obesity is a well - established risk factor for obesity - related cancers , especially for crc .
the prevalence of obesity has doubled world - wide 1980 and at least 500 million people are classified as obese ( body mass index [ bmi ] 30 kg / m ) .
lifestyle - based behavioral and pharmacological interventions for weight loss remain the major approaches to obesity prevention and management [ 35 ] , but with limited success . surgical treatment for obesity ( bariatric surgery )
should be considered in patients with bmi > 40 kg / m or for those have other significant obesity - related comorbidities but bmi 3540 kg / m .
bariatric surgery has been shown to be successful in achieving significant sustained weight loss with low operative mortality and proven safety in older ( > 55 years ) obese patients [ 68 ] .
weight loss after bariatric surgery yields important health benefits , including resolution of type 2 diabetes in most treated patients and lower total mortality , attributed mainly to reduced incidence of major cardiovascular events and cancer overall . a meta - analysis of 21 observational studies from ma et al .  
indicated that obesity is associated with increased thyroid cancer risk , except for medullary thyroid cancer .
given the role of overweight and obesity in increasing obesity - related cancers risk , one might expect that weight loss achieved through bariatric surgery would result in reduced risk of obesity - related cancers .
we performed a systematic review and meta - analysis aiming to summarize the relationship between bariatric surgery and incidence of obesity - related cancers .
our systematic review was conducted according to cochrane and the centre for reviews and dissemination guidelines and is reported according to prisma guidelines [ 1214 ] .
pubmed , embase , web of science , and google scholar were independently searched by 2 investigators ( xiang - wu yang and shai - hong zhu ) to identify potential eligible studies .
in addition , the reference lists of relevant reviews and studies retrieved were manually searched to identify additional eligible studies .
the above databases were searched using a combination of indexed terms and text word searches of title , abstract , and keywords .
the following index words were used :  overweight or obese ,   behavioral or lifestyle - based or pharmacological or bariatric surgery or weight loss  and  obesity - related cancer or cancer . 
this search strategy was adapted for use with other databases , and further details are available on request .
two reviewers ( peng - zhou li and li - yong zhu ) performed the initial screening of titles and abstracts against the inclusion and exclusion criteria to identify potentially relevant papers .
full - text versions of potentially relevant papers identified from the initial screening were retrieved . in cases of disagreement in the initial screening stage , full text of the articles involved was retrieved . where multiple articles from the same study were found , only the report with the longest follow - up period was included .
both reviewers screened all full - text articles to generate the final list of articles to be included in the systematic review and meta - analysis .
the following data were extracted using a standardized form : study design , country of origin , period of study , follow - up period , baseline characteristics of population , inclusion / exclusion criteria , description of the intervention , and any relevant outcome measures ( as described above ) .
quality assessment of non - randomized studies was performed using the newcastle - ottawa scale ( nos ) .
we combined studies reporting obesity - related cancers incidence using a random- or fixed - effects meta - analysis .
heterogeneity levels in these studies were quantified using the i statistic , and the 95% confidence interval ( ci ) for i was calculated using the higgins et al . method .
statistical analyses were performed using the review manager ( revman ) computer program , version 5.3 .
pubmed , embase , web of science , and google scholar were independently searched by 2 investigators ( xiang - wu yang and shai - hong zhu ) to identify potential eligible studies .
in addition , the reference lists of relevant reviews and studies retrieved were manually searched to identify additional eligible studies .
the above databases were searched using a combination of indexed terms and text word searches of title , abstract , and keywords .
the following index words were used :  overweight or obese ,   behavioral or lifestyle - based or pharmacological or bariatric surgery or weight loss  and  obesity - related cancer or cancer .
 this search strategy was adapted for use with other databases , and further details are available on request .
two reviewers ( peng - zhou li and li - yong zhu ) performed the initial screening of titles and abstracts against the inclusion and exclusion criteria to identify potentially relevant papers .
full - text versions of potentially relevant papers identified from the initial screening were retrieved . in cases of disagreement in the initial screening stage , full text of the articles involved was retrieved . where multiple articles from the same study were found , only the report with the longest follow - up period was included .
both reviewers screened all full - text articles to generate the final list of articles to be included in the systematic review and meta - analysis .
the following data were extracted using a standardized form : study design , country of origin , period of study , follow - up period , baseline characteristics of population , inclusion / exclusion criteria , description of the intervention , and any relevant outcome measures ( as described above ) .
quality assessment of non - randomized studies was performed using the newcastle - ottawa scale ( nos ) .
we combined studies reporting obesity - related cancers incidence using a random- or fixed - effects meta - analysis .
heterogeneity levels in these studies were quantified using the i statistic , and the 95% confidence interval ( ci ) for i was calculated using the higgins et al . method .
statistical analyses were performed using the review manager ( revman ) computer program , version 5.3 .
the searches generated a total of 142 publications , of which titles and abstracts were screened .
five studies that met our inclusion criteria were included in the present review and meta - analysis [ 1822 ] .
no studies reporting on obesity - related cancers outcomes after bariatric surgery were excluded on the basis of study design or quality .
they reported on obesity - related cancers incidence in a total study population of 26 331 individuals after bariatric surgery and 82 903 obese controls ( table 1 ) [ 1822 ] .
all studies had a predominance of female subjects ( mean 79% and 66.8% in the bariatric surgery and control groups , respectively ) .
adams et al .   identified controls with a self reported bmi 35 kg / m on their driver s license identification application .
the other 4 included studies identified the control population using the diagnosis of morbid obesity as recorded on respective data registries [ 1822 ] .
the study by adams et al .   was unique in reporting baseline bmi data and using bmi to match the bariatric surgery and control groups .
none of the studies specified the treatment ( if any ) given to the control groups .
gastric bypass was either the sole or the most commonly employed surgical procedure used in the included studies ( table 1 ) .
follow - up bmi data was reported in only 1 study and this was for the bariatric surgery group only ( mean bmi reduction 31.9% ; 95% ci , 31.132.2 ) .
reported a lower crc risk in the bariatric surgery group compared with the non - surgically treated controls ( unadjusted rr 0.32 ; 95% ci , 0.0761.313 , p=0.063 ) .
adams et al .   also reported reduced crc risk in the bariatric surgery group ( hr 0.70 ; 95% ci , 0.431.15 , p=0.15 ) .
four of the studies had high scores ( 79 , max score=9 ) using the nos tool , whereas the other had a lower score ( 4 ) .
there were too few studies to perform a funnel plot analysis of potential publication bias .
data from the 5 bariatric surgery studies were included in a meta - analysis to estimate the overall effect of surgery on obesity - related cancers diagnosis using a random - effects model ( figure 2 ) .
subgroup analysis was carried out to explore the potential influence of different cancer types and found that the estimated data were significantly altered by colorectal cancer ( p=0.57 ) ( figure 3 ) .
the meta - analysis revealed that weight loss after surgery was associated with significantly ( p=0.0004 ) lower risk of subsequent obesity - related cancers diagnosis ( or 0.43 ; 95% ci , 0.270.69 ) ( figure 2 ) .
the meta - analysis also showed that weight loss after surgery was associated with significantly ( p=0.02 ) lower risk of subsequent crc diagnosis ( or 0.76 ; 95% ci , 0.610.95 ) ( figure 4 ) .
they reported on obesity - related cancers incidence in a total study population of 26 331 individuals after bariatric surgery and 82 903 obese controls ( table 1 ) [ 1822 ] .
all studies had a predominance of female subjects ( mean 79% and 66.8% in the bariatric surgery and control groups , respectively ) .
adams et al .   identified controls with a self reported bmi 35 kg / m on their driver s license identification application .
the other 4 included studies identified the control population using the diagnosis of morbid obesity as recorded on respective data registries [ 1822 ] .
the study by adams et al .   was unique in reporting baseline bmi data and using bmi to match the bariatric surgery and control groups .
none of the studies specified the treatment ( if any ) given to the control groups .
gastric bypass was either the sole or the most commonly employed surgical procedure used in the included studies ( table 1 ) .
follow - up bmi data was reported in only 1 study and this was for the bariatric surgery group only ( mean bmi reduction 31.9% ; 95% ci , 31.132.2 ) .
reported a lower crc risk in the bariatric surgery group compared with the non - surgically treated controls ( unadjusted rr 0.32 ; 95% ci , 0.0761.313 , p=0.063 ) .
adams et al .   also reported reduced crc risk in the bariatric surgery group ( hr 0.70 ; 95% ci , 0.431.15 , p=0.15 ) .
four of the studies had high scores ( 79 , max score=9 ) using the nos tool , whereas the other had a lower score ( 4 ) .
there were too few studies to perform a funnel plot analysis of potential publication bias .
data from the 5 bariatric surgery studies were included in a meta - analysis to estimate the overall effect of surgery on obesity - related cancers diagnosis using a random - effects model ( figure 2 ) .
subgroup analysis was carried out to explore the potential influence of different cancer types and found that the estimated data were significantly altered by colorectal cancer ( p=0.57 ) ( figure 3 ) .
the meta - analysis revealed that weight loss after surgery was associated with significantly ( p=0.0004 ) lower risk of subsequent obesity - related cancers diagnosis ( or 0.43 ; 95% ci , 0.270.69 ) ( figure 2 ) .
the meta - analysis also showed that weight loss after surgery was associated with significantly ( p=0.02 ) lower risk of subsequent crc diagnosis ( or 0.76 ; 95% ci , 0.610.95 ) ( figure 4 ) .
to the best of our knowledge , this is the most complete systematic assessment and meta - analysis of the effects of bariatric surgery on the subsequent risk of obesity - related cancers .
our meta - analysis of data from 5 observational studies involving 109 234 individuals followed for 512.3 years ( where reported ) revealed that bariatric surgery is associated with a 57% lower ( p=0.0004 ) subsequent risk of obesity - related cancers diagnosis .
no studies reporting on obesity - related cancers outcomes after bariatric surgery were excluded on the basis of study design or quality ; therefore , these results summarize the evidence currently available . our meta - analysis also revealed that bariatric surgery is associated with a 24% lower ( p=0.02 ) subsequent risk of crc diagnosis .
no studies reporting on crc - related outcomes after bariatric surgery were excluded on the basis of study design or quality ; therefore , these results summarize the evidence currently available .
obesity is a complex multi - system health problem and it is acknowledged that a  one system fits all 
mechanism is unlikely . given that bariatric surgery reduces inflammatory markers , reduces genomic damage , and/or enhances antineoplastic responses , one would expect a reduction in obesity - related cancers risk after bariatric surgery [ 2426 ] .
the major limitation of this review is the small number of studies that met our inclusion criteria .
the studies reviewed here , all on bariatric surgery , were observational and results from meta - analyses of observational studies should be treated with caution .
such rcts would be difficult to conduct due to requiring many participants with lengthy follow - up to achieve sufficient power to detect any effect .
the studies included in our meta - analysis had different lengths of follow - up . because of insufficient data in the primary studies , we were unable to perform regression analysis to investigate the effect of length of follow - up .
however , the consistency in outcomes across the 5 studies suggests that the heterogeneity in duration of follow - up is unlikely to have biased the outcome .
overweight or obese patients undergoing bariatric surgery are more likely to be motivated to lead a healthier lifestyle than untreated obese controls .
in addition , 4 of the 5 studies included in our meta - analysis identified controls using the diagnosis of morbid obesity , which is an approach that could have selected less healthy obese individuals as controls .
many environmental and lifestyle factors influence the risk of obesity - related cancers ; therefore , it is possible that factors other than weight loss following bariatric surgery are responsible for the apparently protective effect against obesity - related cancers observed in the present study . despite attempts to adjust for some confounders by design in some of the included studies ( e.g. , use of age- and sex - matched controls ) , potential confounding factors such as cigarette smoking and alcohol drinking were not adjusted for in any of the included studies . despite the inability to adjust for smoking or alcohol use because of a lack of direct data , derogar et al
. attempted to examine possible effects by performing a sensitivity analysis in which those with smoking- and alcohol - related diagnoses were excluded from the analysis . a lower proportion of individuals had such a diagnosis in the bariatric surgery than in the control group ( 9.7% vs. 15.0% , respectively ) , but this exclusion did not change their findings .
a study by the same group has shown a hyperproliferative state in rectal mucosal biopsies 6 months after rygb when compared to obese controls .
the hypothesis states that the predominantly  malabsorptive  bariatric procedures , such as rygb , may expose the colorectal mucosa to harmful luminal contents and , given the latency in crc carcinogenesis , this effect becomes more apparent with time after surgery .
there is a lack of high - quality evidence about the effects of bariatric surgery on the subsequent risk of obesity - related cancers . to date , all relevant data are from non - randomized observational studies . our meta - analysis of observational studies has shown that bariatric surgery ( predominately using roux - en - y gastric bypass ) was associated with 57% lower obesity - related cancers risk and 24% lower crc risk .
well - designed prospective clinical studies of the long - term effects of weight loss interventions , including bariatric surgery , on obesity - related cancers risk are required .
 backgroundthe aim of this meta - analysis was to investigate possible relationships between bariatric surgery and incidence of obesity - related cancers . 
 obesity is an established risk factor for obesity - related cancers but the effects of bariatric surgery on incidence of obesity - related cancers are uncertain.material/methodswe searched 4 electronic databases to identify eligible studies : pubmed , embase , web of science , and google scholar . 
 five observational studies were eligible and included in this meta - analysis . 
 random - effects or fixed - effects odds ratio ( or ) and its corresponding 95% confidence interval ( ci ) were pooled.resultsmeta-analysis of these 5 observational studies revealed that bariatric surgery was associated with a significantly ( p=0.0004 ) reduced incidence of obesity - related cancers ( or=0.43 , 95%ci , 0.270.69 ) when compared with control individuals . 
 pooled estimated data showed that bariatric surgery is associated with a 24% lower colorectal cancer ( crc ) risk . 
 no publication bias was detected by egger s or begg s tests.conclusionsalthough bariatric surgery may significantly reduce incidence of obesity - related cancers , considering the limitations of these included studies , these findings should be confirmed by further well - designed studies . 
Background
Material and Methods
Search strategy and study selection
Data extraction and quality assessment
Statistical analysis
Results
Study characteristics
Study quality and publication bias
Quantitative results (meta-analysis)
Discussion
Conclusions