence of the individual data set on the pooled ors , and the corresponding pooled ors were not materially altered ( figure 4 ) .
after detailed evaluations , 21 studies were selected for final meta - analysis [ 626 ] . a manual search of reference lists from these studies did not yield any new eligible study .
eleven studies reported 2 cohorts , and finally 32 studies ( n=12 620 676 ) were included in this meta - analysis .
the evaluations of the association between obesity and thyroid cancer risk are summarized in table 2 .
obesity was associated with a significantly increased risk of thyroid cancer when compared with normal weight ( adjusted rr=1.33 ; 95% ci , 1.241.42 ; i=25% ; figure 2 ) . in the subgroup analysis by study type , increased risk of thyroid cancer was found in cohort studies ( rr=1.29 ; 95% ci , 1.201.37 ; i=21% ) and case - control studies ( or=1.76 ; 95% ci , 1.362.28 ; i=0% ) , respectively . in the subgroup analysis according to sex , both obese men ( rr=1.26 ; 95% ci , 1.131.40 ; i=9% ) and women ( rr=1.43 ; 95% ci , 1.251.64 ; i=33% ) were significantly at risk of thyroid cancer .
when stratified by ethnicity , significantly elevated risk was observed in caucasians ( rr=1.26 ; 95% ci , 1.181.33 ; i=9% ) and in asians ( rr=1.54 ; 95% ci , 1.271.86 ; i=16% ) . in the age subgroup analysis ,
both young ( rr=1.23 ; 95% ci , 1.131.34 ; i=0% ) and old populations ( rr=1.28 ; 95% ci , 1.111.46 ; i=32% ) showed increased thyroid cancer risk .
subgroup analysis on smoking status showed that increased thyroid cancer risks were found in smokers ( rr=1.10 ; 95% ci , 1.021.20 ; i=0% ) and in non - smokers ( rr=1.20 ; 95% ci , 1.111.28 ; i=0% ) . in the histology subgroup analyses ,
increased risks of papillary thyroid cancer ( rr=1.26 ; 95% ci , 1.151.39 ; i=35% ) , follicular thyroid cancer ( rr=1.29 ; 95% ci , 1.081.53 ; i=33% ) , and anaplastic thyroid cancer ( rr=1.93 ; 95% ci , 1.233.03 ; i=0% ) were observed .
however , obesity was associated with decreased risk of medullary thyroid cancer ( rr=0.50 ; 95% ci , 0.270.97 ; i=1% ) . as shown in figure 3 ,
the results showed that the pooled ors tended to be stable . a single study involved in the meta - analysis
was deleted each time to reflect the influence of the individual data set on the pooled ors , and the corresponding pooled ors were not materially altered ( figure 4 ) .
the present meta - analysis , including 12 620 676 subjects from 32 observational studies , explored the association between obesity and thyroid cancer risk .
this result remained significant in various types of studies , such as cohort studies and case - control studies .
in addition , obesity was significantly associated with thyroid cancer risk in males and females .
subgroup analyses stratified by ethnicity showed that obese asians had higher thyroid cancer risk than caucasians , but it is possible that random error may account for this difference .
in fact , only 6 studies investigated the association between obesity and thyroid cancer risk in asians .
.   found that dynamic patterns of change for thyroid hormones were not different in asian and western caucasian women . in the subgroup analysis by age , we found obesity exhibited increased thyroid cancer risk in young and old subjects . actually , when we limited the meta - analysis to studies that controlled for age , a significant association between obesity and thyroid cancer risk remained ( rr=1.30 ; 95% ci , 1.221.40 ; i=22% ) .
cigarette smoking is a pro - inflammatory stimulus and an important risk factor for cancer .
our results showed that both smokers and non - smokers had increased thyroid cancer risk .
obese subjects showed increased risks of papillary thyroid cancer , follicular thyroid cancer , and anaplastic thyroid cancer .
this result indicates that obesity may have a different effect on the pathogenesis and occurrence of thyroid cancer in different histologies .
however , why obesity could influence the different histological types of thyroid cancer is still uncertain .
clearly , more studies are needed to elucidate the differential effect of obesity in the various thyroid cancer types .
there were several potential explanations for why obese individuals may have higher risk of thyroid cancer .
first , there is a clinical association between higher serum thyroid - stimulating hormone ( tsh ) levels and increased risk of malignancy in human thyroid nodules and advanced stage of the disease .
some cross - sectional studies in euthyroid subjects demonstrated a positive association between serum tsh and bmi .
second , leptin levels were higher in thyroid cancer patients compared to healthy subjects in a case - control study .
third , insulin resistance , a common metabolic perturbation in obesity , may play a role in thyroid tumor growth , with insulin directly binding to insulin receptors or stimulating insulin - like growth factor , estrogen , or other hormones , such as tsh , to enhance the proliferation of thyroid cancer cells .
studies on the positive association between obesity and thyroid cancer will have important implications in the future , because obesity is a modifiable risk factor [ 4145 ] .
future studies on the effects of weight gain or weight loss on altering risk for thyroid cancer are essential .
first , it was the first study of interactions between age , histology , and smoking status specificities and obesity .
second , the methodological issues for meta - analyses , such as one - way sensitivity analysis and cumulative meta - analysis , were well investigated .
third , this meta - analysis included 32 studies ( n=12 620 676 ) and thus was more conclusive and more powerful than previous studies . results from one - way sensitivity analysis and cumulative meta - analysis suggest the high stability and reliability of our results .
heterogeneity and publication bias can be important influences on the results of meta - analyses . in our study
additionally , funnel plots and egger s tests were used to find potential publication bias .
thus , our results should be interpreted with caution and more studies are needed to confirm the effect of obesity on thyroid cancer risk .
first , the number of published studies was not sufficient for a comprehensive analysis , particularly for africans .
second , all the studies included in this meta - analysis used a case - control or cohort design , which are susceptible to recall and selection biases .
third , because this meta - analysis investigated only obesity , we can not exclude the possibility that the observed associations may be confounded by other lifestyle factors , such as lower physical activity or dietary factors .
this meta - analysis found a significant association between obesity and thyroid cancer risk , except medullary thyroid cancer .
further studies in more ethnic groups , especially african , are warranted to validate this result .
 backgroundseveral studies have evaluated the association between obesity and thyroid cancer risk . 
 however , the results remain uncertain . in this study 
 , we conducted a meta - analysis to assess the association between obesity and thyroid cancer risk.material/methodspublished literature from pubmed , embase , springer link , ovid , chinese wanfang data knowledge service platform , chinese national knowledge infrastructure ( cnki ) , and chinese biology medicine ( cbm ) were retrieved before 10 august 2014 . 
 we included all studies that reported adjusted risk ratios ( rrs ) , hazard ratios ( hrs ) or odds ratios ( ors ) , and 95% confidence intervals ( cis ) of thyroid cancer risk.resultsthirty-two studies ( n=12 620 676 ) were included in this meta - analysis . 
 obesity was associated with a significantly increased risk of thyroid cancer ( adjusted rr=1.33 ; 95% ci , 1.241.42 ; i2=25% ) . in the subgroup analysis by study type , increased risk of thyroid cancer was found in cohort studies and case - control studies . in subgroup analysis by sex , 
 both obese men and women were at significantly greater risk of thyroid cancer than non - obese subjects . 
 when stratified by ethnicity , significantly elevated risk was observed in caucasians and in asians . in the age subgroup analysis , 
 both young and old populations showed increased thyroid cancer risk . 
 subgroup analysis on smoking status showed that increased thyroid cancer risks were found in smokers and in non - smokers . in the histology subgroup analyses , 
 increased risks of papillary thyroid cancer , follicular thyroid cancer , and anaplastic thyroid cancer were observed . 
 however , obesity was associated with decreased risk of medullary thyroid cancer.conclusionsour results indicate that obesity is associated with an increased thyroid cancer risk , except medullary thyroid cancer . 
Background
Material and Methods
Publication search
Inclusion criteria and data extraction
Statistical analysis
Results
Study characteristics
Quantitative data synthesis
Discussion
Conclusions