- Research article
- Open Access
- Open Peer Review
Time trends and age-period-cohort analyses on incidence rates of thyroid cancer in Shanghai and Hong Kong
© Xie et al.; licensee BioMed Central. 2014
- Received: 4 November 2014
- Accepted: 11 December 2014
- Published: 18 December 2014
Increasing incidence rates of thyroid cancer have been noted worldwide, while the underlying reasons remain unclear.
Using data from population-based cancer registries, we examined the time trends of thyroid cancer incidence in two largest cities in China, Shanghai and Hong Kong, during the periods 1973–2009 and 1983–2011, respectively. We further performed age-period-cohort analyses to address the possible underlying reasons for the observed temporal trends.
We observed continuous increases in the incidence rates of thyroid cancer in Shanghai and Hong Kong, since the 1980s, in addition to higher incidence rates in the 1970s in both sexes in Shanghai. The age-standardized incidence rate of thyroid cancer increased by 3.1% [95% confidence interval (CI): 1.0%, 5.1%] and 3.8% (95% CI: 1.9%, 5.7%) per year on average, respectively, in Shanghai men and women during the period 1973–2009, while it increased by 2.2% (95% CI: 1.5%, 2.8%) and 2.7% (1.6%, 3.8%) per year on average, respectively, in Hong Kong men and women during the period 1983–2011. We observed global changes in trends across all age groups in similar ways, in addition to varied trends across different generations (birth cohorts).
The increased incidence rates of thyroid cancer in these two Chinese populations during recent decades may be contributable to a combination of the introduction of more sensitive diagnostic techniques and the increasing prevalence of environmental exposures in the populations.
- Thyroid cancer
- Time trend
- Age–period–cohort analysis
Thyroid cancer is a malignancy that arises from follicular or parafollicular thyroid cells. A steady increase in the incidence rate of thyroid cancer has been noted in recent decades all over the world, especially in women [1–5]. Previous studies also reported a noteworthy increase in the incidence rate of thyroid cancer in Chinese populations [6–8]. A upward trend was suggested in Hong Kong women, jumping from the 12th in 1999 to 5th most common cancer in 2011 . The increasing incidence rates were indicated by the annual percentage change (APC) of 14.4% and 19.9% in men and women, respectively, in Shanghai since the early 2000s .
One possible explanation for the observed increase in the incidence rate of thyroid cancer may be the more frequent use of sensitive diagnostic procedures, such as ultrasound, Doppler examination, CT and MRI scanning, and biochemical markers, during recent decades, which may have increased the detection of thyroid cancers [10, 11]. On the hand, it is also possible attributable to the increasing prevalence of environmental risk factors for thyroid cancer in the population, which was supported by the fact that the increase of thyroid cancer incidence was not restricted to small tumors only [1, 12]. Overall, the underlying causes for the worldwide increase in thyroid cancer incidence remain unclear and are most likely to be multifactorial.
Age-period-cohort analysis is a helpful tool for interpretation of observed temporal trends in disease rates over time, which attempts to sort out the effects of age, calendar period, and birth cohort on disease rates by fitting statistical regression models. Changes in observed disease rate over time in vital registries may be affected by artifacts that alter the estimates of disease rates, such as changes in definition of diseases, improved completeness and quality of reporting systems, and utilization of more frequent and sensitive diagnostic techniques, which may not necessarily indicate true underlying disease burden. In such cases, we would observe a global change in trends that affects the rates across all age groups in a similar way, which is referred to as “period effect”. Temporal changes in disease rates associated with environmental and biological risk factors usually vary across different generations (birth cohorts) being exposed to different exposures, and are known as “cohort effect” [13, 14].
To better understand the temporal trends in the incidence rates of thyroid cancer and the underlying reasons, we examined the time trends of thyroid cancer incidence in two largest cities in China, Shanghai and Hong Kong, during the periods 1973–2009 and 1983–2011, respectively. We further performed age-period-cohort analyses to address the effects of birth cohort and calendar period on the observed temporal trends using a newly developed statistical web tool . Etiological implications were also considered with reference to possible environmental risk factors.
We obtained the age- and sex- specific data on all newly diagnosed thyroid cancer cases in Shanghai during 1973–2009 and in Hong Kong during 1983–2011 from Shanghai Cancer Registry and Hong Kong Cancer Registry, respectively. Cancer incidence data from these two population-based cancer registries have been included in the Cancer Incidence in Five Continents series since the 1970s. Age- and sex-specific population data were from Shanghai Municipal Public Security Bureau and the Hong Kong government Census and Statistics Department, respectively.
Age-standardized annual incidence rates were calculated by the direct method using the WHO World Standard Population (1966) as the reference. We used Joinpoint Regression Program developed by US National Cancer Institute (NCI) which identified changing points of the trend and estimate the Annual Percentage Change (APC), under the assumption that the rate changed at a constant percentage every year change linearly on a log scale, for each time segment. The Average Annual Percent Change (AAPC), a weighted average of APCs from the joinpint models with weights equal to the length of the APC interval, was also computed as a summary measure of the trend over the whole observation period .
We further performed age-period-cohort regression for each gender to examine the age, period and cohort effects the on incidence rates of thyroid cancer using a web tool for age-period-cohort analysis, which was newly developed by the US NCI . This online web tool can provide the longitudinal age curve in the disease rates which is a smoothing summary curve from observed cohort-specific age-specific rates and considered as superior to age-specific rates derived from cross-sectional data for understanding the age pattern of disease risk. The APCs for each age group, called “local drifts”, can be generated from log-linear regressions. The web tool can also calculate the relative rate in any given calendar period (or birth cohort) versus a referent period (or birth cohort), adjusted for age and non-linear cohort (or period) effects. The central age group, period, and birth cohort were defined as the reference, respectively, in all age-period-cohort analyses. In case of an even number of categories, the reference value was set as the lower of the two central values. Since we only have access to incidence data by 5-year age groups, were used the same 5-year intervals for calendar periods and birth cohorts, so the age-period-cohort analyses were only performed in periods of multiplies of 5, during 1973–2007 in Shanghai and during 1987–2011 in Hong Kong, respectively.
This study was performed with the approval from the Ethics Committee of Shenzhen Center for Disease Prevention and Control and in compliance with the Helsinki Declaration. No information to identify individual subjects was included in the study.
Time trends of age-standardized incidence rates
APC (95% CI)
17.1 (−0.6, 38.0)
−16.7 (−22.6, −10.3)*
2.9 (1.8, 4.1)*
14.0 (10.7, 17.5)*
AAPC (95% CI) = 3.1 (1.0, 5.1) *
16.9 (−10.8, 53.1)
−13.2 (−16.3, −10.0)*
5.3 (4.4, 6.2)*
18.4 (14.2, 22.7)*
AAPC (95% CI) = 3.8 (1.9, 5.7) *
Hong Kong, men
2.2 (1.5, 2.8)*
AAPC (95% CI) = 2.2 (1.5, 2.8) *
Hong Kong, women
6.8 (2.6, 11.2)*
−0.1 (−1.0, 0.9)
4.6 (2.9, 6.4)*
AAPC (95% CI) = 2.7 (1.6, 3.8) *
Wald tests suggested statistically significant cohort and period effects for both populations (P < 0.05 for all). The local drifts were statistically significant for both sexes in Hong Kong (P < 0.05 for both) but not significant in Shanghai (P = 0.376 for men, and P = 0.126 for women).
A worldwide upwards trend in the incidence rate of thyroid cancer has been documented in recent decades. In this study, we have described continuous increase in the incidence rate of thyroid cancer since early 1980s in two Chinese populations, in Shanghai and Hong Kong. We also observed relatively higher incidence rate during the period of early 1970s to early 1980s in both sexes in Shanghai. The increased incidence rate across populations in certain periods may be, at least partially, explained by the use of sensitive diagnostic procedures, such as the introduction of ultrasound examination in the 1970s in China and more sensitive imaging techniques (e.g. CT, MRI and PET scan) in recent years. Such speculations were also supported by the observed period effects in the age-period-cohort analyses. The increasing incidence rate would be more likely to be explained by period effects in Shanghai, given the similar changes across age groups as indicated by non-significant local drift values. On the other hand, the increasing thyroid cancer incidence may also suggest a true increase in the risk of thyroid cancer in the populations, as the magnitude of changes over time varied across age groups and the estimated cohort effects increased for recent birth cohorts.
The etiology of thyroid cancer has not been completely understood till now, whereas ionizing radiation exposure is the only unequivocally established environmental risk factor for thyroid cancer [17, 18]. A continuous increase in the frequency of medical diagnostic and therapeutic nuclear medicine procedures in Shanghai has been described during the 12 years before 2008, and the annual individual radiation dose due to medical procedures had doubled . A survey by Hong Kong Census and Statistic Department in 2008 found that around 17% of the population aged 15 years and above had medical checkup regularly, among which 68% had medical checkups taken once every 7 to 12 months and one third of the checkups included X-rays . More frequent use of nuclear medical procedures may have resulted in increased exposures to radiation, and thus, have contributed to the increased incidence of thyroid cancer.
Our study confirmed the female predominance in the incidence rate of thyroid cancer and also observed a downward inflection in the age curve of thyroid cancer risk after menopausal ages in women, which suggest a pivotal role of oestrogen in the development of thyroid cancer . Oestrogen as a risk factor for thyroid cancer was also supported by experimental studies showing that oestrogen was a potent simulator of both human benign and malignant thyroid cells [22, 23]. If such hypothesis is confirmed with further evidence, the increasing incidence of thyroid cancer would be possible to be explained, to some extent, by the exposure to endocrine disrupting chemicals (EDCs) in the population [24, 25].
Epidemiological evidence concerning iodine intake and thyroid cancer risk remains largely lacking and controversial. Previous case–control studies reported statistically non-significant increased thyroid cancer risk associated with higher dietary intake of iodine [26, 27], while inverse associations between dietary iodine intake and thyroid cancer risk were observed in others [28, 29]. China introduced universal salt iodization in 1995 to reduce the prevalence of iodine deficiency in Mainland China , while no iodine supplementation program was implemented in Hong Kong. We observed a sharp increasing in thyroid cancer incidence in Shanghai since the early 2000s, around 5–7 years after the implementation of the universal salt iodination, but there was no commensurate marked increase in cohort effects in the age-period-cohort analysis. Thus, our results did not reveal a clear association between the salt iodination program and thyroid cancer risk in the population in Shanghai, which still needs to be clarified in analytic epidemiological studies.
Previous studies have indicated a higher risk of thyroid cancer in individuals with a higher socioeconomic status [31, 32]. Such observations may be explained by the increased medical radiation exposure and diet with more energy intake, which may in turn, lead to elevated body mass and consequently increased risk of thyroid cancer . Our findings suggested those born after mid-1945s had increased risk of thyroid cancer, which might be linked to the improved living conditions and nutrition in the populations after the World War II. The increasing incidence rates of thyroid cancer may also be attributable to the increasing prevalence of other potential risk factors, particularly exposures to environmental carcinogens, in the populations during recent decades. The candidate exposures may include, but not restricted to, EDCs, nitrite and nitrate ingested through drinking water, solvents, and metals [18, 34]. Nevertheless, confirmation of the possible causal relationships between environmental pollutants and thyroid cancer still warrants more epidemiological investigations in the future.
Since different histological types of thyroid cancer may not be necessarily etiologically homogenous, the changing epidemiology of thyroid cancer may have varied across histological types due to the possible distinct temporal trends in the prevalence of specific risk factors in the populations. Reports from other populations have indicated that the increasing incidence rate of thyroid cancer was mostly in that of papillary thyroid cancer [35, 36]. However, we were not able to perform sub-group analyses on the time trends in the incidence rate of thyroid cancer due to lack of information on histological types, which would be a major limitation of this study. In addition, although we attempted to sort out the effects of birth cohorts and calendar periods on the observed trends in the incidence rates of thyroid cancer after adjustment for age, all etiological interpretations need to be understood with caution because of the inherent limitations of age-period -cohort analysis, such as collinearity among age, period and cohort effects. Furthermore, all time trends analyses on disease rates in this study were ecological descriptive analyses at population levels without inference at individual levels. This study was inevitably subject to ecological fallacy, since interpretations from results at population levels do not necessarily hold for individuals. Therefore, all hypotheses raised in this study still need further confirmation in analytic epidemiological studies.
In summary, we observed continuous increases in the incidence rates of thyroid cancer in two Chinese populations, in Shanghai and Hong Kong, since the 1980s, in addition to higher incidence rates in the 1970s in both sexes in Shanghai. The increased incidence rates of thyroid cancer in these two Chinese populations during recent decades may be contributable to a combination of the introduction of more sensitive diagnostic techniques and the increasing prevalence of environmental exposures in the populations. More analytic epidemiological studies are warranted to clarify the underlying reasons for the increasing incidence rate of thyroid cancer and the causes of thyroid cancer.
We thank Dr. Fan Wu and colleagues from Shanghai Municipal Center for Disease Prevention and Control for providing data from Shanghai Cancer Registry.
- Enewold L, Zhu K, Ron E, Marrogi AJ, Stojadinovic A, Peoples GE, Devesa SS: Rising thyroid cancer incidence in the United States by demographic and tumor characteristics, 1980–2005. Cancer Epidemiol Biomarkers Prev. 2009, 18: 784-791. 10.1158/1055-9965.EPI-08-0960.View ArticlePubMedPubMed CentralGoogle Scholar
- Finlayson A, Barnes I, Sayeed S, McIver B, Beral V, Ali R: Incidence of thyroid cancer in England by ethnic group, 2001–2007. Br J Cancer. 2014, 110: 1322-1327. 10.1038/bjc.2014.4.View ArticlePubMedPubMed CentralGoogle Scholar
- La Vecchia C, Malvezzi M, Bosetti C, Garavello W, Bertuccio P, Levi F, Negri E: Thyroid cancer mortality and incidence: A global overview. Int J Cancer. 2014, [Epub ahead of print] doi:10.1002/ijc.29251Google Scholar
- Pellegriti G, Frasca F, Regalbuto C, Squatrito S, Vigneri R: Worldwide increasing incidence of thyroid cancer: update on epidemiology and risk factors. J Cancer Epidemiol. 2013, 2013: 965212-View ArticlePubMedPubMed CentralGoogle Scholar
- Vigneri R, Malandrino P, Vigneri P: The changing epidemiology of thyroid cancer: why is incidence increasing?. Curr Opin Oncol. 2014, [Epub ahead of print] doi:10.1097/CCO.0000000000000148Google Scholar
- Wang Y, Wang W: Increasing incidence of thyroid cancer in Shanghai, China, 1983-2007. Asia Pac J Public Health. 2012, [Epub ahead of print] doi:10.1177/1010539512436874Google Scholar
- Du LB, Li HZ, Wang XH, Zhu C, Liu QM, Li QL, Li XQ, Shen YZ, Zhang XP, Ying JW, Yu CD, Mao WM: Analysis of cancer incidence in Zhejiang cancer registry in China during 2000 to 2009. Asian Pac J Cancer Prev. 2014, 15: 5839-5843. 10.7314/APJCP.2014.15.14.5839.View ArticlePubMedGoogle Scholar
- Xie WC, Chan MH, Mak KC, Chan WT, He M: Trends in the incidence of 15 common cancers in Hong Kong, 1983–2008. Asian Pac J Cancer Prev. 2012, 13: 3911-3916. 10.7314/APJCP.2012.13.8.3911.View ArticlePubMedGoogle Scholar
- Hong Kong Cancer Registry: Cancer Statistics Query System (CanSQS). Book Cancer Statistics Query System (CanSQS). City: Hong Kong Cancer Registry, Available at http://www3.ha.org.hk/cancereg/e_a1b.asp [Accessed on Oct 20 2014],
- Li N, Du XL, Reitzel LR, Xu L, Sturgis EM: Impact of enhanced detection on the increase in thyroid cancer incidence in the United States: review of incidence trends by socioeconomic status within the surveillance, epidemiology, and end results registry, 1980–2008. Thyroid. 2013, 23: 103-110. 10.1089/thy.2012.0392.View ArticlePubMedPubMed CentralGoogle Scholar
- Wartofsky L: Increasing world incidence of thyroid cancer: increased detection or higher radiation exposure?. Hormones (Athens). 2010, 9: 103-108. 10.14310/horm.2002.1260.View ArticleGoogle Scholar
- Rego-Iraeta A, Perez-Mendez LF, Mantinan B, Garcia-Mayor RV: Time trends for thyroid cancer in northwestern Spain: true rise in the incidence of micro and larger forms of papillary thyroid carcinoma. Thyroid. 2009, 19: 333-340. 10.1089/thy.2008.0210.View ArticlePubMedGoogle Scholar
- Rosenberg PS, Anderson WF: Age-period-cohort models in cancer surveillance research: ready for prime time?. Cancer Epidemiol Biomarkers Prev. 2011, 20: 1263-1268. 10.1158/1055-9965.EPI-11-0421.View ArticlePubMedPubMed CentralGoogle Scholar
- Robertson C, Boyle P: Age-period-cohort analysis of chronic disease rates. I: Modelling approach. Stat Med. 1998, 17: 1305-1323. 10.1002/(SICI)1097-0258(19980630)17:12<1305::AID-SIM853>3.0.CO;2-W.View ArticlePubMedGoogle Scholar
- Rosenberg PS, Check DP, Anderson WF: A web tool for age-period-cohort analysis of cancer incidence and mortality rates. Cancer Epidemiol Biomarkers Prev. 2014, [Epub ahead of print] doi:10.1158/1055-9965.EPI-1114-0300Google Scholar
- Kim HJ, Fay MP, Feuer EJ, Midthune DN: Permutation tests for joinpoint regression with applications to cancer rates. Stat Med. 2000, 19: 335-351. 10.1002/(SICI)1097-0258(20000215)19:3<335::AID-SIM336>3.0.CO;2-Z.View ArticlePubMedGoogle Scholar
- Dal Maso L, Bosetti C, La Vecchia C, Franceschi S: Risk factors for thyroid cancer: an epidemiological review focused on nutritional factors. Cancer Causes Control. 2009, 20: 75-86. 10.1007/s10552-008-9219-5.View ArticlePubMedGoogle Scholar
- Marcello MA, Malandrino P, Almeida JF, Martins MB, Cunha LL, Bufalo NE, Pellegriti G, Ward LS: The influence of the environment on the development of thyroid tumors: a new appraisal. Endocr Relat Cancer. 2014, 21: T235-T254. 10.1530/ERC-14-0131.View ArticlePubMedGoogle Scholar
- Yi Y, Zheng J, Zhuo W, Gao L: Trends in radiation exposure from clinical nuclear medicine procedures in Shanghai, China. Nucl Med Commun. 2012, 33: 331-336. 10.1097/MNM.0b013e32834f2a28.View ArticlePubMedGoogle Scholar
- HKCSD: Thematic Household Survey Report No. 41. Knowledge, Attitude and Practice of Medical Checkup. Book Thematic Household Survey Report No. 41. Knowledge, Attitude and Practice of Medical Checkup. 2009, City: Hong Kong Census and Statistics Department, 160-185.Google Scholar
- Derwahl M, Nicula D: Estrogen and its role in thyroid cancer. Endocr Relat Cancer. 2014, 21: T273-T283. 10.1530/ERC-14-0053.View ArticlePubMedGoogle Scholar
- Manole D, Schildknecht B, Gosnell B, Adams E, Derwahl M: Estrogen promotes growth of human thyroid tumor cells by different molecular mechanisms. J Clin Endocrinol Metab. 2001, 86: 1072-1077.PubMedGoogle Scholar
- Zeng Q, Chen GG, Vlantis AC, van Hasselt CA: Oestrogen mediates the growth of human thyroid carcinoma cells via an oestrogen receptor-ERK pathway. Cell Prolif. 2007, 40: 921-935. 10.1111/j.1365-2184.2007.00471.x.View ArticlePubMedGoogle Scholar
- Li LX, Chen L, Meng XZ, Chen BH, Chen SQ, Zhao Y, Zhao LF, Liang Y, Zhang YH: Exposure levels of environmental endocrine disruptors in mother-newborn pairs in China and their placental transfer characteristics. PLoS One. 2013, 8: e62526-10.1371/journal.pone.0062526.View ArticlePubMedPubMed CentralGoogle Scholar
- Wan HT, Leung PY, Zhao YG, Wei X, Wong MH, Wong CK: Blood plasma concentrations of endocrine disrupting chemicals in Hong Kong populations. J Hazard Mater. 2013, 261: 763-769.View ArticlePubMedGoogle Scholar
- Truong T, Baron-Dubourdieu D, Rougier Y, Guenel P: Role of dietary iodine and cruciferous vegetables in thyroid cancer: a countrywide case–control study in New Caledonia. Cancer Causes Control. 2010, 21: 1183-1192. 10.1007/s10552-010-9545-2.View ArticlePubMedPubMed CentralGoogle Scholar
- Kolonel LN, Hankin JH, Wilkens LR, Fukunaga FH, Hinds MW: An epidemiologic study of thyroid cancer in Hawaii. Cancer Causes Control. 1990, 1: 223-234. 10.1007/BF00117474.View ArticlePubMedGoogle Scholar
- Horn-Ross PL, Morris JS, Lee M, West DW, Whittemore AS, McDougall IR, Nowels K, Stewart SL, Spate VL, Shiau AC, Krone MR: Iodine and thyroid cancer risk among women in a multiethnic population: the Bay Area Thyroid Cancer Study. Cancer Epidemiol Biomarkers Prev. 2001, 10: 979-985.PubMedGoogle Scholar
- Clero E, Doyon F, Chungue V, Rachedi F, Boissin JL, Sebbag J, Shan L, Bost-Bezeaud F, Petitdidier P, Dewailly E, Rubino C, de Vathaire F: Dietary iodine and thyroid cancer risk in French Polynesia: a case–control study. Thyroid. 2012, 22: 422-429. 10.1089/thy.2011.0173.View ArticlePubMedGoogle Scholar
- Wu Y, Li X, Chang S, Liu L, Zou S, Hipgrave DB: Variable iodine intake persists in the context of universal salt iodization in China. J Nutr. 2012, 142: 1728-1734. 10.3945/jn.112.157982.View ArticlePubMedPubMed CentralGoogle Scholar
- Choi SW, Ryu SY, Han MA, Park J: The association between the socioeconomic status and thyroid cancer prevalence; based on the Korean National Health and Nutrition Examination Survey 2010–2011. J Korean Med Sci. 2013, 28: 1734-1740. 10.3346/jkms.2013.28.12.1734.View ArticlePubMedPubMed CentralGoogle Scholar
- Sprague BL, Warren Andersen S, Trentham-Dietz A: Thyroid cancer incidence and socioeconomic indicators of health care access. Cancer Causes Control. 2008, 19: 585-593. 10.1007/s10552-008-9122-0.View ArticlePubMedGoogle Scholar
- Marcello MA, Cunha LL, Batista FA, Ward LS: Obesity and thyroid cancer. Endocr Relat Cancer. 2014, 21: T255-T271. 10.1530/ERC-14-0070.View ArticlePubMedGoogle Scholar
- Miller MD, Crofton KM, Rice DC, Zoeller RT: Thyroid-disrupting chemicals: interpreting upstream biomarkers of adverse outcomes. Environ Health Perspect. 2009, 117: 1033-1041. 10.1289/ehp.0800247.View ArticlePubMedPubMed CentralGoogle Scholar
- Davies L, Welch HG: Increasing incidence of thyroid cancer in the United States, 1973–2002. JAMA. 2006, 295: 2164-2167. 10.1001/jama.295.18.2164.View ArticlePubMedGoogle Scholar
- Aschebrook-Kilfoy B, Ward MH, Sabra MM, Devesa SS: Thyroid cancer incidence patterns in the United States by histologic type, 1992–2006. Thyroid. 2011, 21: 125-134. 10.1089/thy.2010.0021.View ArticlePubMedPubMed CentralGoogle Scholar
- The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/14/975/prepub
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.