IJC International Journal of Cancer

Transcription

1 IJC International Journal of Cancer Association between height and thyroid cancer risk: A meta-analysis of prospective studies Zhaohai Jing 1 *, Xu Hou 1 *, Ying Liu 1, Shengli Yan 1, Robin Wang 1,2, Shihua Zhao 1 and Yangang Wang 1 1 Department of Endocrinology, Affiliated Hospital of Qingdao University, Qingdao, , China 2 Department of Medicine, Second Military Medical University, Shanghai , China While several epidemiological studies have investigated the relationship between height and risk for thyroid cancer, the results were inconsistent. In the present study, a systematic review and meta-analysis of prospective studies was conducted to assess the impact of height on thyroid cancer risk. Online databases were searched up to December 30, 2014, for prospective studies on the association between height and thyroid cancer risk. Pooled relative risks (RRs) and 5% confidence intervals (CIs) were calculated using a random-effects model of meta-analysis. In all, 11 articles were included in this meta-analysis, including 15 prospective studies, containing 6,65,53 participants and 7,062 cases of thyroid cancer. By comparing the highest versus the lowest categories of height, we reported that risk of thyroid cancer was increased with height in both men (summary RR , 5%CI , p ) and women (summary RR , 5%CI , p < 0.001). The summary RR of thyroid cancer per 5-cm increase in height was 1.16 (5%CI , p < 0.001). The results were similar among men (per 5-cm increase RR , 5%CI , p ) and women (per 5-cm increase RR 5 1.1, 5%CI , p < 0.001). No obvious risk of publication bias was observed. Our meta-analysis provides strong evidence for a dose response relationship between height and risk of thyroid cancer in both men and women. Thyroid cancer is the most common malignant tumor of the endocrine system, accounting for about 1% of all cancers. 1 The incidence of thyroid cancer is.1 per 100,000 worldwide. 2 The incidence of thyroid cancer has been rising over the recent years, which may be primarily due to more sensitive diagnostic techniques and increased number of cases induced by enhanced environmental exposure. 3 It has been known that multiple factors are involved in thyroid carcinogenesis, such as genetic and environmental factors. 4,5 Identification of risk Key words: thyroid cancer, height, meta-analysis Abbreviations: CI: confidence interval; IGF-1: insulin-like growth factor-1; NOS: Newcastle Ottawa scale; RR: relative risk Z.J., B.W., Y.W. and S.Z. conceived the study aims and design, contributed to the systematic review, interpreted the results and drafted the article. Z.J., Y.L., X.H. and S.Y. performed data extraction, completed the analyses and revised the article. All authors discussed the results and reviewed and edited the article *Z.J. and X.H. contributed equally to this study DOI: /ijc.247 History: Received 2 Dec 2014; Accepted 12 Feb 2015; Online 1 Feb 2015 Correspondence to: Shihua Zhao, Department of Endocrinology, Affiliated Hospital of Qingdao University, Qingdao , China, Tel: , Fax: , zhaosh@ qdumh.qd.sd.cn or Yangang Wang, Department of Endocrinology, Affiliated Hospital of Qingdao University, Qingdao , China, Tel: , Fax: , wangyg166@126.com factors for thyroid cancer can help us get a better understanding of the pathogenesis of thyroid carcinogenesis and develop more effective preventive interventions for high-risk population. Currently, the well-known risk factor for thyroid cancer is exposure to ionizing radiation. 4 Other possible risk factors for thyroid cancer such as obesity and diabetes have also been identified. 6 Previous epidemiological studies have suggested that taller people have an increased risk for cancer, such as prostate cancer, pancreatic cancer, ovarian cancer and breast cancer, and thus height has been proposed as a risk factor of cancer in the past decade. 11 There were also a number of studies assessing the relationship between height and risk for thyroid cancer, but the results were inconsistent. 7,14 21 Hereby we have performed a systematic review and metaanalysis of prospective studies to get a more precise assessment of the impact of height on thyroid cancer risk. Material and Methods Literature search and study selection PubMed, Web of Science and Embase were searched for prospective studies assessing the association between height and risk of thyroid cancer. In the literature search, there was no language limitation and no regional limitation. The following search terms were employed to retrieve the relevant literatures in the databases listed previously: ( height or body size ) and ( thyroid cancer, thyroid carcinoma or thyroid tumor ) and ( prospective, or longitudinal ). The search time was up to December 30, The references of included studies and relevant reviews were also checked for eligible studies.

2 Jing et al. 145 What s new? The taller a person is, the greater his or her risk for thyroid cancer may be, although not all studies on the subject have reached that same conclusion. To gain a clearer picture of the relationship between height and thyroid cancer, the present meta-analysis took into consideration data from 15 prospective studies. The findings of the analysis corroborate the existence of an association, whereby thyroid cancer risk increases with increasing height, in both men and women. Although the mechanistic basis for the association awaits elucidation, pathways centering on insulin-like growth factor-1 (IGF-1), which influences growth, are implicated. To be included in the meta-analysis, the studies must meet the following criteria: (i) prospective studies; (ii) assessing the relationship between height and risk of thyroid cancer and (iii) reporting relative risks (RRs) and 5% confidence intervals (5%CIs) for thyroid cancer risk. Retrospective, cross-section and case-control studies were all excluded. Studies with overlapping data were also excluded. Data extraction and quality assessment Two investigators performed the data extraction independently. If there was any disagreement between the two investigators, it was resolved by discussion until consensus was reached between the investigators. The following data were extracted from each included study: publication year, first author s name, study design, country, number of participants, number of cases, time of follow-up, gender distribution, types of thyroid cancer, confounding factors and RRs with corresponding 5%CIs. For studies providing RRs with different adjusted factors, the most adjusted RRs were used in the meta-analysis. The quality of prospective studies was assessed using the Newcastle Ottawa scale (NOS), 22 generating a maximum of nine stars to each study, including four stars for the selection of participants, two stars for the comparability of participants and three stars for the assessment of outcomes. Quality was assigned according to the scores so that 7 stars indicated high quality, 4 6 stars for middle quality and 0 3 stars for low quality. The scores were determined by two investigators and if there was any disagreement between the two investigators, it was resolved by discussion until consensus was reached. Data analysis We first determined the summary RRs of thyroid cancer comparing the highest versus the lowest categories, and then calculated the summary RRs of thyroid cancer per 5-cm increase in height. Statistical heterogeneity between studies was evaluated with the I 2 statistic method where I 2 [mt]50% indicated obvious heterogeneity. Since there was obvious difference in the categories of height and other baseline characteristics, we calculated the pooled RRs and 5%CIs using the random-effects model of meta-analysis. Subgroup analysis was performed by gender (men or women), thyroid cancer histology (differentiated thyroid cancer or all types of thyroid cancer) and age (adults or nonadults). Sensitivity analysis was performed by omitting one single study by turns to test the variability of the pooled RRs. Publication bias was assessed by visual inspection of the funnel plot. Asymmetry of the funnel plot was further assessed using Egger s regression test. All statistical analyses were performed using STATA version A two-tailed p < 0.05 was considered statistically significant. Results Study characteristics Of the 223 individual studies identified from our literature search, 205 were excluded initially after reviewing titles and abstracts, and 1 studies were thoroughly assessed by full-text reading, which further excluded another seven studies. Finally, 11 studies 7,14 21 were included into this metaanalysis, including 15 prospective studies. 7,14 21 The selected studies involved a total of 6,65,53 participants and 7,062 cases of thyroid cancer (Table 1). The main characteristics of the selected studies were shown in Table 1. Within the selected studies, there were four studies from United States,,14,17,1 one study from Norway, 7 one study from Korea, 15 one study from France, 16 one study from Canada, 1 one study from Denmark, 21 one study from Israel 20 and one study from ten European countries. The time of follow-up in these studies ranged from.7 to 3.6 years (Table 1). According to the quality criteria, all of the 11 studies were of the high-quality category (Table 1). Seven studies investigated the relationship between height and thyroid cancer in women, 7,,15 1,20 five studies investigated that in men 7,,15,17,20 and one study in mixed population. 14 Among the 11 studies, focused on all types of thyroid cancer, 7,,14,15,17 21, and 2 on differentiated thyroid cancer (DTC).,16 Eight studies reported the RRs of thyroid cancer comparing the highest versus the lowest categories of height, 7,,14 1,20 whereas seven studies reported RRs of thyroid cancer per 5-cm increase in height. 7,15,1,1,21 Height and risk of thyroid cancer Obvious heterogeneity was present among the eight studies 7,,14 1,20 reporting RRs comparing the highest versus the lowest categories of height (I %). Meta-analysis of these studies 7,,14 1,20 showed that larger height was associated with increased risk of thyroid cancer (summary RR 5 1.4, 5%CI

3 146 Height and thyroid cancer Table 1. The main characteristics of those 11 prospective studies included into the meta-analysis Study Country Design Participants Cases Iribarren United et al. 14 States 204,64 persons (aged 10 at baseline, 54% females) Follow-up (year) Height range Adjusted factors Quality All heights Age, gender, race, education, smoking, self-reported personal history, family history of thyroid disease, BMI, weight gain and occupational exposures. Engeland Norway et al. 7 2,001,727 persons (aged years, 51.% females) 3, All heights Age at measurement, year of birth and BMI. Sung Korea et al. 15 7,7 persons (40 64 years of age at baseline, 4.1% females) 43.7 Men ( cm); women ( cm) Age, body mass index, cigarette smoking, alcohol consumption and regular exercise, monthly salary, occupation and area of residence. Meinhold United et al. 17 States 0,713 radiologic technologists (76.6% females) All heights Birth year, smoking status, body mass index, number of personal radiographs to the head or neck, cumulative occupational radiation dose and medical history of benign thyroid conditions. Clavel- Chapelon et al. 16 France 1,0 women with the age of years at inclusion in All heights Age, and stratified on year of birth, history of goiter or thyroid nodules, smoking status, iodine. Kitahara United et al. States Five prospective 413,7 women and 434,53 men with mean age at a baseline of 5.2 years 1, All heights Education, race, marital status, smoking, alcohol intake and (where appropriate) and sex Kabat United et al. 1 States 144,31 postmenopausal women (aged 50 and 7) All heights Age, age at first full-term pregnancy, education, pack-years of smoking, alcohol intake, MET-hours/week, history of benign thyroid disease, OS/CT and randomization status in CT Rinaldi Ten et al. European countries 343,765 female and 146,24 male (aged 35 6 years, 70.1%females) 566 Appr. 10 All heights Center and age at recruitment, age and smoking.

4 Jing et al. 147 Table 1. The main characteristics of those 11 prospective studies included into the meta-analysis (Continued) Follow-up (year) Height range Adjusted factors Quality Study Country Design Participants Cases All heights Age at entry, menopausal status and years of education, BMI.,256 women (aged 40 5 years) Kabat Canada et al. 1 Age as the time metric, BMI, birth weight Women ( cm); men ( cm) 321,05 children (aged 7 to 13 years) Kitahara Denmark et al All heights Year of birth, country of origin and years of schooling are for the model with height introduced in cm. 1,624,310 participants (aged 16 1 years) Farfel Israel et al , p < 0.001; Fig. 1). Subgroup analysis by gender showed that, by comparing the highest versus the lowest categories of height, the risk of thyroid cancer was increased in both men 7,,15,17,20 (summary RR , 5%CI , p ) and women 7,,15 1,20 (summary RR , 5%CI , p < 0.001). Subgroup analysis by thyroid cancer pathology classification showed that, by comparing the highest versus the lowest categories of height, the risk of thyroid cancer was increased in both DTC,16 (summary RR , 5%CI , p ) and all types of thyroid cancer 7,,14,15,17 21 (summary RR 5 1.4, 5%CI , p <0.001). Subgroup analysis by age showed that, by comparing the highest versus the lowest categories of height, the risk of thyroid cancer was increased in both adults 7,,14 1 (summary RR , 5%CI , p < 0.001) and nonadults 20 (summary RR , 5%CI , p < 0.001). Obvious heterogeneity was observed among the seven studies 7,15,1,1,21 reporting RRs of thyroid cancer per 5-cm increase in height (I %). Meta-analysis of these studies showed that the summary RR of thyroid cancer per 5-cm increase in height was 1.16 (5%CI , p < 0.001; Fig. 2). The results were similar in men 7,15,21 (per 5-cm increase RR , 5%CI , p ) and women 7,15,1,1,21 (per 5-cm increase RR 5 1.1, 5%CI , p < 0.001; Fig. 2). Publication bias Visual inspection of the funnel plot did not detect obvious asymmetry. The Egger s regression asymmetry test showed no evidence of publication bias for the association between height and thyroid cancer risk (p 5 0.7). Thus, no obvious risk of publication bias was observed in the meta-analysis. Discussion Although some epidemiological studies have investigated the relationship between height and the risk of thyroid cancer, the results were far from consistent. In the studies included in the present meta-analysis, five reported the absence of statistically significant association between height and risk of thyroid cancer (Figs. 1 and 2). The present systematic review and meta-analysis of published observational study evaluated the influence of height on risk of thyroid cancer in 11 studies, including 6,65,53 participants and 7,062 cases of thyroid cancer. While previous studies have suggested that height might be a risk factor for carcinogenesis, the present meta-analysis and subgroup analysis by gender indicate the presence of a strong association between height and risk of thyroid cancer in both men and women. Our meta-analysis also suggested a dose response relationship between height and risk of thyroid cancer in both men and women. The summary RR of thyroid cancer per 5-cm increase in height was The results were similar in men (per 5-cm increase RR ) and women (per 5-cm increase RR < 0.001). The dose response relationship above

5 14 Height and thyroid cancer Figure 1. Forest plot showing the relationship between height and risk of thyroid cancer by comparing the highest versus the lowest categories of height. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.] further strengthened the association between height and risk of thyroid cancer. A number of studies have reported correlation between height and different types of cancer. Jane Green s 11 study containing 1,27,124 participants from UK showed that the summary RR was 1.14 (5%CI ) per 10 cm increase in height in all cancers, and that height was associated with an increased risk for breast cancer with a summary RR at 1.17 (5%CI ). Zuccolo s 12 study containing 30 and 27 case-control studies from nine UK cities reported that height was positively associated with prostate cancer (random-effects RR per 10 cm: 1.06; 5%CI ). Leo J. Schouten s 13 study containing twelve prospective studies from North America and Europe showed that height was associated with an increased ovarian cancer risk, and women with height 1.70 m had a pooled multivariate RR of 1.3 (5%CI ) compared to those with height <1.60 m. Aune s 10 study containing twelve studies (seven from Europe, four from North American and one from South Korea) showed that larger height was associated with increased risk for pancreatic cancer with a summary RR per 5-cm increase in height at 1.07 (5%CI ). The findings in our meta-analysis show an obvious association between height and risk of thyroid cancer in both men and women, which adds new evidence for the relationship between height and cancer risk. The biological mechanisms underlying the effects of height on thyroid carcinogenesis remain unknown at this stage. The insulin-like growth factor-1 (IGF-1) system might be a plausible mechanism for the association between height and thyroid cancer. The findings from Schmidt et al. s study 23 showed that IGF-1 concentration was associated with risk of thyroid carcinoma, in which a positive association between IGF-1 concentration and risk of differentiated thyroid carcinoma was reported, with an odds ratio for a doubling in IGF-1 concentration at 1.4 (5% confidence interval: ).[AQ4] The IGF-1 can influence height and plays an important role in the regulation of postnatal growth, and taller people have higher levels of IGF-1 in childhood and adolescence, which may result in increased risk of thyroid cancer. IGF-1 levels in adulthood can be influenced by food and energy intake in early childhood. 24 Higher IGF-1 levels promote mutation in various cell lines including thyroid cells. 20,24 On the other hand, the IGFs may contribute to cancer risk by stimulating cell proliferation, adhesion and migration, and inhibiting apoptosis. 20,24 Our meta-analysis also had some limitations. In this study, only two studies focused on the association between

6 Jing et al. 14 Figure 2. Forest plot showing the risk of thyroid cancer per 5-cm increase in height. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.] height and DTC, while the other nine studies focused on all types of thyroid cancer without differentiating thyroid cancer histology. We performed a subgroup analysis by thyroid cancer pathology classification and found that risk of thyroid cancer was increased in both DTC and all types of thyroid cancer. Future studies are needed to further assess the relationship between height and different types of thyroid cancer by histology. In addition, none of the selected studies examined the effects of height on prognosis of thyroid cancer. As a result, we were unable to explore the relationship between height and prognosis of thyroid cancer. Finally, this metaanalysis had regional restrictions, as most of the included studies were from the western countries. More prospective studies with well-design from Asian and African countries would be helpful to examine the validity our findings in a broader scope. In conclusion, the results from this meta-analysis strongly support that larger height is associated with an increased risk of thyroid cancer in both men and women. Acknowledgements We thank the authors for providing the data included the study. References 1. Schneider DF, Chen H. New developments in the diagnosis and treatment of thyroid cancer. CA Cancer J Clin 2013;63: Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin 2011;61: Vigneri R, Malandrino P, Vigneri P. The changing epidemiology of thyroid cancer: why is incidence increasing? Curr Opin Oncol 2015;27: Landa I, Robledo M. Association studies in thyroid cancer susceptibility: are we on the right track? J Mol Endocrinol 2011;47:R Adjadj E, Schlumberger M, de Vathaire F. Germline DNA polymorphisms and susceptibility to differentiated thyroid cancer. Lancet Oncol 200; 10: Yeo Y, Ma SH, Hwang Y, et al. Diabetes mellitus and risk of thyroid cancer: a meta-analysis. PLoS One 2014;:e Engeland A, Tretli S, Akslen LA, et al. Body size and thyroid cancer in two million Norwegian men and women. Br J Cancer 2006;5: Kitahara CM, Platz EA, Freeman LE, et al. Obesity and thyroid cancer risk among U.S. men and women: a pooled analysis of five prospective studies. Cancer Epidemiol Biomarkers Prev 2011; 20: Rinaldi S, Lise M, Clavel-Chapelon F, et al. Body size and risk of differentiated thyroid carcinomas: findings from the EPIC study. Int J Cancer 2012; 131:E Aune D, Vieira AR, Chan DS, et al. Height and pancreatic cancer risk: a systematic review and meta-analysis of studies. Cancer Causes Control 2012;23: Green J, Cairns BJ, Casabonne D, et al. Height and cancer incidence in the million women study: prospective, and meta-analysis of prospective studies of height and total cancer risk. Lancet Oncol 2011;12: Zuccolo L, Harris R, Gunnell D, et al. Height and prostate cancer risk: a large nested case-control study (ProtecT) and meta-analysis. Cancer. Epidemiol Biomarkers Prev 200;17: Schouten LJ, Rivera C, Hunter DJ, et al. Height, body mass index, and ovarian cancer: a pooled analysis of 12 studies. Cancer. Epidemiol Biomarkers Prev 200;17:02 12.

7 140 Height and thyroid cancer 14. Iribarren C, Haselkorn T, Tekawa IS, et al. Cohort study of thyroid cancer in a San Francisco bay area population. Int J Cancer 2001;3: Sung J, Song YM, Lawlor DA, et al. Height and site-specific cancer risk: a study of a Korean adult population. Am J Epidemiol 200; 170: Clavel-Chapelon F, Guillas G, Tondeur L, et al. Risk of differentiated thyroid cancer in relation to adult weight, height and body shape over life: the French E3N. Int J Cancer 2010; 126: Meinhold CL, Ron E, Schonfeld SJ, et al. Nonradiation risk factors for thyroid cancer in the US radiologic technologists study. Am J Epidemiol 2010;171: Kabat GC, Kim MY, Thomson CA, et al. Anthropometric factors and physical activity and risk of thyroid cancer in postmenopausal women. Cancer Causes Control 2012;23: Kabat GC, Heo M, Kamensky V, et al. Adult height in relation to risk of cancer in a of Canadian women. Int J Cancer 2013;132: Farfel A, Kark JD, Derazne E, et al. Predictors for thyroid carcinoma in Israel: a national of 1,624,310 adolescents followed for up to 40 years. Thyroid 2014;24: Kitahara CM, Gamborg M, Berrington de Gonzalez A, et al. Childhood height and body mass index were associated with risk of adult thyroid cancer in a large study. Cancer Res 2014;74: Wells GA, Shea B, O connell D, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomized studies in meta-analyses. Ottawa, Canada: Ottawa Health Research Institute, Schmidt JA, Allen NE, Almquist M, et al. Insulin-like growth factor-i and risk of differentiated thyroid carcinoma in the European prospective investigation into cancer and nutrition. Cancer Epidemiol Biomarkers Prev 2014;23: Ben-Shlomo Y, Holly J, McCarthy A, et al. Prenatal and postnatal milk supplementation and adult insulin-like growth factor I: long-term follow-up of a randomized controlled trial. Cancer Epidemiol Biomarkers Prev 2005; 14:1336.