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Objective. To describe the status and results of thyroid disease screening and assessment of reliability of radiation thyroid doses in the Belarusian in utero cohort of 2,965 individuals exposed to Chernobyl (Chornobyl) fallout. Materials and methods. Thyroid screening examinations are currently underway including thyroid palpation by an endocrinologist, ultrasonographic examination by an ultrasonographer and analysis of blood samples for diagnosis of hypo- and hyperthyroidism, autoimmune thyroiditis, thyroid function tests (thyroid-stimulating hormone [TSH], thyroxine [T4], thyroid peroxidase antibody [anti-TPO], and thyroglobulin antibodies [anti-TG]). Reliability of (i) information from 780 pairs of questionnaires obtained during the first and second interviews of the mothers and (ii) thyroid doses, which were calculated for the cohort members using this information, is evaluated. Results. As of 15 August 2021, 1,267 in utero exposed study subjects had been screened. A single thyroid nodule was diagnosed in 167 persons (13.2 % of the total) and multiple thyroid nodules in 101 persons (8.0 %): 189 (14.9 %) persons had nodules detected for the first time at the screening while 79 (6.2 %) persons had nodules detected previously (pre-screening nodules). Fifty-nine out of 268 subjects (22.0 %) with a suspicious thyroid nodule were referred to fine needle aspiration biopsy, and among them 33 (55.9 %) were biopsied. Reasonable agreement was observed for model-based doses calculated for the Belarusian in utero cohort members using data from the two interviews (Spearman’s rank-correlation coefficient rs = 0.74, p < 0.001), while measurement-based doses yielded almost perfect agreement (rs = 0.99, p < 0.001). Conclusions. During the thyroid screening, at least one thyroid nodule was identified in 268 of 1,267 (21.2 %) in utero exposed cohort members. Seven thyroid cancer cases were identified in the cohort, including 5 pre-screening cases and 2 cases detected during the screening. Ongoing research on this unique cohort will provide important information on adverse health effects following prenatal and postnatal exposure to radioiodine and radiocesium isotopes, for which available epidemiological data are scant. Key words: Chernobyl, Chornobyl, exposure, in utero, early life, thyroid cancer, reliability.

Recent analysis of all solid cancer incidence (1958-2009) in the Life Span Study (LSS) revealed evidence of upward curvature in the radiation dose response among males but not females. Upward curvature in sex-averaged excess relative risk (ERR) for all solid cancer mortality (1950-2003) was also observed in the 0-2 Gy dose range. As reasons for non-linearity in the LSS are not completely understood, we conducted dose-response analyses for all solid cancer mortality and incidence applying similar methods [1958-2009 follow-up, DS02R1 doses, including subjects not-in-city (NIC) at the time of the bombing] and statistical models. Incident cancers were ascertained from Hiroshima and Nagasaki cancer registries, while cause of death was ascertained from death certificates throughout Japan. The study included 105,444 LSS subjects who were alive and not known to have cancer before January 1, 1958 (80,205 with dose estimates and 25,239 NIC subjects). Between 1958 and 2009, there were 3.1 million person-years (PY) and 22,538 solid cancers for incidence analysis and 3.8 million PY and 15,419 solid cancer deaths for mortality analysis. We fitted sex-specific ERR models adjusted for smoking to both types of data. Over the entire range of doses, solid cancer mortality dose-response exhibited a borderline significant upward curvature among males (P = 0.062) and significant upward curvature among females (P = 0.010); for solid cancer incidence, as before, we found a significant upward curvature among males (P = 0.001) but not among females (P = 0.624). The sex difference in magnitude of dose-response curvature was statistically significant for cancer incidence (P = 0.017) but not for cancer mortality (P = 0.781). The results of analyses in the 0-2 Gy range and restricted lower dose ranges generally supported inferences made about the sex-specific dose-response shape over the entire range of doses for each outcome. Patterns of sex-specific curvature by calendar period (1958-1987 vs. 1988-2009) and age at exposure (0-19 vs. 20-83) varied between mortality and incidence data, particularly among females, although for each outcome there was an indication of curvature among 0-19-year-old male survivors in both calendar periods and among 0-19-year-old female survivors in the recent period. Collectively, our findings indicate that the upward curvature in all solid cancer dose response in the LSS is neither specific to males nor to incidence data; its evidence appears to depend on the composition of sites comprising all solid cancer group and age at exposure or time. Further follow up and site-specific analyses of cancer mortality and incidence will be important to confirm the emerging trend in dose-response curvature among young survivors and unveil the contributing factors and sites.

© 2014 American Cancer Society. BACKGROUND: Recent studies of children and adolescents who were exposed to radioactive iodine-131 (I-131) after the 1986 Chernobyl nuclear accident in Ukraine exhibited a significant dose-related increase in the risk of thyroid cancer, but the association of radiation doses with tumor histologic and morphologic features is not clear. METHODS: A cohort of 11,664 individuals in Belarus who were aged ≤18 years at the time of the accident underwent 3 cycles of thyroid screening during 1997 to 2008. I-131 thyroid doses were estimated from individual thyroid activity measurements taken within 2 months after the accident and from dosimetric questionnaire data. Demographic, clinical, and tumor pathologic characteristics of the patients with thyroid cancer were analyzed using 1-way analysis of variance, chi-square tests or Fisher exact tests, and logistic regression. RESULTS: In total, 158 thyroid cancers were identified as a result of screening. The majority of patients had T1a and T1b tumors (93.7%), with many positive regional lymph nodes (N1; 60.6%) but few distant metastases (M1

Objective: To analyze the role of smoking, alcohol, coffee and tea in relation to thyroid cancer, we conducted a pooled analysis of 14 case - control studies conducted in the United States, Europe, and Asia. Methods: The sample consisted of 2725 thyroid cancer cases ( 2247 females, 478 males) and 4776 controls ( 3699 females, 1077 males). Conditional logistic regression with strati. cation on study, age at diagnosis, and gender was used to compute odds ratios and 95% confidence intervals. Results: Thyroid cancer risk was reduced in persons who had ever smoked. The relationship was more pronounced in current smokers (OR = 0.6, 95% CI = 0.6 - 0.7) than former smokers (OR = 0.9, 95% CI = 0.8 - 1.1). There were significant trends of reduced risk with greater duration and frequency of smoking. For consumption of wine and beer, there was a significant trend of decreasing thyroid cancer risk ( p = 0.02) that was not maintained after adjustment for current smoking (p = 0.12). Thyroid cancer risk was not associated with consumption of coffee or tea. These findings were consistent in both gender-specific and histology-specific (papillary and follicular) analyses. Conclusions: Pooled analyses of these geographically diverse case - control data indicate a reduced thyroid cancer risk associated with current smoking. A reduced risk associated with alcohol was eliminated after adjustment for smoking, and caffeinated beverages did not alter thyroid cancer risk.

Objective: To investigate risk factors for medullary thyroid cancer (MTC). Methods: We conducted a pooled analysis of 14 case-control studies from Europe, North America, and Asia, including 67 medullary cancers (43 women and 24 men) diagnosed in ten studies. Of the original 4776, we selected five controls per case matched on study, gender, and age. The pooled odds ratios (OR) were estimated using conditional logistic regression. Results: Education, weight, and body mass were not associated with MTC, but a significant positive relationship was seen with height (OR = 2.6 for highest vs lowest tertile). Significant excess risks were associated with a history of thyroid nodules (OR = 12), hypertension (OR = 2.3), gallbladder disease (OR = 4.3), and allergies (OR = 2.2). Among current smokers, a decreased risk of MTC was observed with increasing number of cigarettes. The risk was significantly elevated among women having a first birth after age 25 years, but no clear pattern emerged for other reproductive factors. Conclusions: Although the number of MTC was small, we detected several significant associations, including prior thyroid and other diseases.

COLLABORATORS (in alphabetical order of institution, study name, or location) Aichi Cancer Research Institute, Nagoya, Japan: N Hamajima, K Hirose, K Tajima; Albert Einstein College of Medicine, NY, USA: T Rohan; American Cancer Society, GA, USA: EE Calle, CW Jr Heath; Atlanta, Emory University, GA, USA: RJ Coates, JM Liff; Aviano Cancer Center, Pordenone, Italy: R Talamini; Mahidol University, Bangkok, Thailand: N Chantarakul, S Koetsawang, D Rachawat; Breast Tumor Collaborative Study, Johns Hopkins University, MD, USA: A Morabia, L Schuman, W Stewart, M Szklo; University of Queensland, Brisbane, Australia: C Bain, F Schofield, V Siskind; British Columbia Cancer Agency, BC, Canada: P Band, AJ Coldman, RP Gallagher, TG Hislop, P Yang; Cancer Research Center, University of Hawaii, Hawaii, USA: LM Kolonel, AMY Nomura; Canadian Cancer Registries Epidemiology Research Group, Canada: J Hu, KC Johnson, Y Mao; Catalán Institut of Oncology, Barcelona, Spain: S De Sanjosé; Centers for Disease Control & Prevention, GA, USA: N Lee, P Marchbanks, HW Ory, HB Peterson, HG Wilson, PA Wingo; Central Institute of Cancer Research, Berlin, Germany: K Ebeling, D Kunde, P Nishan; Centre for Genetic Epidemiology, University of Melbourne, Melbourne, Australia: JL Hopper; Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, MA, USA: G Colditz for Nurses' Health Study Research Group; Chennai Cancer Institute, Madras, India: V Gajalakshmi; Chiang Mai University, Chiang Mai, Thailand: N Martin, T Pardthaisong, S Silpisornkosol, C Theetranont; Chulalongkorn University, Bangkok, Thailand: B Boosiri, S Chutivongse, P Jimakorn, P Virutamasen, C Wongsrichanalai; Danish Cancer Society, Aalborg, Denmark: M Ewertz; Department of Medical Epidemiology, Karolinska Institute, Stockholm, Sweden: HO Adami, L Bergkvist, C Magnusson, I Persson; Deutsches Krebsforschungszentrum, Heidelberg, Germany: J Chang-Claude; University of Otago, Dunedin, New Zealand: C Paul, DCG Skegg, GFS Spears; European Institute of Oncology, Milan, Italy: P Boyle, T Evstifeeva; Fred Hutchinson Cancer Research Center, WA, USA: JR Daling, WB Hutchinson, K Malone, EA Noonan, JL Stanford, DB Thomas, NS Weiss, E White; French Multicentre Breast Study, INSERM, Villejuif, France: N Andrieu, A Brêmond, F Clavel, B Gairard, J Lansac, L Piana, R Renaud; Girona Cancer Registry, Girona, Spain: A Izquierdo, P Viladiu; Hospital General de Mexico, Mexico City, Mexico: HR Cuevas, P Ontiveros, A Palet, SB Salazar; Hospital Universitario, Cali, Colombia: N Aristizabal, A Cuadros; Icelandic Cancer Society, Reykjavik, Iceland: L Tryggvadottir, H Tulinius; INSERM, Institut Gustave-Roussey, Villejuif, France: A Bachelot, MG Lê; Institute of Cancer Research, Sutton and London School of Hygiene and Tropical Medicine, UK: J Peto; International Agency for Research in Cancer, Lyon, France: S Franceschi; Israel Chaim Sheba Medical Centre, Tel-Hashomer, Israel: F Lubin, B Modan, E Ron, Y Wax; Kaiser Permanente, CA, USA: GD Friedman, RA Hiatt; Institut universitaire de medecine sociale et preventive, Lausanne, Switzerland: F Levi; Cancer Research UK Genetic Epidemiology Laboratory, Leeds, UK: T Bishop; Institute of Oncology, Ljubljana, Slovenia: K Kosmelj, M Primic-Zakelj, B Ravnihar, J Stare; Loma Linda University, CA, USA: WL Beeson, G Fraser; Cancer Research UK Department of Mathematics, Statistics & Epidemiology, London: RD Bulbrook, J Cuzick, SW Duffy, IS Fentiman, JL Hayward, DY Wang; London School of Hygiene & Tropical Medicine, London, UK: AJ McMichael, K McPherson; Long Island Breast Cancer Study, NY, USA: RL Hanson, MC Leske, MC Mahoney, PC Nasca, AO Varma, AL Weinstein; University Hospital, Lund, Sweden: TR Moller, H Olsson, J Ranstam; Maastricht University, Maastricht, The Netherlands: RA Goldbohm, PA van den Brandt; University of Philippines, Manila, Philippines: RA Apelo, J Baens, JR de la Cruz, B Javier, LB Lacaya, CA Ngelangel; Istituto ‘Mario Negri', Milan, Italy: C La Vecchia, E Negri; Istituto Nazionale Tumori, Divisione di Statistica Medica e Biometria, Milan, Italy: E Marubini; Istituto di Statistica Medica e Biometria, Milan, Italy: M Ferraroni; Montpellier Cancer Centre & INSERM, Montpellier, France: M Gerber, S Richardson, C Segala; Nairobi Centre for Research in Reproduction, Nairobi, Kenya: D Gatei, P Kenya, A Kungu, JG Mati; National Cancer Institute, MD, USA: LA Brinton, R Hoover, C Schairer; National Institute of Child Health & Human Development, MD, USA: R Spirtas; National University of Singapore, Singapore: HP Lee; The Netherlands Cancer Institute, Amsterdam, The Netherlands: MA Rookus, FE van Leeuwen for the Netherlands Oral Contraceptives and Breast Cancer Study Group; New Jersey State Department of Health, NJ, USA: JA Schoenberg; New South Wales Cancer Council, Sydney, Australia: M McCredie; Columbia University School of Public Health, NY, USA: MD Gammon; Ontario Cancer Treatment & Research Foundation, Ontario, Canada: EA Clarke; Department of Public Health & Primary Care, Oxford, UK: L Jones, A Neil, M Vessey, D Yeates; Cancer Research UK Epidemiology Unit, Oxford, UK (Secretariat): P Appleby, E Banks, V Beral, D Bull, B Crossley, A Goodill, J Green, C Hermon, T Key, N Langston, C Lewis, G Reeves; Cancer Research UK/MRC/BHF Clinical Trial Service Unit & Epidemiological Studies Unit, Oxford, UK: R Collins, R Doll, R Peto; Radiation Effects Research Foundation, Hiroshima, Japan: K Mabuchi, D Preston; Royal College of General Practitioners Oral Contraception Study, London, UK: P Hannaford, C Kay; University of Costa Rica, San Jose, Costa Rica: L Rosero-Bixby; Shanghai Cancer Institute, Shanghai, China: YT Gao, F Jin, J-M Yuan; Shanghai Institute of Planned Parenthood Research, Shanghai, China: HY Wei, T Yun, C Zhiheng; Department of Public Health, Sydney, Australia: G Berry, J Cooper Booth, T Jelihovsky, R MacLennan, R Shearman; Tianjin Cancer Institute, Tianjin, China: Q-S Wang; Department of Public Health Sciences, Toronto, Canada: CJ Baines, AB Miller, C Wall; Tromso University, Tromso, Norway: E Lund, H Stalsberg; Vanderbilt University, TN, USA: XO Shu, W Zheng; University of Athens Medical School, Athens, Greece: K Katsouyanni, A Trichopoulou, D Trichopoulos; University of Chile, Santiago, Chile: A Dabancens, L Martinez, R Molina, O Salas; University of Edinburgh, Edinburgh, UK: FE Alexander; University of Minnesota School of Public Health, MN, USA: K Anderson, AR Folsom on behalf of the Iowa Women's Health Study; University of North Carolina at Chapel Hill, School of Public Health, NC, USA: BS Hulka; University of Nottingham, Nottingham, UK: CED Chilvers; University of Southern California, LA, USA: L Bernstein, S Enger, RW Haile, A Paganini-Hill, MC Pike, RK Ross, G Ursin, MC Yu; University of Wisconsin Comprehensive Cancer Center, WI, USA: MP Longnecker, P Newcomb for the 4 State Study; Vasteras, Sweden: L Bergkvist; World Health Organisation, Geneva, Switzerland: A Kalache; World Health Organisation, UNDP/UNFPA/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction, Geneva, Switzerland: TMM Farley, S Holck, O Meirik. Analysis and writing committee: Beral V, Bull D, Doll R, Peto R, Reeves G Steering committee: Skegg D (Chairman), Colditz G, Hulka B, La Vecchia C, Magnusson C, Muller A, Peterson B, Pike M, Thomas D, Van Leeuven M.; International audience; Alcohol and tobacco consumption are closely correlated and published results on their association with breast cancer have not always allowed adequately for confounding between these exposures. Over 80% of the relevant information worldwide on alcohol and tobacco consumption and breast cancer were collated, checked and analysed centrally. Analyses included 58,515 women with invasive breast cancer and 95,067 controls from 53 studies. Relative risks of breast cancer were estimated, after stratifying by study, age, parity and, where appropriate, women's age when their first child was born and consumption of alcohol and tobacco. The average consumption of alcohol reported by controls from developed countries was 6.0 g per day, i.e. about half a unit/drink of alcohol per day, and was greater in ever-smokers than never-smokers, (8.4 g per day and 5.0 g per day, respectively). Compared with women who reported drinking no alcohol, the relative risk of breast cancer was 1.32 (1.19-1.45, P/=45 g per day alcohol. The relative risk of breast cancer increased by 7.1% (95% CI 5.5-8.7%; P

Background Menarche and menopause mark the onset and cessation, respectively, of ovarian activity associated with reproduction, and affect breast cancer risk. Our aim was to assess the strengths of their effects and determine whether they depend on characteristics of the tumours or the affected women.Methods Individual data from 117 epidemiological studies, including 118 964 women with invasive breast cancer and 306 091 without the disease, none of whom had used menopausal hormone therapy, were included in the analyses. We calculated adjusted relative risks (RRs) associated with menarche and menopause for breast cancer overall, and by tumour histology and by oestrogen receptor expression.Findings Breast cancer risk increased by a factor of 1.050 (95% CI 1.044-1.057; p < 0.0001) for every year younger at menarche, and independently by a smaller amount (1.029, 1.025-1.032; p < 0.0001), for every year older at menopause. Premenopausal women had a greater risk of breast cancer than postmenopausal women of an identical age (RR at age 45-54 years 1.43, 1.33-1.52, p < 0.001). All three of these associations were attenuated by increasing adiposity among postmenopausal women, but did not vary materially by women's year of birth, ethnic origin, childbearing history, smoking, alcohol consumption, or hormonal contraceptive use. All three associations were stronger for lobular than for ductal tumours (p < 0.006 for each comparison). The effect of menopause in women of an identical age and trends by age at menopause were stronger for oestrogen receptor-positive disease than for oestrogen receptor-negative disease (p < 0.01 for both comparisons).Interpretation The effects of menarche and menopause on breast cancer risk might not be acting merely by lengthening women's total number of reproductive years. Endogenous ovarian hormones are more relevant for oestrogen receptor-positive disease than for oestrogen receptor-negative disease and for lobular than for ductal tumours.Funding Cancer Research UK.