Annals of Oncology Advance Access originally published online on October 19, 2007
Annals of Oncology 2008 19(2):380-383; doi:10.1093/annonc/mdm433
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epidemiology |
Glycemic index, glycemic load and thyroid cancer risk
1 Istituto di Ricerche Farmacologiche ‘Mario Negri’ Milan
2 Istituto di Statistica Medica e Biometria ‘Giulio A. Maccacaro’, Unità di Statistica Medica, Università degli Studi di Milano, Milan
3 Dipartimento di MedicinaChirurgia e Odontoiatria
4 Servizio di Epidemiologia e Biostatistica, Centro di Riferimento Oncologico, Aviano
5 Clinica Otorinolaringoiatrica, DNTB, Università Milano-Bicocca, Monza
6 Fondazione IRCCS, Istituto Nazionale Tumori, Milan, Italy
7 International Agency for Research on Cancer, Lyon, France
* Correspondence to: Dr G. Randi, Istituto di Ricerche Farmacologiche ‘Mario Negri’, Viale Eritrea 62, 20157 Milano, Italy. Tel: +39-02-39014541; Fax: +39-02-33200231; E-mail: randi{at}marionegri.it
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Abstract |
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Background: Risk of thyroid cancer has already been related to refined cereals and starch food, but the association has not been studied in terms of glycemic index (GI) and glycemic load (GL).
Patients and methods: We analyzed data from a case–control study conducted in Italy from 1986 to 1992 and including 399 histologically confirmed and incident cases of thyroid cancer and 616 control subjects. Information on dietary habits was derived through a food-frequency questionnaire and multivariate odds ratios (ORs) for GI and GL levels were estimated with adjustment for age, education, sex, area of residence, history of diabetes, body mass index, smoking, alcohol consumption, intake of fruit and vegetables, and noncarbohydrate energy intake.
Results: Compared with the lowest tertile, the ORs in subsequent tertiles were 1.68 and 1.73 for GI, and 1.76 and 2.17 for GL. The OR for highest tertile of GI compared with lowest one was 1.70 for papillary and 1.57 for follicular thyroid cancer. The ORs for GL were 2.17 for papillary and 3.33 for follicular thyroid cancer.
Conclusion: Our study shows that high dietary levels of GI and GL are associated with thyroid cancer risk.
Key words: carbohydrate intake, case–control study, glycemic index, glycemic load, risk factors, thyroid cancer
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introduction |
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TopAbstractintroductionmaterials and methodsresultsdiscussionfundingAcknowledgementsReferences |
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Thyroid cancer is a relatively rare neoplasm and, together with gall-bladder cancer, is one of the two nonsex-related cancer occurring more frequently among women than men [1]. The only well-define risk factor for thyroid cancer is ionizing radiation. History of benign thyroid diseases, iodine deficiency, and residence in endemic goiter areas are also associated with elevated risk of thyroid cancer [2]. Apart from these risk factors, the causes of thyroid cancer remain unclear.
Several aspects of diet have been related to thyroid cancer and a poor diet accounted for 
40% of cases in Italy [3]. Among the other associations found, case–control studies conducted in Italy showed increased risk for refined cereal intake [4], pasta or rice, bread, pastry, and potatoes [5], although the issue remains open to discussion [6–8].
Glycemic index (GI) and glycemic load (GL) are indicators of the physiological response to different carbohydrates in terms of plasma glucose and insulin responses [9]. High levels of GI or GL have been associated with diabetes and coronary heart diseases [10, 11], symptomatic gallstone diseases [12] and with cancer risk at several sites [10,13–19]. To our knowledge, no study has analyzed the association between GI and GL and thyroid cancer risk. We therefore addressed this issue using data from a case–control study conducted in Italy from 1986 to 1992.
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materials and methods |
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From 1986 to 1992, a case–control study on thyroid carcinoma was conducted in the major teaching and university hospitals in three areas of Northern Italy: the greater Milan area, the provinces of Pordenone, and Padua in the northeast of Italy [20]. Cases were 399 subjects (291 women and 108 men, aged 16–72 years, median age 44 years) admitted to the major teaching and general hospitals of study areas for histologically confirmed thyroid carcinoma diagnosed no >2 years before the interview. Of these, 274 had papillary carcinomas (or mixed papillary/follicular), 69 follicular, and 56 anaplastic or other undefined histological types. Control subjects were 617 patients (427 women and 190 men, aged 16–74 years, median age 46 years) admitted to the same network of hospitals as cases for acute nonneoplastic diseases unrelated to known or potential risk factors for thyroid carcinoma, and unrelated to long-term diet modification (15% traumas, 17% other nontraumatic orthopaedic diseases, 28% acute surgical conditions, and 40% other miscellaneous disorders). Controls admitted for any hormone-related disease were explicitly excluded. Cases and controls were recruited in the same catchment areas and, despite not singularly matched, they were comparable for gender and age. Less than 5% of the subjects identified (cases and controls) refused to participate.
Trained interviewers identified thyroid carcinoma cases and controls and administered to them a structured questionnaire that included questions on sociodemographic and anthropometric characteristics, lifestyle habits (including coffee and alcohol consumption), a problem-oriented medical history, family history of thyroid disease, history of residence in endemic goiter areas and number of years, use of diagnostic and therapeutic X-rays, and, for female subjects, gynecologic and reproductive history and use of exogenous hormones. The weekly frequency of consumption of 29 food items during the 2 years before the onset of symptoms that led to the diagnosis was also recorded, and food items included questions on intake of refined cereals, such as bread, pasta, rice and polenta, and consumption of fruit and vegetables. GI values were assigned to these items using international tables [21] and the average daily GI was calculated by summing the products of the carbohydrate content per serving, for each food or recipe, times the average number of servings of that food per week, times its GI, all divided by the total amount of available weekly carbohydrate intake [22]. A score for the daily average GL was computed as the GI, but without dividing by the total amount of carbohydrates. One control subject was removed from the analyses because of missing values for GI and GL. Odds ratios (ORs), and the corresponding 95% confidence intervals (CIs) for tertiles of GI and GL were computed using unconditional multiple logistic regression models [23]. We considered two models: in the first one, the regression equations included terms for age, education, sex, area of residence, history of diabetes, body mass index, smoking and alcohol consumption, and intake of fruit and vegetables. The second model included also a measure of noncarbohydrate energy intake to allow for any potential bias due to systematic over- or underreporting [24].
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results |
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Table 1 gives the distribution of 399 cases of thyroid cancer and 616 controls and the corresponding multivariate ORs of thyroid cancer according to GI and GL. Compared with the lowest tertile, the ORs in subsequent tertile values were 1.69 and 1.71 for GI and 1.82 and 2.21 for GL. After further adjustment for noncarbohydrate intake the estimates became 1.68 and 1.73 for GI and 1.76 and 2.17 for GL. Both trends in risk were significant. Continuous ORs for the difference between the 80th and 20th percentiles were 1.44 for GI and 1.70 for GL, and after further adjustment for noncarbohydrate intake the estimates were 1.47 for GI and 1.71 for GL.
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Table 2 shows the continuous effect of GI and GL on thyroid cancer risk in strata of selected variables. None of the stratification variables had a significant interaction neither with GI nor with GL.
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Table 3 shows the ORs for GL and GI according to the histological type of thyroid cancer. The OR for highest tertile of GI compared with lowest one was 1.70 for papillary and was 1.57 for follicular thyroid cancer. The ORs for GL were 2.17 for papillary and 3.33 for follicular thyroid cancer.
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discussion |
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TopAbstractintroductionmaterials and methodsresultsdiscussionfundingAcknowledgementsReferences |
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In our study, GI and GL were directly associated with risk of thyroid cancer. The GL in this group of Italian women was mainly determined by intake of bread (33.2% of total carbohydrate intake) and of pasta and rice (29.1%) and had only a minor contribution from intake of apples (6.3%) and citrus fruits (4.9%). Elevated dietary GI and GL can indicate a diet reach in refined carbohydrates (such as pasta, rice, and bread) that have been positively related to thyroid cancer risk [5], but can also indicate a less affluent diet, potentially poor in iodine and/or other nutrients associated with thyroid function [5] or a diet poor in fruit and vegetable consumption that has been inversely related to thyroid cancer risk [25, 26].
A cohort study on almost 140 000 Austrian men and women and based on 70 thyroid cancer cases found an association between baseline fasting blood glucose values and the incidence of thyroid cancer with an hazard ratio of 2.34 (95% CI : 1.15–4.78) for high levels of fasting blood glucose (6.1–6.9 mmol/l) compared with low levels (2.2–4.1 mmol/l) [27]. This supports the hypothesis that hyperglycaemia may increase the risk of thyroid cancer.
High-GI or high-GL levels increase insulin resistance. Insulin and insulin-like growth factor-I (IGF-I) have been shown to act as a cancer-promoting agent. Thyroid cell growth and function are regulated by a complex network of trophic factors (endocrine, paracrine, and autocrine factors) and thyroid-stimulating hormone (TSH) is the main growth factor for thyroid cells. Insulin/IGF-I are considered necessary cofactors for the action of TSH on follicle cells, synergizing with TSH to induce thyrocyte proliferation while maintaining differentiated function [28]. Insulin and IGF-I are not themselves mitogenic agents, but their role is described as permissive for TSH thyroid cell stimulation [29]. Furthermore, IGF-1 inhibits apoptosis, stimulates vascular endothelial growth factor (VEGF) synthesis in thyroid carcinomas [30] and high contents of VEGF messenger RNA and VEGF protein are associated with more intense mitogenic activity [31].
Due to high levels of IGF-1 found in patients with benign and malignant thyroid tumors, it has been supposed that emergent adenoma cells lose their dependence on exogenous IGF-1 and acquire the capability for autocrine production of this growth factor, resulting in continued autostimulation of cell replication, allowing thyroid nodules to become autonomous [28].
We also analyzed the association with GI and GL according to different type of thyroid cancer. Follicular thyroid cancer (17% of total number of cases) showed somewhat higher risk for high levels of GL as compared with papillary thyroid cancer (69%), although the estimates are not heterogeneous. If not due to chance, the result thus supports the hypothesis of higher effect of poor diet in the carcinogenesis of follicular than papillary thyroid cancer [3].
Estimation of average GI and GL were based on a limited number of food items and this may affect reliability and validity of the estimates. Recall bias is unlikely given that the association between food glycemic levels and thyroid cancer was not evident at the time of interviews. Hospital controls may have different dietary habits as compared with the general population. In order to avoid this bias, we excluded control subjects admitted for conditions associated with dietary modifications (diabetes mellitus, cardiovascular diseases, etc.). Moreover, the common hospital setting for cases and controls may have increased comparability of dietary history among subjects and the questionnaire was satisfactorily reproducible and reliable [32]. Participation among eligible patients was practically complete, and the catchment areas for cases and controls were comparable. With respect to confounding, adjustment for noncarbohydrate energy intake was made to control for potential over- and underreporting among cases and controls [24] and further adjustment for several potential risk and protective factors for thyroid cancer was not able to explain the association between GI and GL and thyroid cancer risk.
In conclusion, our study presents an innovative result on GI and GL association with risk of thyroid cancer, supporting the hypothesis that a diet reach in refined cereals and sugar through hyperglycemia and subsequent increase in insulin demand is related to carcinogenesis of thyroid.
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funding |
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Italian Association for Cancer Research; Italian leagues against cancer; Italian Ministry of Research (PRIN 2005).
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Acknowledgements |
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TopAbstractintroductionmaterials and methodsresultsdiscussionfundingAcknowledgementsReferences |
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The authors thank I. Garimoldi for editorial assistance.
Received for publication June 14, 2007. Accepted for publication July 26, 2007.
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References |
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