1. Abstract Purpose: Obesity is associated with aggressive pathological featuresandpoorclinicaloutcomesinbreastandprostatecancers. However, the associations between excess weight and prognostic factorsforthyroidcancerareuncertain.Thisstudyaimedtoevaluatetheassociationsbetweenbodymassindex(BMI)andseverity according of classification of thyroid cancer. Methods: Retrospective analysis of 4485 patients with thy- roid cancer was performed. Patients were grouped according to BMI(underweight,normalweight,overweightandobesity)-based WorldHealthOrganizationstandardizedcategories.Clinicopathological factors were analyzed and compared between normal and other groups. Results:According to the results, 3789 patients were women (84.5%)andmeanagewas47.1years.4338patients(96.7%)were diagnosedwithPTC.FTCwere115(2.6%),MTAware24(0.5%), ATC were 5(0.1%). There were no significant associations be- tween BMI quartiles and Multifocality, cervical lymph node me- tastasis, or distant metastasis. Higher BMI were significantly as- sociated with extrathyroidal extension of PTC (P < 0.001). And higher BMI were significantly associated with advanced TNM stage (P=0.005). Conclusion:IncreasedBMImightelevatetherisksofaggres- sive clinicopathological features of PTC, such as extrathyroidal invasionandadvancedTNMstage.However,therewerefewcases exceptforPTC,whichmadeitdifficulttofindstatisticallysignificantresults.Toconfirmthisresult,furtherstudieswithlong-term
Keywords: Obesity; Bodymassindex; Thyroid carcinoma
2. Introduction Recently,theincidenceofthyroidcancerhasbeengrowingworld- wide[1].Higherprevalenceofthyroidcancercanbeexplainedin partbythefactthatdevelopmentanduseofneckultrasonography andultrasound-guidedfine-needleaspirationhaveledtoincreased diagnosticrateforasymptomaticthyroidcancer[2].Additionalas- pects, such as changes in exposure to environmental factors, may also play a role in explaining such increase in prevalence. However,consideringthatincreaseinprevalenceofthyroidcancer coincidedwithincreasednumberofearlycancerwithsmalltumor size, aswell asvarioustumor sizesand stages, it issuspected that thereareotherunidentifiedfactorsbesidesadvancesindiagnostic tools [3].The main risk factors for thyroid cancer are exposure to ionizingradiation,ahistoryofbenignthyroiddisease,andafamily history of thyroid cancer [4, 5, 6]. Overweight and obesity, ex- pressedasa highBMI,are possibleriskfactorsforthyroid cancer Obesityisassociatedwithonsetandprogressionofmanycancers, including those of esophagus, colon, kidney, breast, skin, rectum, and gallbladder [7]. Obesity is the second most common, pre- ventable, and modifiable cause of carcinogenesis, after smoking, thereisworldwidevariationthatisdependentonthedifferentinci- dences of obesity [8].Although obesity is a known risk factor for carcinogenesis it does not seem to equally impact on all types of cancer.However,therearefewreportsontherelationshipbetween obesityandthyroidcancerandtheunderlyingmechanismislarge- ly unknown [9 -12]. clinicsofoncology.com A review of studies on the association between thyroid cancer and BMI showed that recent studies are reporting that obesity is one of the factors considered to cause increase in thyroid cancer [13,14].Inaddition,someretrospectivestudieshavereportedthat increase in BMI is associated with aggressive clinicopathological featuresinpatientswithpapillarythyroidcarcinoma[15].However,therelationshipbetweenobesityandpoorprognosisassociated with thyroid cancer is still controversial [16], and while the basis for the correlation between excessive weight and malignant thyroid tumor has not yet been completely identified, the traditional riskfactorsofthyroidcancerstillremainradiationexposure,high iodine intake, and family history of thyroid cancer [17]. For future evident on the potential negative effect of obesity on thyroid cancer,itisdeterminedthatclinicalinterventionincludingweight lossprogramsforoverweightandobesepeopleandthyroidcancer screening guidelines would play an important role. Accordingly, the present study aimed to investigate the correlation between clinicopathological parameters and being overweight in relationtothyroidcancertousethefindingstoidentifythecorrelationbetweenBMIandcanceraggressivenessinrelationtothyroidcancer.
3. Methods The study population included4, 485patientswhoreceivedsurgicaltreatmentatKosinUniversityGospelHospitalbetweenJanuary 2005 and December 2015 and were subsequently diagnosed with thyroidcancer.Allmedicalrecordsofthesepatients,includinghistopathologicalresults,wereretrospectivelyanalyzed.BMIofeach patientwascalculatedusingtheheightandweightmeasuredatthe timeofadmissionforthesurgery.UsingthestandardBMIcategoriesfromtheWorldHealthOrganization(WHO),thepatientswere dividedintofourgroups:underweight(18.5),normal(18.5∼24.9), overweight(25.0∼29.9),andobese(≥30.0).[18].Theclinicopathological factors of the normal group were compared to those of other groups, while tumor size, multifocality, lymph node (LN) metastasis, advancedTNM staging, and recurrence were compared asfactorssuggestingaggressivenessofthetumor.AdvancedTNM staging was divided according to the classification system given by theAmerican Joint Committee on Cancer (AJCC; 8th edition) [19],andstages1and2werecomparedandanalyzedagainststages3and4,representingadvancedcancer.Recurrencewasdefined asnewpathologicallyconfirmedlesioninapatientwhohadbeen determined to be in remission during the follow-up observation period.Univariateanalysesincludingchi-squaretestandone-way analysis of variance (ANOVA) were performed to determine the significance between BMI and the variables, while multivariate analysis was performed on the factors suggesting cancer aggressiveness.Alogisticregressionmodelwasusedtoestimatetheodds ratio (OR) and 95% confidence interval (CI), while adjusted OR was calculated by adjusting for age, gender, and TSH value. All statisticalanalyseswereperformedusingSPSS17.
4. Results Amongatotalof4,485patients,therewere3,789females(84.5%) and 696 males (15.5%). The mean age was 47.1 years (14∼82 years)andmeanBMIwas24.0±3.3(15.0∼41.2).BasedonBMI categories,thepatientsweredividedintotheunderweight(n=112, 2.5%), normal (n=2,824, 63.0%), overweight (n=1,341, 29.9%), and obese (n=208, 4.6%) groups. BasedonPathology,Therewere4,338(96.7%)patientswithpapillary thyroid cancer, 115(2.6%) patients with Follicular thyroid carcinoma,24(0.5%)patientswithMedullarythyroidcarcinoma, 5 (0.1%) patients with Anaplastic thyroid carcinoma. The mean tumor size was 12.1 mm (2∼72mm), there were 2,602 cases(58.0%)withtumorsize≤1cmand1,470cases(32.8%)had multifocality.ExtrathyroidinvasionandLNmetastasiswasfound in 2,100 cases (46.8%) and 1,824 cases (40.7%), respectively, where LN metastasis involved the central neck LN in 1,430 cases (31.9%) and lateral neck LN in 394 cases (8.8%). In advanced TNM staging, the number of cases classified as stage 1, 2, 3, and 4was2,768(61.7%),84(1.9%),1,435(32.0%),and197(4.4%), respectively, while in adjusted TNM staging for statistical analysis, there were 2,853 cases (63.6%) of stages 1 and 2 and 1,632 cases (36.4%) of stages 3 and 4. The mean follow-up period was 1,721±464.2days,andduringthefollow-upperiod,therewere88 cases (2.0%) of recurrences. Of those cases, recurrence found in the central neck LN, lateral neck LN, and contralateral thyroid in 3cases(3.4%),62cases(70.5%),and23cases(26.1%),respectively(Table1). There were few cases except for PTC, which made it difficult to find statistically significant results (Table 2).
5. Discussion IncreasedBMIhasbeenassociatedwithahighercancerincidence forseveralmalignancies,includingthyroidcancer[9].Inaddition, obesity has been reported to be associated with poor pathological prognostic correlates and the development of recurrence and metastases for several cancer types, including breast, prostate, and colon cancers [7]. Obesity can cause impairment in the metabolic processwithinthebodyandalsocauseabroadrangeofendocrine abnormalities involving the pituitary, pancreas, gonad, adrenal glands, and thyroid glands [20]. Recent studies are also reporting that obesity is associated with increased incidence of thyroid cancer [21]. Kim et al. [21]. Performed a case–control study in which the authors hypothesized that overweight and obesity would be associated with higher risk of PTC in an adolescent Korean population (BMI≥25 at age 18 years). They included 1549 cases and selected 15 490 controls matched 1: 10 for age (±5 years) and sex who were all more than 20 years age. After adjustment for potential confounders, a BMI at least 25 at the age of 18 was associated with a higher risk of developing PTC compared with those with BMI less than 23 [hazard ratios 4.31 (3.57–5.22)], both in men [hazard ratios 6.65 (4.76–9.27)] and women [hazard ratios 3.49 (2.74–4.43)] [22]. In an analysis conducted in the US, increase in the incidence of thyroid cancer according to increase in BMI was observed in both malesandfemales,whileastudyconductedintheFrenchPolyne- sian region with relatively high prevalence of thyroid cancer also confirmed such correlation. Especially in the study from French Polynesian region, BMI ≥25 in those aged 18 years or older, the periodwhentheyareenteringadulthood,showedhighprobability of thyroid cancer (OR 6.2, P＜0.01) [23]. OtherreportshavealsoindicatedthathigherBMImanifestsmore aggressive forms of cancer, including breast cancer. [21]According to Harari et al. [21], in terms of thyroid cancer, obese patients showed higher stage and more aggressive form of PTC. In their study,thepercentageofthoseinstage3or4amongnormal,overweight, obese, and morbidly obese groups was 13.2%, 22.7%, 24.3%, and 35.7%, respectively, while the relative risk in overweight, obese, and morbidly obese groups was 1.94, 2.11, and 3.67, respectively (P=0.04) [24]. According to a report by Feng et al. [24] of 417 papillary thy-roid cancer patients, 31.6% were overweight and 6% were obese. After adjusting for clinicopathological features, overweight was associatedwithvascularinvasion[hazardratios3.9(1.06–14.31)], while obesity was associated with ETE [hazard ratios 6.14 (1.81– 0.89)] and vascular invasion [hazard ratios 9.19 (1.73–51.71)], when compared with those who were normal weight. No statistically significant differences were reported in PTC recurrence among the BMI groups [25]. In an analysis by Kim et al. [25] BMIatleast25atage18yearswaspositivelyassociatedwithETE [hazard ratios 1.5 (1.06–2.12)] and tumor stage at least 2 [hazard ratios1.94(1.03–3.65)],butnotwithlymphnodestageatleast 1 or BRAF V600E mutation positivity compared with those with BMI less than 23. [22]. Similar results were reported by Grani et al. [22], who investigated the association between overweight or obesity and aggressive features of DTC among 432 patients in Italy [n=154 (35.6%) overweight and n=86 (19.9%) obese]. Obese patientsweresignificantlymorefrequentlymaleandoldage.Most PTCs were at low-risk (67.8%) and the majority had never been treated with 131I (69.2%). In their analysis, BMI as a categorical variable was not associated with aggressive DTC features, while patientswithETEhadasignificantlyhigherBMIwhenevaluated as a continuous variable [26].
6. Conclusions RetrospectiveanalysisoftheassociationbetweenBMIandcancer aggressiveness in patients with PTC showed that the obese group showedhigherrateofmultifocalityandextrathyroidinvasionthan the normal group.Although various cause may play a role in the onset of PTC, maintaining BMI at an appropriate level may be a methodforpreventingtheonsetofPTCwithmoreaggressivetendencies,suchasmultifocalityandextrathyroidinvasion.However there were few cases except for PTC, which made it difficult to find statistically significant results.To confirm this result, further studies with long-term follow-up and more patients are required.
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