Increased Risk Of Thyroid Cancer Research Articles

Association of XRCC1 polymorphisms with thyroid cancer risk

Due to the important role in the DNA repair pathways, numerous studies have been carried out to explore the relationship between the polymorphisms in the X-ray repair cross-complementing group 1 (XRCC1) gene and thyroid cancer risk. But previous reports have produced conflicting results. Thus, we performed an updated comprehensive meta-analysis to better investigate the association of the XRCC1 polymorphisms with thyroid cancer risk. There were a total of nine studies included with 1,621 cases and 3,669 controls examining the effects of the XRCC1 Arg280His, Arg399Gln, and Arg194Trp polymorphisms on the susceptibility of thyroid cancer. In our study, the XRCC1 Arg280His polymorphism was found to be associated with an increased thyroid cancer risk in the Caucasian population [allelic contrast: odds ratio (OR) = 1.38, 95% CI = 1.05-1.80, P(Z) = 0.02, P(Q) = 0.61; dominant model: OR = 1.43, 95% CI = 1.08-1.89, P(Z) = 0.01, P(Q) = 0.57]. The Arg399Gln polymorphism was associated with a significant decreased risk [allelic contrast: OR = 0.73, 95% CI = 0.59-0.92, P(Z) = 0.006, P(Q) = 0.31; dominant model: OR = 0.73, 95% CI = 0.55-0.97, P(Z) = 0.03, P(Q) = 0.33; recessive model: OR = 0.56, 95% CI = 0.34-0.93, P(Z) = 0.02, P(Q) = 0.59], while the Arg194Trp SNP conferred an increased risk for thyroid cancer in the mixed populations [allelic contrast: OR = 1.49, 95% CI = 1.02-2.17, P(Z) = 0.04]. To conclude, the present meta-analysis demonstrated that the polymorphisms in the XRCC1 gene may be associated with developing of thyroid cancer.

Obesity and Thyroid Cancer: A Clinical Update

In the last decade, significant contributions have been made to our knowledge on the connection between the thyroid and adipose tissue. Modern society is faced with climbing rates of obesity and metabolic syndrome, and there is accumulating evidence of an association between obesity and increased cancer risk. The aim of this review is to summarize clinical data on the association between thyroid cancer (TC) and obesity and briefly to present plausible hypotheses explaining this interplay. We performed a search on the PubMed database for studies published in English from 1980 to March 2013 using the terms "thyroid cancer," "obesity," and "body mass index." Although there is inconsistency among the clinical studies, it seems that overweight and obesity are related to a modestly increased TC risk. Various factors, such as sex, ethnicity, and body changes during certain life periods, for example adolescence, may influence the association between obesity and TC risk. There are preliminary data linking obesity with a less favorable clinicopathologic profile of TC. However, validation with larger multicenter studies is needed. The precise underlying mechanisms have not yet been elucidated, but the insulin-IGF axis and adipokines, such as leptin and adiponectin, might be implicated in the link between excess weight and TC. Given the rising prevalence of TC and the development of obesity as an epidemic, it is important to clarify its connection with TC as well as the mediating pathways. However, unless this association is confirmed and causation proven, screening for TC in overweight and obese subjects-a rapidly increasing body of the general population-does not seem justified.

Obesity and Thyroid Cancer: Is Leptin the (Only) Link?

Obesity and Thyroid Cancer: Is Leptin the (Only) Link?

Increased thyroid cancer risk in acromegaly

Acromegaly increases cancer risk. We aimed to determine the prevalence and the predictors of tumors in acromegalic patients treated at our department. We retrospectively evaluated 160 acromegalic patients [79 female (mean age 52.0 ± 10.4 years) and 81 male (mean age 49.1 ± 12.4 years)] between 1990 and 2012, with a mean follow up period of 7.1 ± 5.7 years. The patients were screened with colonoscopy, mammography, thyroid and prostate ultrasonography. Malignancy was found in 34 (21.3%) patients. No significant difference was observed in the distribution of malignancy among sexes (20.3% in F vs. 22.2% in M). Thyroid cancer was the most frequent (n = 17, 10.6%) followed by the breast cancer (n = 4, 2.5%) and colorectal cancer (n = 3, 1.8%). Renal cell cancer in two patients, bladder cancer in two patients, periampullary tumor, rectal carcinoid tumor, malignant melanoma, prostate cancer, lung cancer, parotid mucoepidermoid carcinoma and malignant mesenchymal tumor in brain in one patient were detected. One patient had both thyroid and renal cell cancer. Age of patients at diagnosis of acromegaly was significantly higher in patients with cancer (45.8 ± 9.9 vs. 40.9 ± 11.3 years, p < 0.05). No significant difference was found in duration of the disease, initial GH levels and IGF-1% upper limit of normal values, the prevalence of diabetes, hypertension, coronary heart disease, hyperlipidemia and treatment modalities between the patients with/without cancer. In logistic regression analysis, older age at diagnosis was associated with malignancy risk. The risk of cancer in acromegaly especially the thyroid cancer risk seems to be more increased than known in the literature. Therefore, acromegaly patients should be screened routinely for cancer, especially for thyroid cancer due to it being up to four times higher prevalence than breast and colorectal cancer.

Increased thyroid cancer risk in acromegaly

Acromegaly increases cancer risk. We aimed to determine the prevalence and the predictors of tumors in acromegalic patients treated at our department. We retrospectively evaluated 160 acromegalic patients [79 female (mean age 52.0 ± 10.4 years) and 81 male (mean age 49.1 ± 12.4 years)] between 1990 and 2012, with a mean follow up period of 7.1 ± 5.7 years. The patients were screened with colonoscopy, mammography, thyroid and prostate ultrasonography. Malignancy was found in 34 (21.3 %) patients. No significant difference was observed in the distribution of malignancy among sexes (20.3 % in F vs. 22.2 % in M). Thyroid cancer was the most frequent (n = 17, 10.6 %) followed by the breast cancer (n = 4, 2.5 %) and colorectal cancer (n = 3, 1.8 %). Renal cell cancer in two patients, bladder cancer in two patients, periampullary tumor, rectal carcinoid tumor, malignant melanoma, prostate cancer, lung cancer, parotid mucoepidermoid carcinoma and malignant mesenchymal tumor in brain in one patient were detected. One patient had both thyroid and renal cell cancer. Age of patients at diagnosis of acromegaly was significantly higher in patients with cancer (45.8 ± 9.9 vs. 40.9 ± 11.3 years, p < 0.05). No significant difference was found in duration of the disease, initial GH levels and IGF-1 % upper limit of normal values, the prevalence of diabetes, hypertension, coronary heart disease, hyperlipidemia and treatment modalities between the patients with/without cancer. In logistic regression analysis, older age at diagnosis was associated with malignancy risk. The risk of cancer in acromegaly especially the thyroid cancer risk seems to be more increased than known in the literature. Therefore, acromegaly patients should be screened routinely for cancer, especially for thyroid cancer due to it being up to four times higher prevalence than breast and colorectal cancer.

X-Ray Repair Cross-Complementing Group 1(XRCC1) Genetic Polymorphisms and Thyroid Carcinoma Risk: a Meta-Analysis

A number of studies have been conducted to explore the association of XRCC1 polymorphisms with thyroid cancer risk, but the results have been inconsistent. Thus we performed the present meta-analysis to clarify this issue based on all of the evidence available to date. Relevant studies were retrieved by searching PubMed and statistical analysis conducted using Stata software. Nine studies were included in this meta-analysis (1,620 cases and 3,557 controls). There were 6 studies (932 cases and 2,270 controls) of the Arg194Trp polymorphism, 7 studies (1432 cases and 3356 controls) of the Arg280His polymorphism and 9 studies (1,620 cases and 3,557 controls) for the Arg399Gln polymorphism. No association of XRCC1 Arg194Trp, Arg280His and Arg399Gln polymorphism with thyroid cancer risk was observed in the overall analysis. However, subgroup analysis revealed: 1) an elevated risk in aa vs AA analysis (OR=2.03, 95%CI= 1.24-3.31) and recessive genetic model analysis (OR=1.93, 95%CI= 1.20-3.08) in the larger sample size trials for XRCC1 Arg194Trp polymorphism; 2) a decreased thyroid cancer risk on subgroup analysis based on ethnicity in Aa vs AA analysis (OR=0.84, 95%CI= 0.72-0.98) and in a dominant genetic model (OR=0.84, 95%CI= 0.72-0.97) in Caucasian populations for the XRCC1 Arg399Gln polymorphism; 3) a decreased thyroid cancer risk on subgroup analysis based on design type in Aa vs AA analysis (OR=0.72, 95% CI= 0.54-0.97) among the PCC trials for the Arg399Gln polymorphism. Our results suggest that the XRCC1 Arg399Gln polymorphism may be associated with decreased thyroid cancer risk among Caucasians and XRCC1 Arg194Trp may be associated with a tendency for increased thyroid cancer risk in the two larger sample size trials.

Overweight, Obesity and Thyroid Cancer Risk: A Meta-analysis of Cohort Studies

This meta-analysis examined the relationship between excess body weight or body mass index (BMI) and risk of thyroid cancer. PubMed(®), MEDLINE(®), EMBASE™ and Academic Search™ Premier databases were searched to identify cohort studies examining the effect of being overweight or obese on the risk of thyroid cancer. The inclusion criteria were met by seven cohort studies (total number of thyroid cancer cases, 5154). The pooled relative risk (RR) of thyroid cancer was 1.13 (95% confidence interval [CI] 1.04, 1.22) for overweight. Obesity was also linked with increased thyroid cancer risk in males and females, the strength of the association increasing with increasing BMI. The combined RR of thyroid cancer was 1.18 (95% CI 1.11, 1.25) for excess body weight (overweight and obesity combined). Being overweight was associated with a significant increase in thyroid cancer risk among non-Asians, but not among Asians. Overweight, obesity and excess body weight were all associated with papillary thyroid carcinoma risk. The association between overweight/obesity/excess body weight and thyroid cancer risk was confirmed.

Common obesity-related genetic variants and papillary thyroid cancer risk.

Epidemiologic studies have shown consistent associations between obesity and increased thyroid cancer risk, but, to date, no studies have investigated the relationship between thyroid cancer risk and obesity-related single-nucleotide polymorphisms (SNP). We evaluated 575 tag SNPs in 23 obesity-related gene regions in a case-control study of 341 incident papillary thyroid cancer (PTC) cases and 444 controls of European ancestry. Logistic regression models, adjusted for attained age, year of birth, and sex were used to calculate ORs and 95% confidence intervals (CI) with SNP genotypes, coded as 0, 1, and 2 and modeled continuously to calculate P(trend). Nine of 10 top-ranking SNPs (P(trend) < 0.01) were located in the FTO (fat mass and obesity associated) gene region, whereas the other was located in INSR (insulin receptor). None of the associations were significant after correcting for multiple testing. Our data do not support an important role of obesity-related genetic polymorphisms in determining the risk of PTC. Factors other than selected genetic polymorphisms may be responsible for the observed associations between obesity and increased PTC risk.

FOXE1 polymorphisms are associated with familial and sporadic nonmedullary thyroid cancer susceptibility

FOXE1 is a transcription factor required for thyroid differentiation and function. FOXE1 locus polymorphisms (chromosome 9q22.33) were recently associated with increased sporadic thyroid cancer risk. In this study, we aimed to investigate the association of FOXE1 variants with nonmedullary thyroid cancer (NMTC), in both sporadic and familial (FNMTC) cases from the Portuguese population. Nine variants located at the FOXE1 locus were sequenced in genomic DNA from 60 FNMTC probands and 80 patients with sporadic NMTC. Alleles were tested for association with thyroid cancer, against 130 healthy matched Portuguese controls. All variants were significantly associated with increased thyroid cancer risk when combining familial and sporadic cases (OR range = 1·62-2·58). In particular, two reported risk variants were associated with the disease: rs965513 (allele A) with familial (OR = 2·30, 95% CI = 1·48-3·59, P = 0·0002) and sporadic (OR = 2·81, 95% CI = 1·87-4·22, P < 0·0001) NMTC and rs1867277 (allele A) with the sporadic (OR = 1·76, 95% CI = 1·18-2·62, P = 0·0052) and combined NMTC cases (OR = 1·70, 95% CI = 1·21-2·40, P = 0·0022). Interestingly, we also identified association of FOXE1 polyalanine tract expansions (>14 alanines) with thyroid cancer risk, in both familial (OR = 2·56, 95% CI = 1·64-4·01, P < 0·0001) and sporadic (OR = 2·44, 95% CI = 1·61-3·68, P < 0·0001) cases. We found compelling evidence of association between FOXE1 variants and thyroid cancer risk in the Portuguese population. To our knowledge, this is the first study supporting the association of this locus with both sporadic and familial NMTC susceptibility.

Thyroid cancer genetics: how close are we to personalizing clinical management?

Author for correspondence: Genomic Medicine Institute, Cleveland Clinic, 9500 Euclid Avenue, NE-50, Cleveland, OH 44195, USA and Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA and Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH 44195, USA and Thyroid Cancer Center, Endocrinology & Metabolism Institute, Cleveland Clinic, Cleveland, OH 44195, USA and Stanley Shalom Zielony Institute of Nursing Excellence, Cleveland Clinic, Cleveland, OH 44195, USA and Department of Genetics, & CASE Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA Tel.: +1 216 444 3440 Fax: +1 216 636 0655 engc@ccf.org Thyroid cancer genetics: how close are we to personalizing clinical management?

Chemotherapy and Thyroid Cancer Risk: A Report from the Childhood Cancer Survivor Study

Although ionizing radiation is an established environmental risk factor for thyroid cancer, the effect of chemotherapy drugs on thyroid cancer risk remains unclear. We evaluated the chemotherapy-related risk of thyroid cancer in childhood cancer survivors and the possible joint effects of chemotherapy and radiotherapy. The study included 12,547 five-year survivors of childhood cancer diagnosed during 1970 through 1986. Chemotherapy and radiotherapy information was obtained from medical records, and radiation dose was estimated to the thyroid gland. Cumulative incidence and relative risks were calculated with life-table methods and Poisson regression. Chemotherapy-related risks were evaluated separately by categories of radiation dose. Histologically confirmed thyroid cancer occurred in 119 patients. Thirty years after the first childhood cancer treatment, the cumulative incidence of thyroid cancer was 1.3% (95% CI, 1.0-1.6) for females and 0.6% (0.4-0.8) for males. Among patients with thyroid radiation doses of 20 Gy or less, treatment with alkylating agents was associated with a significant 2.4-fold increased risk of thyroid cancer (95% CI, 1.3-4.5; P = 0.002). Chemotherapy risks decreased as radiation dose increased, with a significant decrease for patients treated with alkylating agents (P(trend) = 0.03). No chemotherapy-related risk was evident for thyroid radiation doses more than 20 Gy. Treatments with alkylating agents increased thyroid cancer risk, but only in the radiation dose range less than 20 Gy, in which cell sparing likely predominates over cell killing. Our study adds to the evidence for chemotherapy agent-specific increased risks of thyroid cancer, which to date, were mainly thought to be related to prior radiotherapy.

Hormonal and reproductive factors and risk of postmenopausal thyroid cancer in the NIH-AARP Diet and Health Study

Background: Worldwide, thyroid cancer incidence rates are higher among women than men. While this suggests a possible etiologic role of female sex hormones, clear associations between hormonal and reproductive factors and thyroid cancer have not been observed. However, few large prospective studies have been conducted. Methods: Hazard ratios (HRs) and 95% confidence intervals (CIs) for hormonal and reproductive factors and incident thyroid cancer were estimated using Cox regression methods in the prospective US NIH-AARP Diet and Health Study. Between 1995 and 2006, 312 first primary incident thyroid cancers were diagnosed among 187,865 postmenopausal women ages 50–71 at baseline. Results: Thyroid cancer was not associated with ages at menarche or menopause, menopause type, or parity. Oral contraceptive use for ≥10 years (vs. never use) was inversely associated with thyroid cancer risk (HR, 0.48; 95%CI, 0.28–0.84; Ptrend=0.01). Women who reported current menopausal hormone therapy at baseline had an increased thyroid cancer risk vs. never users (HR 1.38; 95% CI: 1.07–1.79) but there was no trend with increasing duration of use. Women with benign breast disease (BBD) had a significantly higher thyroid cancer risk vs. women without BBD (HR, 1.47; 95% CI, 1.09–1.99). Conclusions: Our results do not support a strong role for female hormonal and reproductive factors including ages at menarche and menopause, type of menopause or parity, in thyroid cancer etiology among postmenopausal women. Compared with previous studies, no clear patterns emerge for exogenous hormone use but further analysis in large, prospective populations may be informative. The HR for BBD is consistent with the one previous prospective analysis that examined this association.

Dental X-rays may increase thyroid cancer risk

Dental X-rays may increase thyroid cancer risk

Risk of thyroid cancer after exposure to fertility drugs: results from a large Danish cohort study

Findings from the few epidemiological studies that have investigated thyroid cancer risk after fertility drugs have been inconclusive. Using data from the largest cohort of infertile women to date, we examined the effects of fertility drugs on thyroid cancer risk. A cohort of 54 362 women with infertility problems referred to Danish fertility clinics in the period 1963-1998 was established. A detailed data collection including information about type and amount of treatment was conducted. Using case-cohort techniques, we calculated rate ratios (RRs) of thyroid cancer associated with different fertility drugs after adjustment for age at first live birth. A total of 29 thyroid cancers were identified during follow-up through 2000. Use of clomiphene [RR = 2.28; 95% confidence interval (CI): 1.08-4.82] or progesterone (RR = 10.14; 95% CI: 1.93-53.33) was associated with an increased thyroid cancer risk, although the latter estimate was based on few cases. When stratifying for parity status, the risk was primarily associated with clomiphene (RR = 3.09; 95% CI: 1.21-7.88) in parous women. No significantly increased risk was found after use of gonadotrophins, hCG or GnRH. We observed no association with number of cycles of use or years since first use (latency). Clomiphene and possibly progesterone may increase thyroid cancer risk, particularly among parous women. Longer follow-up is needed to confirm our findings.

From the molecular characterization of iodide transporters to the prevention of radioactive iodide exposure

In the event of a nuclear reactor accident, the major public health risk will likely result from the release and dispersion of volatile radio-iodines. Upon body exposure and food ingestion, these radio-iodines are concentrated in the thyroid, resulting in substantial thyroidal irradiation and accordingly causing thyroid cancers. Stable potassium iodide (KI) effectively blocks thyroid iodine uptake and is thus used in iodide prophylaxis for reactor accidents. The efficiency of KI is directly related to the physiological inhibition of the thyroid function in the presence of high plasma iodide concentrations. This regulation is called the Wolff-Chaikoff effect. However, to be fully effective, KI should be administered shortly before or immediately after radioiodine exposure. If KI is provided only several hours after exposure, it will elicit the opposite effect e.g. lead to an increase in the thyroid irradiation dose. To date, clear evaluation of the benefit and the potential toxicity of KI administration remain difficult, and additional data are needed. We outline in this review the molecular characterization of KI-induced regulation of the thyroid function. Significant advances in the knowledge of the iodide transport mechanisms and thyroid physiology have been made. Recently developed molecular tools should help clarify iodide metabolism and the Wolff-Chaikoff effect. The major goals are clarifying the factors which increase thyroid cancer risk after a reactor accident and improving the KI administration protocol. These will ultimately lead to the development of novel strategies to decrease thyroid irradiation after radio-iodine exposure.

Association of Polymorphisms in ERCC2 Gene with Non-Familial Thyroid Cancer Risk

The ERCC2 protein is an evolutionary conserved ATP-dependent helicase that is associated with a TFIIH transcription factor complex and plays an important role in nucleotide excision repair. Mutations in this gene are responsible for xeroderma pigmentosum and also for Cocayne syndrome and trichothiodystrophy. Several single nucleotide polymorphisms have been identified in the ERCC2 locus. Among them, a G23591A polymorphism in the codon 312 results in an Asp --> Asn substitution in a conserved region and a A35931C polymorphism in the codon 751 results in a Lys --> Gln substitution. Because these polymorphisms have been associated with an increased risk for several types of cancers, we carried out an hospital based case-control study in a Caucasian Portuguese population to evaluate the potential role of these polymorphisms on the individual susceptibility to thyroid cancer. The results obtained did not reveal a significant association between each individual polymorphism studied (G23591A and A35931C) and an increased thyroid cancer risk, but individuals homozygous for non-wild-type variants are overrepresented in patients group. The evaluation of the different haplotypes generated by these polymorphisms showed that individuals simultaneously homozygous for rare variants of both polymorphisms have an increased risk for thyroid cancer [adjusted odds ratio (OR) 3.084; 95% confidence interval (95% CI), 1.347-7.061; P = 0.008] and for papillary thyroid-type tumors (adjusted OR, 2.997; 95% CI, 1.235-7.272; P = 0.015) but not for follicular thyroid-type tumors. These results suggest that genetic polymorphisms in this gene might be associated with individual susceptibility towards thyroid cancer, mainly papillary-type tumors, but larger studies are required to confirm these results.

Lifestyle and Other Risk Factors for Thyroid Cancer in Los Angeles County Females

PURPOSE AND METHODS: We conducted a population-based case-control study of thyroid cancer. Cases were 292 women, aged 15–54 when diagnosed between the years 1980 and 1983 (145 diagnosed in 1980–81 and 147 diagnosed in 1982–83). Female neighborhood controls ( n = 292) were matched to each case on birth-year and race. RESULTS: Among women < 35 years, thyroid disease in first-degree relatives increased thyroid cancer risk [odds ratio (OR) = 2.0, 95% confidence interval (CI) = 1.1–3.7]. Risk was not associated with fish consumption, although high childhood consumption of shellfish decreased thyroid cancer risk (OR = 0.2, 95% CI = 0.05–0.7 for consumption at least a few times weekly). Among papillary thyroid cancers (82% of cases), frequent adult consumption of saltwater fish decreased risk. Cancer risk was reduced with consumption of certain vegetables, wine, and tea. Other dietary variables, including milk, beer and hard liquor, and coffee were not related to thyroid cancer risk. Among the papillary sample, risk increased with longer use of multivitamins (OR = 2.9, 95% CI = 1.2–7.4 for > 10 years of use). Smoking and body mass were not associated with thyroid cancer risk. CONCLUSIONS: These results suggest a role of family history of thyroid disease and certain dietary variables in the etiology of thyroid cancer in adult females.

Concentration of selenium in the whole blood and the thyroid tissue of patients with various thyroid diseases.

We investigated the possible differences between the concentrations of selenium in the whole blood and thyroid tissue of patients with thyroid disease. The study comprises 41 women with nodular goiter, 19 women and 2 men with thyroid cancer, 18 women with Graves' disease, and 7 women with thyroiditis. The concentration of selenium was determined by the TRXRF method. The lowest mean selenium level was achieved in the whole blood of women with Graves' disease and the highest in the whole blood of healthy people. In the thyroid cancer tissue, we found the lowest concentration of selenium and the highest in the thyroid gland of women with nodular goiter and Graves' disease. The low selenium levels in the thyroid tissue may increase thyroid cancer risk.

A pooled analysis of case-control studies of thyroid cancer. VI. Fish and shellfish consumption.

To better understand the role of fish and shellfish on thyroid cancer risk, we systematically re-analyzed the original data from 13 case-control studies conducted in the US, Japan, China, and Europe. A total of 2497 cases (2023 women, 474 men) and 4337 controls (3268 women, 1069 men) were considered. Odds ratio (OR) and corresponding 95% confidence interval (CI) were estimated for each study by logistic regression models, conditioned on age and sex, and adjusted for history of goiter, thyroid nodules or adenomas, and radiation. Combined ORs were computed as the weighted average of the estimates from each study. The ORs for the highest level of total fish consumption (three or more times per week) as compared to the lowest one (less than once per week) was above unity in Hawaii, Connecticut, Japan, Norway, Tromsø, and Vaud. Conversely, the ORs for the studies in Los Angeles. Shanghai, southeastern Sweden, Uppsala, northern Sweden, northern Italy, and Athens were below one. The pattern of risk for salt water fish and shellfish was not substantially different from that of total fish. Fish was not associated with thyroid cancer risk in all studies combined (OR = 0.99, 95% CI 0.85-1.2 for moderate, and OR=0.88, 95% CI 0.71-1.1 for high total fish consumption), but there was a suggestion of a protective effect in endemic goiter areas (OR = 0.65, 95% CI 0.48-0.88). This combined analysis indicates that relatively elevated fish consumption does not appreciably increase thyroid cancer risk, and may have a favorable influence in areas where iodine deficiency is, or was, common.

A pooled analysis of case-control studies of thyroid cancer. III. Oral contraceptives, menopausal replacement therapy and other female hormones.

The relations between oral contraceptives (OC), hormone replacement therapy (HRT) for menopause, and other female hormone use and thyroid cancer risk was analyzed using the original data from 13 studies from North America, Asia and Europe. Based on 2,132 cases and 3,301 controls, odds ratios (OR) and the corresponding 95% confidence intervals (CI) were obtained by conditional regression models, conditioning on study and age at diagnosis, and adjusting for age, radiation exposure and parity. Overall, 808 (38%) cases versus 1,290 (39%) controls had ever used OCs, corresponding to an OR of 1.2 (95% CI 1.0 to 1.4). There was no relation with duration of use, age at first use, or use before first birth. The OR was significantly increased for current OC users (OR = 1.5, 95% 1.0 to 2.1), but declined with increasing time since stopping (OR = 1.1 for > 10 years since stopping). The association was stronger for papillary cancers (OR = 1.6 for current users) than for other histologic types. No significant heterogeneity was observed across studies or geographic areas. Eight studies had data on HRT, for a total of 1,305 cases and 2,300 controls: 110 (8%) cases and 205 (9%) controls reported ever using HRT (OR = 0.8; 95% CI 0.6 to 1.1). The ORs were 1.6 (95% to 0.9 to 2.9) for use of fertility drugs, and 1.5 (95% CI 1.1 to 2.1) for lactation suppression treatment. The studies considered in these analyses include most of the epidemiological data on the role of exogenous hormone use in the etiology of thyroid cancer, and they provide reassuring evidence on the absence of an association of practical relevance. The moderate excess risk in current OC users, if not due to increased surveillance for thyroid masses among OC users, is similar to that described for breast cancer, and would imply a role of female hormones on thyroid cancer promotion. There was no indication of increased thyroid cancer risk 10 or more years after discontinuing OC use.