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    Alcohol, tobacco and breast cancer - Collaborative reanalysis of individual data from 53 epidemiological studies, including 58 515 women with breast cancer and 95 067 women without the disease
    (2002-11-18) N. Hamajima; K. Hirose; K. Tajima; T. Rohan; E. E. Calle; C. W. Heath; R. J. Coates; J. M. Liff; R. Talamini; N. Chantarakul; S. Koetsawang; D. Rachawat; A. Morabia; L. Schuman; W. Stewart; M. Szklo; C. Bain; F. Schofield; V. Siskind; P. Band; A. J. Coldman; R. P. Gallagher; T. G. Hislop; P. Yang; L. M. Kolonel; A. M.Y. Nomura; J. Hu; K. C. Johnson; Y. Mao; S. De Sanjosé; N. Lee; P. Marchbanks; H. W. Ory; H. B. Peterson; H. G. Wilson; P. A. Wingo; K. Ebeling; D. Kunde; P. Nishan; J. L. Hopper; G. Colditz; V. Gajalakshmi; N. Martin; T. Pardthaisong; S. Silpisornkosol; C. Theetranont; B. Boosiri; S. Chutivongse; P. Jimakorn; P. Virutamasen; C. Wongsrichanalai; M. Ewertz; H. O. Adami; L. Bergkvist; C. Magnusson; I. Persson; J. Chang-Claude; C. Paul; D. C.G. Skegg; G. F.S. Spears; P. Boyle; T. Evstifeeva; J. R. Daling; W. B. Hutchinson; K. Malone; E. A. Noonan; J. L. Stanford; D. B. Thomas; N. S. Weiss; E. White; N. Andrieu; A. Brêmond; F. Clavel; B. Gairard; J. Lansac; L. Piana; R. Renaud; A. Izquierdo; P. Viladiu; H. R. Cuevas; P. Ontiveros; A. Palet; S. B. Salazar; N. Aristizabal; A. Cuadros; L. Tryggvadottir; H. Tulinius; A. Bachelot; M. G. Lê; J. Peto; S. Franceschi; F. Lubin; B. Modan; E. Ron; Y. Wax; G. D. Friedman; R. A. Hiatt; F. Levi; T. Bishop; Cancer Research UK; Aichi Cancer Center Hospital and Research Institute; Albert Einstein College of Medicine of Yeshiva University; American Cancer Society; Emory University; IRCCS Centro Di Riferimento Oncologico Aviano; Mahidol University; Johns Hopkins University; University of Queensland; British Columbia Cancer Agency; University of Hawaii System; Canadian Cancer Registries Epidemiology Research Group; Catalan Oncology Institute; Centers for Disease Control and Prevention; Max Delbruck Center for Molecular Medicine; University of Melbourne; Brigham and Women's Hospital; Cancer Institute India; Chiang Mai University; Chulalongkorn University; Kraeftens Bekaempelse; Karolinska Institutet; German Cancer Research Center; University of Otago; Istituto Europeo di Oncologia; Fred Hutchinson Cancer Research Center; Inserm; Girona Cancer Registry; Hospital General de Mexico; Hospital Universitario; Icelandic Cancer Society; Institut de Cancerologie Gustave Roussy; London School of Hygiene & Tropical Medicine; International Agency for Research on Cancer; Chaim Sheba Medical Center Israel; Kaiser Permanente; Institut Universitaire de Medecine Sociale et Preventive Lausanne; Onkoloski institut Ljubljana; Loma Linda University Adventist Health Sciences Center; Skånes universitetssjukhus; Maastricht University; University of the Philippines Manila; Istituto di Ricerche Farmacologiche Mario Negri; Fondazione IRCCS Istituto Nazionale dei Tumori, Milan; Istituto di Statistica Medica e Biometria; Nairobi Centre for Research in Reproduction; National Cancer Institute; National Institute of Child Health and Human Development; National University of Singapore; The Netherlands Cancer Institute; NEW JERSEY STATE DEPT OF HEALTH; New South Wales Cancer Council; Columbia University Medical Center; Ontario Cancer Treatment and Research Foundation; Clinical Trial Service Unit; Radiation Effects Research Foundation Hiroshima; Royal College of General Practitioners' Oral Contraception Study; Universidad de Costa Rica; Medical Center of Fudan University; Shanghai Institute of Planned Parenthood Research; Tianjin Cancer Institute and Hospital; Universitetet i Tromso; Vanderbilt University; University of Athens Medical School; Universidad de Chile; University of Edinburgh; University of Minnesota School of Public Health; The University of North Carolina at Chapel Hill; University of Nottingham; University of Southern California; University of Wisconsin; Organisation Mondiale de la Sante
    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<0.00001) for an intake of 35-44 g per day alcohol, and 1.46 (1.33-1.61, P<0.00001) for ≥45 g per day alcohol. The relative risk of breast cancer increased by 7.1% (95% Cl 5.5-8.7%; P<0.00001) for each additional 10 g per day intake of alcohol, i.e. for each extra unit or drink of alcohol consumed on a daily basis. This increase was the same in ever-smokers and never-smokers (7.1% per 10 g per day, P<0.00001, in each group). By contrast, the relationship between smoking and breast cancer was substantially confounded by the effect of alcohol. When analyses were restricted to 22255 women with breast cancer and 40832 controls who reported drinking no alcohol, smoking was not associated with breast cancer (compared to never-smokers, relative risk for ever-smokers=1.03, 95% Cl 0.98-1.07, and for current smokers=0.99, 0.92-1.05). The results for alcohol and for tobacco did not vary substantially across studies, study designs, or according to 15 personal characteristics of the women; nor were the findings materially confounded by any of these factors. If the observed relationship for alcohol is causal, these results suggest that about 4% of the breast cancers in developed countries are attributable to alcohol. In developing countries, where alcohol consumption among controls averaged only 0.4 g per day, alcohol would have a negligible effect on the incidence of breast cancer. In conclusion, smoking has littte or no independent effect on the risk of developing breast cancer; the effect of alcohol on breast cancer needs to be interpreted in the context of its beneficial effects, in moderation, on cardiovascular disease and its harmful effects on cirrhosis and cancers of the mouth, larynx, oesophagus and liver. © 2002 Cancer Research UK.
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    Breast cancer and combined oral contraceptives: Results from a multinational study
    (1990-01-01) Geoffrey Berry; Robert MacLennan; Rodney Shearman; Tatiana Jelihovsky; Joan Cooper Booth; Ramiro Molina; Luis Martinez; Oriana Salas; Alfredo Dabancens; Chen Zhiheng; Tao Yun; Hu Yong Wei; Alvaro Cuadros; Nubia Aristizabal; K. Ebeling; P. Nishan; D. Kunde; Baruch Modan; Elaine Ron; Ester Alfandary; J. G. Mati; Patrick Kenya; Alfred Kungu; D. Gatei; Hector Rodriguez Cuevas; Socorro Benavides Salazar; Antonio Palet; Patricia Ontiveros; Ruben A. Apelo; Julietta R. de la Cruz; Jose Baens; Benita Javier; Suporn Silpisornkosol; Tieng Pardthaisong; Nimit Martin; Choti Theetranont; Banpot Boosiri; Supawat Chutivongse; Pramuan Virutamasen; Chansuda Wongsrichanalai; Prasarn Jimakorn; Suporn Koetsawang; Daungdao Rachawat; Nivat Chantarakul; Helge Stalsberg; David B. Thomas; Elizabeth A. Noonan; Susan Holck; The University of Sydney; Facultad de Medicina de la Universidad de Chile; Shanghai Institute of Planned Parenthood Research; Hospital Universitario; Akademie der Wissenschaften der DDR; Chaim Sheba Medical Center Israel; University of Nairobi; Hospital General de Mexico; University of the Philippines Manila; Chiang Mai University; Chulalongkorn University; Mahidol University; Universitetet i Tromso; Fred Hutchinson Cancer Research Center; Organisation Mondiale de la Sante; Hospital del Salvador
    A collaborative, hospital-based case-control study was conducted at 12 participating centres in 10 countries. Based on data from personal interviews of 2, 116 women with newly diagnosed breast cancer and 12,077 controls, the relative risk of breast cancer in women who ever used oral contraceptives was estimated to be 1.15 (1.02, 1.29). Estimated values of this relative risk based on data from three developed and seven developing countries were 1.07 (0.91, 1.26) and 1.24 (1.05, 1.47) respectively; these estimates are not significantly different (P = 0.22). Estimates for women under and over age 35 were 1.26 (0.95, 1.66) and 1.12 (0.98, 1.27), respectively, and these estimates are also not significantly different (P= 0.38). Risk was highest in recent and current users and declined with time since last use regardless of duration of use. Risk did not increase with duration of use after stratifying on time since last use. Risk did not increase significantly with increasing duration of use before age 25 or before a first live birth. However, a relative risk of 1.5 that was of borderline statistical significance was observed in women who used oral contraceptives for more than 2 years before age 25. No single source of bias or confounding was identified that could explain the small increases in risk that were observed. Chance alone is also an unlikely explanation. The results could be due to a combination of chance and potential sources of bias, or they could represent a weak causal relationship. © Macmillan Press Ltd., 1990.
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    Breast cancer and hormonal contraceptives: Collaborative reanalysis of individual data on 53 297 women with breast cancer and 100 239 women without breast cancer from 54 epidemiological studies
    (1996-06-22) E. E. Calle; C. W. Heath; H. L. Miracle-McMahill; R. J. Coates; J. M. Liff; S. Franceschi; R. Talamini; N. Chantarakul; S. Koetsawang; D. RachawatRachawat; A. Morabia; L. Schuman; W. Stewart; M. Szklo; C. Bain; F. Schofield; V. Siskind; P. Band; A. J. Coldman; R. P. Gallagher; T. G. Hislop; P. Yang; S. W. Duffy; L. M. Kolonel; A. M.Y. Nomura; M. W. Oberle; H. W. Ory; H. B. Peterson; H. G. Wilson; P. A. Wingo; K. Ebeling; D. Kunde; P. Nishan; G. Colditz; N. Martin; T. Pardthaisong; S. Silpisornkosol; C. Theetranont; B. Boosiri; S. Chutivongse; P. Jimakorn; P. Virutamasen; C. Wongsrichanalai; A. J. McMichael; T. Rohan; M. Ewertz; C. Paul; D. C.G. Skegg; P. Boyle; M. Evstifeeva; J. R. Daling; K. Malone; E. A. Noonan; J. L. Stanford; D. B. Thomas; N. S. Weiss; E. White; N. Andrieu; A. Brêmond; F. Clavel; B. Gairard; J. Lansac; L. Piana; R. Renaud; S. R.P. Fine; H. R. Cuevas; P. Ontiveros; A. Palet; S. B. Salazar; N. Aristizabel; A. Cuadros; A. Bachelot; M. G. Lê; J. Deacon; J. Peto; C. N. Taylor; E. Alfandary; B. Modan; E. Ron; G. D. Friedman; R. A. Hiatt; T. Bishop; J. Kosmelj; M. Primic-Zakelj; B. Ravnihar; J. Stare; W. L. Beeson; G. Fraser; D. S. Allen; R. D. Bulbrook; J. Cuzick; I. S. Fentiman; J. L. Hayward; D. Y. Wang; R. L. Hanson; M. C. Leske; M. C. Mahoney; P. C. Nasca; A. O. Varma; A. L. Weinstein; American Cancer Society; Emory University; IRCCS Centro Di Riferimento Oncologico Aviano; Mahidol University; Johns Hopkins University; University of Queensland; British Colombia Cancer Agency; MRC Biostatistics Unit; University of Hawaii System; Centers for Disease Control and Prevention; Central Institute of Cancer Research; Brigham and Women's Hospital; Chiang Mai University; Chulalongkorn University; Food Science Australia; Kraeftens Bekaempelse; University of Otago; Istituto Europeo di Oncologia; Fred Hutchinson Cancer Research Center; Inserm; Holly Lodge; Hospital General de Mexico; Hospital Universitario; Institut de Cancerologie Gustave Roussy; The Institute of Cancer Research, London; Israel Chaim Sheba Medical Center; Kaiser Permanente; Cancer Research UK; Onkoloski institut Ljubljana; Loma Linda University Adventist Health Sciences Center; Skånes universitetssjukhus; Maastricht University; University of the Philippines Manila; Istituto 'Mario Negri'; Divisione di Statistica Medica e Biometria; Istituto di Statistica Medica e Biometria; Nairobi Centre for Research in Reproduction; National Cancer Institute; National Institute of Child Health and Human Development; National University of Singapore; The Netherlands Cancer Institute; NEW JERSEY STATE DEPT OF HEALTH; Columbia University Medical Center; Ontario Cancer Treatment and Research Foundation; Clinical Trial Service Unit; University of Costa Rica; Medical Center of Fudan University; Shanghai Institute of Planned Parenthood Research; Tianjin Cancer Institute and Hospital; Universitetet i Tromso; Universidad de Chile; University of Edinburgh; The University of North Carolina at Chapel Hill; University of Nottingham; University of Southern California; Uppsala Universitet; University of Wisconsin; Organisation Mondiale de la Sante
    Background: The Collaborative Group on Hormonal Factors in Breast Cancer has brought together and reanalysed the worldwide epidemiological evidence on the relation between breast cancer risk and use of hormonal contraceptives. Methods: Individual data on 53 297 women with breast cancer and 100 239 women without breast cancer from 54 studies conducted in 25 countries were collected, checked, and analysed centrally. Estimates of the relative risk for breast cancer were obtained by a modification of the Mantel-Haenszel method. All analyses were stratified by study, age at diagnosis, parity, and, where appropriate, the age a woman was when her first child was born, and the age she was when her risk of conception ceased. Findings: The results provide strong evidence for two main conclusions. First, while women are taking combined oral contraceptives and in the 10 years after stopping there is a small increase in the relative risk of having breast cancer diagnosed (relative risk [95% Cl] in current users 1·24 [1·15-1·33], 2p<0·00001; 1-4 years after stopping 1·6 [1·08-1·23], 2p=0·00001; 5-9 years after stopping 1·07 [1·02-1·13], 2p=0·009). Second, there is no significant excess risk of having breast cancer diagnosed 10 or more years after stopping use (relative risk 1·01 [0·96-1·05], NS). The cancers diagnosed in women who had used combined oral contraceptives were less advanced clinically than those diagnosed in women who had never used these contraceptives: for ever-users compared with never-users, the relative risk for tumours that had spread beyond the breast compared with localised tumours was 0·88 (0·81-0·95; 2p=0·002). There was no pronounced variation in the results for recency of use between women with different background risks of breast cancer, including women from different countries and ethnic groups, women with different reproductive histories, and those with or without a family history of breast cancer. The studies included in this collaboration represent about 90% of the epidemiological information on the topic, and what is known about the other studies suggests that their omission has not materially affected the main conclusions. Other features of hormonal contraceptive use such as duration of use, age at first use, and the dose and type of hormone within the contraceptives had little additional effect on breast cancer risk, once recency of use had been taken into account. Women who began use before age 20 had higher relative risks of having breast cancer diagnosed while they were using combined oral contraceptives and in the 5 years after stopping than women who began use at older ages, but the higher relative risks apply at ages when breast cancer is rare and, for a given duration of use, earlier use does not result in more cancers being diagnosed than use beginning at older ages. Because breast cancer incidence rises steeply with age, the estimated excess number of cancers diagnosed in the period between starting use and 10 years after stopping increases with age at last use: for example, among 10 000 women from Europe or North America who used oral contraceptives from age 16 to 19, from age 20 to 24, and from age 25 to 29, respectively, the estimated excess number of cancers diagnosed up to 10 years after stopping use is 0·5 (95% Cl 0·3-0·7), 1·5 (0·7-2·3), and 4·7 (2·7-6·7). Up to 20 years after cessation of use the difference between ever-users and never-users is not so much in the total number of cancers diagnosed, but in their clinical presentation, with the breast cancers diagnosed in ever-users being less advanced clinically than those diagnosed in never-users. The relation observed between breast cancer risk and hormone exposure is unusual, and it is not possible to infer from these data whether it is due to an earlier diagnosis of breast cancer in ever-users, the biological effects of hormonal contraceptives, or a combination of reasons. Interpretation: Women who are currently using combined oral contraceptives or have used them in the past 10 years are at a slightly increased risk of having breast cancer diagnosed, although the additional cancers diagnosed tend to be localised to the breast. There is no evidence of an increase in the risk of having breast cancer diagnosed 10 or more years after cessation of use, and the cancers diagnosed then are less advanced clinically than the cancers diagnosed in never-users.
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    Breast cancer and hormone replacement therapy: Collaborative reanalysis of data from 51 epidemiological studies of 52,705 women with breast cancer and 108,411 women without breast cancer
    (1997-10-11) E. E. Calle; C. W. Heath; R. J. Coates; J. M. Liff; S. Franceschi; R. Talamini; N. Chantarakul; S. Koetsawang; D. Rachawat; A. Morabia; L. Schuman; W. Stewart; M. Szklo; C. Bain; F. Schofield; V. Siskind; P. Band; A. J. Coldman; R. P. Gallagher; T. G. Hislop; P. Yang; S. W. Duffy; L. M. Kolonel; A. M.Y. Nomura; M. W. Oberle; H. W. Ory; H. B. Peterson; H. G. Wilson; P. A. Wingo; K. Ebeling; D. Kunde; P. Nishan; G. Colditz; N. Martin; T. Pardthaisong; S. Silpisornkosol; C. Theetranont; B. Boosiri; S. Chutivongse; P. Jimakorn; P. Virutamasen; C. Wongsrichanalai; A. J. McMichael; T. Rohan; M. Ewertz; C. Paul; D. C.G. Skegg; G. F.S. Spears; P. Boyle; M. Evstifeeva; J. R. Daling; W. B. Hutchinson; K. Malone; E. A. Noonan; J. L. Stanford; D. B. Thomas; N. S. Weiss; E. White; N. Andrieu; A. Bràmond; F. Clavel; B. Gairard; J. Lansac; L. Piana; R. Renaud; S. R.P. Fine; H. R. Cuevas; P. Ontiveros; A. Palet; S. B. Salazar; N. Aristizabel; A. Cuadros; A. Bachelot; M. G. Lê; J. Deacon; J. Peto; C. N. Taylor; E. Alfandary; B. Modan; E. Ron; G. D. Friedman; R. A. Hiatt; T. Bishop; J. Kosmelj; M. Primic-Zakelj; B. Ravnihar; J. Stare; W. L. Beeson; G. Fraser; R. D. Bulbrook; J. Cuzick; I. S. Fentiman; J. L. Hayward; D. Y. Wang; R. L. Hanson; M. C. Leske; M. C. Mahoney; P. C. Nasca; A. O. Varma; A. L. Weinstein; American Cancer Society; Emory University; IRCCS Centro Di Riferimento Oncologico Aviano; Mahidol University; Johns Hopkins University; University of Queensland; British Colombia Cancer Agency; MRC Biostatistics Unit; University of Hawaii System; Centers for Disease Control and Prevention; Central Institute of Cancer Research; Harvard Medical School; Chiang Mai University; Chulalongkorn University; Food Science Australia; Kraeftens Bekaempelse; University of Otago; Istituto Europeo di Oncologia; Fred Hutchinson Cancer Research Center; Inserm; Holly Lodge; Hospital General de Mexico; Hospital Universitario; Institut de Cancerologie Gustave Roussy; The Institute of Cancer Research, London; Israel Chaim Sheba Medical Center; Kaiser Permanente; Cancer Research UK; Onkoloski institut Ljubljana; Loma Linda University Adventist Health Sciences Center; Long Island Breast Cancer Study; Skånes universitetssjukhus; Maastricht University; University of the Philippines Manila; Istituto 'Mario Negri'; Divisione di Statistica Medica e Biometria; Istituto di Statistica Medica e Biometria; Nairobi Centre for Research in Reproduction; National Cancer Institute; National Institute of Child Health and Human Development; National University of Singapore; The Netherlands Cancer Institute; NEW JERSEY STATE DEPT OF HEALTH; Columbia University Medical Center; Ontario Cancer Treatment and Research Foundation; Clinical Trial Service Unit; Royal College of General Practitioners Oral Contraception Study; University of Costa Rica; Medical Center of Fudan University; Shanghai Institute of Planned Parenthood Research; Tianjin Cancer Institute and Hospital; Universitetet i Tromso; Universidad de Chile; University of Edinburgh; The University of North Carolina at Chapel Hill; University of Nottingham; University of Southern California; University of Wisconsin; Organisation Mondiale de la Sante; Karolinska Institutet; Institut Universitaire de Medecine Sociale et Preventive Lausanne; London School of Hygiene & Tropical Medicine; Radiation Effects Research Foundation Hiroshima; University of Athens Medical School
    Background. The Collaborative Group on Hormonal Factors in Breast Cancer has brought together and reanalysed about 90% of the worldwide epidemiological evidence on the relation between risk of breast cancer and use of hormone replacement therapy (HRT). Methods. Individual data on 52,705 women with breast cancer and 108,411 women without breast cancer from 51 studies in 21 countries were collected, checked, and analysed centrally. The main analyses are based on 53,865 postmenopausal women with a known age at menopause, of whom 17,830 (33%) had used HRT at some time. The median age at first use was 48 years, and 34% of ever-users had used HRT for 5 years or longer. Estimates of the relative risk of breast cancer associated with the use of HRT were obtained after stratification of all analyses by study, age at diagnosis, time since menopause, body-mass index, parity, and the age a woman was when her first child was born. Findings. Among current users of HRT or those who ceased use 1-4 years previously, the relative risk of having breast cancer diagnosed increased by a factor of 1.023 (95% CI 1.011-1.036; 2p = 0.0002) for each year of use; the relative risk was 1.35 (1.21-1.49; 2p = 0.00001) for women who had used HRT for 5 years or longer (average duration of use in this group 11 years). This increase is comparable with the effect on breast cancer of delaying menopause, since among never-users of HRT the relative risk of breast cancer increases by a factor of 1.028 (95% CI 1.021-1.034) for each year older at menopause. 5 or more years after cessation of HRT use, there was no significant excess of breast cancer overall or in relation to duration of use. These main findings did not vary between individual studies. Of the many factors examined that might affect the relation between breast cancer risk and use of HRT, only a woman's weight and body-mass index had a material effect: the increase in the relative risk of breast dancer associated with long durations of use in current and recent users was greater for women of lower than of higher weight or body-mass index. There was no marked variation in the results according to hormonal type or dose but little information was available about long durations of use of any specific preparation. Cancers diagnosed in women who had ever used HRT tended to be less advanced clinically than those diagnosed in never-users. In North America and Europe the cumulative incidence of breast cancer between the ages of 50 and 70 in never-users of HRT is about 45 per 1000 women. The cumulative excess numbers of breast cancers diagnosed between these ages per 1000 women who began use of HRT at age 50 and used it for 5, 10, and 15 years, respectively, are estimated to be 2 (95% CI 1-3), 6 (3-9), and 12 (5-20). Whether HRT affects mortality from breast cancer is not known. Interpretation. The risk of having breast cancer diagnosed is increased in women using HRT and increases with increasing duration of use. This effect is reduced after cessation of use of HRT and has largely, if not wholly, disappeared after about 5 years. These findings should be considered in the context of the benefits and other risks associated with the use of HRT.
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    Guidelines for the use and interpretation of assays for monitoring autophagy
    (2012-04-01) Daniel J. Klionsky; Fabio C. Abdalla; Hagai Abeliovich; Robert T. Abraham; Abraham Acevedo-Arozena; Khosrow Adeli; Lotta Agholme; Maria Agnello; Patrizia Agostinis; Julio A. Aguirre-Ghiso; Hyung Jun Ahn; Ouardia Ait-Mohamed; Slimane Ait-Si-Ali; Takahiko Akematsu; Shizuo Akira; Hesham M. Al-Younes; Munir A. Al-Zeer; Matthew L. Albert; Roger L. Albin; Javier Alegre-Abarrategui; Maria Francesca Aleo; Mehrdad Alirezaei; Alexandru Almasan; Maylin Almonte-Becerril; Atsuo Amano; Ravi Amaravadi; Shoba Amarnath; Amal O. Amer; Nathalie Andrieu-Abadie; Vellareddy Anantharam; David K. Ann; Shailendra Anoopkumar-Dukie; Hiroshi Aoki; Nadezda Apostolova; Giuseppe Arancia; John P. Aris; Katsuhiko Asanuma; Nana Y.O. Asare; Hisashi Ashida; Valerie Askanas; David S. Askew; Patrick Auberger; Misuzu Baba; Steven K. Backues; Eric H. Baehrecke; Ben A. Bahr; Xue Yuan Bai; Yannick Bailly; Robert Baiocchi; Giulia Baldini; Walter Balduini; Andrea Ballabio; Bruce A. Bamber; Edward T.W. Bampton; Gábor Bánhegyi; Clinton R. Bartholomew; Diane C. Bassham; Robert C. Bast; Henri Batoko; Boon Huat Bay; Isabelle Beau; Daniel M. Béchet; Thomas J. Begley; Christian Behl; Christian Behrends; Soumeya Bekri; Bryan Bellaire; Linda J. Bendall; Luca Benetti; Laura Berliocchi; Henri Bernardi; Francesca Bernassola; Sébastien Besteiro; Ingrid Bhatia-Kissova; Xiaoning Bi; Martine Biard-Piechaczyk; Janice S. Blum; Lawrence H. Boise; Paolo Bonaldo; David L. Boone; Beat C. Bornhauser; Karina R. Bortoluci; Ioannis Bossis; Frédéric Bost; Jean Pierre Bourquin; Patricia Boya; Michaël Boyer-Guittaut; Peter V. Bozhkov; Nathan R. Brady; Claudio Brancolini; Andreas Brech; Jay E. Brenman; University of Michigan, Ann Arbor; Universidade Federal de Sao Carlos; Hebrew University of Jerusalem; Pfizer Inc.; MRC Mammalian Genetics Unit; Hospital for Sick Children University of Toronto; Linkopings universitet; Universita degli Studi di Palermo; KU Leuven; New York University; Korea Institute of Science and Technology; Universite Paris 7- Denis Diderot; York University; Osaka University; The University of Jordan; Max Planck Institute for Infection Biology; Institut Pasteur, Paris; VAAAHS; University of Oxford; Universita degli Studi di Brescia, Facolta di Medicina e Chirurgia; Scripps Research Institute; Cleveland Clinic Foundation; Centro de Investigacion y de Estudios Avanzados; University of Pennsylvania; National Cancer Institute; Ohio State University; Universite Paul Sabatier Toulouse III; Iowa State University; City of Hope National Med Center; Griffith University; Niigata University; Universitat de Valencia, Facultad de Medicina y Odontologia; Istituto Superiore Di Sanita, Rome; 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Peking University Health Science Center; University of California, Berkeley; Goteborgs Universitet; Max Planck Institut fur Psychiatrie; Centre Hospitalier Universitaire de Nice; Istituto Neurologico Mediterraneo Neuromed, Pozzilli; The Cancer Institute of New Jersey; Universite de Lyon; Panepistimio Kritis; Santo Tomas University; Johannes Gutenberg Universitat Mainz; University of Rzeszow
    In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field. © 2012 Landes Bioscience.
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    Histologic types of breast carcinoma in relation to international variation and breast cancer risk factors
    (1989-01-01) H. Stalsberg; D. B. Thomas; E. A. Noonan; G. Berry; R. Maclennan; R. Shearman; T. Jelihovsky; J. Cooper Booth; R. Molina; L. Martinez; O. Salas; A. Dabancens; Chen Zhiheng; Tao Yun; Hu Yong Wei; A. Cuadros; N. Aristizabal; K. Ebeling; P. Nishan; D. Kunde; B. Modan; E. Ron; E. Alfandary; J. G. Mati; P. Kenya; A. Kungu; D. Gatei; H. Rodriguez Cuevas; S. Benavides Salazar; A. Palet; P. Ontiveros; R. A. Apelo; J. R.La De Cruz; J. Baens; B. Javier; Suporn Silpisornkosol; Tieng Pardthaisong; Nimit Martin; Choti Theetranont; Banpot Boosiri; Supawat Chutivongse; Pramuan Virutamasen; Chansuda Wongsrichanalai; Prasarn Jimakorn; Suporn Koetsawang; Daungdao Rachawat; Nivat Chantarakul; S. Holck; Universitetet i Tromso; Fred Hutchinson Cancer Research Center; The University of Sydney; Facultad de Medicina de la Universidad de Chile; Shanghai Institute of Planned Parenthood Research; Hospital Universitario; Academy of Sciences; Chaim Sheba Medical Center Israel; University of Nairobi; Hospital General de Mexico; University of the Philippines Manila; Chiang Mai University; Chulalongkorn University; Mahidol University; Organisation Mondiale de la Sante; Development and Research Training in Human Reproduction
    Associations between breast cancer risk factors and histologic types of invasive breast carcinoma were studied in 2,728 patients. Lobular and tubular carcinomas occurred with increased relative frequency in most high‐risk groups. The proportion of these types increased with age to a maximum at 45–49 years and decreased in the following decade. Significantly increased proportions of lobular and tubular carcinomas were also associated with high‐risk countries, prior benign breast biopsy, bilateral breast cancer, concurrent mammary dysplasia, high age at first live birth, never‐pregnant patients compared to those with a first live birth before age 20, private pay status, and length of education. Nonsignificant increases were associated with family history of breast cancer, less than 5 live births, less than 25 months total of breast feeding, use of oral contraceptives or IUD, and high occupational class. As a general trend, the higher the overall relative risk, the higher the proportion of lobular and tubular carcinomas. The occurrence of other histologic types also increased with increased breast cancer risk, but to a smaller degree than for lobular/tubular carcinomas. It is suggested that all hormonally related, socio‐economic and geographic risk factors exert their effect by selectively increasing the number of lobular cells at risk. Family history of breast cancer and age over 49 years did not follow the general trend of parallel increases in the proportion of lobular/tubular carcinomas and breast cancer risk, and may operate through other mechanisms. Copyright © 1989 Wiley‐Liss, Inc., A Wiley Company
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    Menarche, menopause, and breast cancer risk: Individual participant meta-analysis, including 118 964 women with breast cancer from 117 epidemiological studies
    (2012-01-01) N. Hamajima; K. Hirose; K. Tajima; T. Rohan; C. M. Friedenreich; E. E. Calle; S. M. Gapstur; A. V. Patel; R. J. Coates; J. M. Liff; R. Talamini; N. Chantarakul; S. Koetsawang; D. Rachawat; Y. Marcou; E. Kakouri; S. W. Duffy; A. Morabia; L. Schuman; W. Stewart; M. Szklo; P. F. Coogan; J. R. Palmer; L. Rosenberg; P. Band; A. J. Coldman; R. P. Gallagher; T. G. Hislop; P. Yang; S. R. Cummings; K. Canfell; F. Sitas; P. Chao; J. Lissowska; P. L. Horn-Ross; E. M. John; L. M. Kolonel; A. M.Y. Nomura; R. Ghiasvand; J. Hu; K. C. Johnson; Y. Mao; V. Beral; D. Bull; K. Callaghan; B. Crossley; A. Goodill; J. Green; C. Hermon; T. Key; I. Lindgard; B. Liu; K. Pirie; G. Reeves; R. Collins; R. Doll; R. Peto; T. Bishop; I. S. Fentiman; S. De Sanjosé; C. A. Gonzalez; N. Lee; P. Marchbanks; H. W. Ory; H. B. Peterson; P. Wingo; K. Ebeling; D. Kunde; P. Nishan; J. L. Hopper; H. Eliassen; S. Hankinson; V. Gajalakshmi; N. Martin; T. Pardthaisong; S. Silpisornkosol; C. Theetranont; B. Boosiri; S. Chutivongse; P. Jimakorn; P. Virutamasen; C. Wongsrichanalai; A. Neugut; R. Santella; C. J. Baines; N. Kreiger; A. B. Miller; C. Wall; A. Tjonneland; T. Jorgensen; C. Stahlberg; A. Tønnes Pedersen; D. Flesch-Janys; N. Hakansson; J. Cauley; I. Heuch; H. O. Adami; I. Persson; E. Weiderpass; C. Magnusson; Aichi Cancer Center Hospital and Research Institute; Albert Einstein College of Medicine of Yeshiva University; Alberta Health Services; American Cancer Society; Emory University; IRCCS Centro Di Riferimento Oncologico Aviano; Mahidol University; Bank of Cyprus Group Oncology Centre; Barts and The London Queen Mary's School of Medicine and Dentistry; Johns Hopkins University; Boston University; British Columbia Cancer Agency; California Pacific Medical Center; Cancer Council New South Wales; Institute of Oncology, Warsaw; Cancer Prevention Institute of California; University of Hawaii System; University of Tehran; Canadian Cancer Registries Epidemiology Research Group; Cancer Research UK; Clinical Trial Service Unit; Catalan Oncology Institute; Centers for Disease Control and Prevention; Max Delbruck Center for Molecular Medicine; University of Melbourne; Brigham and Women's Hospital; Cancer Institute India; Chiang Mai University; Chulalongkorn University; Columbia University in the City of New York; Dalla Lana School of Public Health; Institute of Cancer Epidemiology - Denmark; Danish Nurse Cohort Study; Universitatsklinikum Hamburg-Eppendorf und Medizinische Fakultat; Karolinska Institutet; University of Pittsburgh; Universitetet i Bergen; German Cancer Research Center; University of Otago; National Cancer Center Tokyo; Fred Hutchinson Cancer Research Center; Epidemiology Unit and Girona Cancer Registry (UERCG); UCL; Hospital General de Mexico; Hospital Universitario; Icelandic Cancer Society; Imperial College London; Institut de Cancerologie Gustave Roussy; Inserm; Instituto Nacional de Salud Publica; International Agency for Research on Cancer; International Prevention Research Institute; Chaim Sheba Medical Center Israel; Kaiser Permanente; Institut Universitaire de Medecine Sociale et Preventive Lausanne; Onkoloski institut Ljubljana; Loma Linda University Adventist Health Sciences Center; London School of Hygiene & Tropical Medicine; Long Island Breast Cancer Study; Skånes universitetssjukhus; Maastricht University; ISPO; Icahn School of Medicine at Mount Sinai; University of the Philippines Manila; Universita degli Studi di Milano; Fondazione IRCCS Istituto Nazionale dei Tumori, Milan; Istituto di Statistica Medica e Biometria; Memorial Sloan-Kettering Cancer Center; Nairobi Centre for Research in Reproduction; National Cancer Institute; Australian National University; National Institute of Child Health and Human Development; National University of Singapore; The Netherlands Cancer Institute; New Jersey State Department of Health; Norwegian Institute of Public Health; Department of Public Health; Radiation Effects Research Foundation Hiroshima; Royal College of General Practitioners Oral Contraception Study; Roswell Park Cancer Institute; Universidad de Costa Rica; Medical Center of Fudan University; Shanghai Institute of Planned Parenthood Research; Cyprus Institute of Neurology and Genetics; Wuhan University; Tianjin Cancer Institute and Hospital; Tohoku University School of Medicine; Universitetet i Tromso; Vanderbilt University; University Medical Center Utrecht; University of Athens Medical School; University of California, San Francisco; Universidad de Chile; University of Edinburgh; University of Minnesota School of Public Health; The University of North Carolina at Chapel Hill; University of Nottingham; Universita degli Studi di Padova; University of Queensland; University of Pennsylvania, School of Medicine; University of Southern California; Syddansk Universitet; University of Toronto; Women's Health Initiative; Organisation Mondiale de la Sante; Yamagata University Faculty of Medicine
    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 receptorpositive disease than for oestrogen receptor-negative disease and for lobular than for ductal tumours.
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    Ovarian cancer and body size: Individual participant meta-analysis including 25,157 women with ovarian cancer from 47 epidemiological studies
    (2012-04-01) V. Beral; C. Hermon; R. Peto; G. Reeves; L. Brinton; P. Marchbanks; E. Negri; R. B. Ness; P. H.M. Peeters; M. Vessey; E. E. Calle; S. M. Gapstur; A. V. Patel; L. Dal Maso; R. Talamini; A. Chetrit; G. Hirsh-Yechezkel; F. Lubin; S. Sadetzki; N. Allen; D. Bull; K. Callaghan; B. Crossley; K. Gaitskell; A. Goodill; J. Green; T. Key; K. Moser; R. Collins; R. Doll; C. A. Gonzalez; N. Lee; H. W. Ory; H. B. Peterson; P. A. Wingo; N. Martin; T. Pardthaisong; S. Silpisornkosol; C. Theetranont; B. Boosiri; S. Chutivongse; P. Jimakorn; P. Virutamasen; C. Wongsrichanalai; A. Tjonneland; L. Titus-Ernstoff; T. Byers; T. Rohan; B. J. Mosgaard; D. Yeates; J. L. Freudenheim; J. Chang-Claude; R. Kaaks; K. E. Anderson; A. Folsom; M. A. Rossing; D. B. Thomas; N. S. Weiss; E. Riboli; F. Clavel-Chapelon; D. Cramer; K. Robien; S. S. Tworoger; D. Cramer; S. E. Hankinson; S. S. Tworoger; S. Franceschi; C. La Vecchia; C. Magnusson; T. Riman; E. Weiderpass; A. Wolk; L. J. Schouten; P. A. Van den Brandt; N. Chantarakul; S. Koetsawang; D. Rachawat; D. Palli; A. Black; A. Berrington de Gonzalez; D. M. Freedman; P. Hartge; A. W. Hsing; J. V. Lacey; R. N. Hoover; C. Schairer; S. Graff-Iversen; R. Selmer; C. J. Bain; A. C. Green; D. M. Purdie; V. Siskind; P. M. Webb; American Cancer Society; IRCCS Centro Di Riferimento Oncologico Aviano; The Gertner Institute; Cancer Epidemiology Unit; Clinical Trial Service Unit; Institute Catala Oncologia; Centers for Disease Control and Prevention; Chiang Mai University; Chulalongkorn University; Institute of Cancer Epidemiology - Denmark; Geisel School of Medicine at Dartmouth; Colorado School of Public Health; Albert Einstein College of Medicine of Yeshiva University; Amtssygehuset i Herlev; Department of Public Health; University at Buffalo, State University of New York; German Cancer Research Center; University of Minnesota School of Public Health; University of Washington, Seattle; Imperial College London; Centre de recherche en epidemiologie et sante des populations; Harvard Medical School; Brigham and Women's Hospital; Channing Laboratory; International Agency for Research on Cancer; Universita degli Studi di Milano; Karolinska Institutet; Maastricht University; Mahidol University; Centro Per Lo Studio E La Prevenzione Oncologica; National Cancer Institute; Norwegian Institute of Public Health; Queensland Institute of Medical Research; Roswell Park Cancer Institute; Royal College of General Practitioners' Oral Contraception Study; Curtin University; University of Texas System; University of Massachusetts System; Boston University; Stanford University; University of Athens Medical School; Universidad de Chile; University of Hawaii System; Skånes universitetssjukhus; University of Pennsylvania; University Medical Center Utrecht; University of Southern California; University of Toronto; Universitetet i Tromso; George Washington University; Vanderbilt University; Organisation Mondiale de la Sante; Yale University
    Background: Only about half the studies that have collected information on the relevance of women's height and body mass index to their risk of developing ovarian cancer have published their results, and findings are inconsistent. Here, we bring together the worldwide evidence, published and unpublished, and describe these relationships. Methods and Findings: Individual data on 25,157 women with ovarian cancer and 81,311 women without ovarian cancer from 47 epidemiological studies were collected, checked, and analysed centrally. Adjusted relative risks of ovarian cancer were calculated, by height and by body mass index. Ovarian cancer risk increased significantly with height and with body mass index, except in studies using hospital controls. For other study designs, the relative risk of ovarian cancer per 5 cm increase in height was 1.07 (95% confidence interval [CI], 1.05-1.09; p < 0.001); this relationship did not vary significantly by women's age, year of birth, education, age at menarche, parity, menopausal status, smoking, alcohol consumption, having had a hysterectomy, having first degree relatives with ovarian or breast cancer, use of oral contraceptives, or use of menopausal hormone therapy. For body mass index, there was significant heterogeneity (p < 0.001) in the findings between ever-users and never-users of menopausal hormone therapy, but not by the 11 other factors listed above. The relative risk for ovarian cancer per 5 kg/m 2 increase in body mass index was 1.10 (95% CI, 1.07-1.13; p < 0.001) in never-users and 0.95 (95% CI, 0.92-0.99; p = 0.02) in ever-users of hormone therapy. Conclusions: Ovarian cancer is associated with height and, among never-users of hormone therapy, with body mass index. In high-income countries, both height and body mass index have been increasing in birth cohorts now developing the disease. If all other relevant factors had remained constant, then these increases in height and weight would be associated with a 3% increase in ovarian cancer incidence per decade. © 2012 Collaborative Group on Epidemiological Studies of Ovarian Cancer.
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    Ovarian cancer and oral contraceptives: collaborative reanalysis of data from 45 epidemiological studies including 23 257 women with ovarian cancer and 87 303 controls
    (2008-01-26) V. Beral; R. Doll; C. Hermon; R. Peto; G. Reeves; L. Brinton; A. C. Green; P. Marchbanks; E. Negri; R. Ness; P. Peeters; M. Vessey; E. E. Calle; C. Rodriguez; L. Dal Maso; R. Talamini; D. Cramer; S. E. Hankinson; S. S. Tworoger; A. Chetrit; G. Hirsh-Yechezkel; F. Lubin; S. Sadetzki; P. Appleby; E. Banks; A. Berrington de Gonzalez; D. Bull; B. Crossley; A. Goodill; I. Green; J. Green; T. Key; R. Collins; C. A. Gonzalez; N. Lee; H. W. Ory; H. B. Peterson; P. A. Wingo; N. Martin; T. Pardthaisong; S. Silpisornkosol; C. Theetranont; B. Boosiri; S. Chutivongse; P. Jimakorn; P. Virutamasen; C. Wongsrichanalai; L. Titus-Ernstoff; B. J. Mosgaard; D. Yeates; J. Chang-Claude; M. A. Rossing; D. Thomas; N. Weiss; S. Franceschi; C. La Vecchia; H. O. Adami; C. Magnusson; T. Riman; E. Weiderpass; A. Wolk; L. A. Brinton; D. M. Freedman; P. Hartge; J. M. Lacey; R. Hoover; L. J. Schouten; P. A. van den Brandt; N. Chantarakul; S. Koetsawang; D. Rachawat; S. Graff-Iversen; R. Selmer; C. J. Bain; D. M. Purdie; V. Siskind; P. M. Webb; S. E. McCann; P. Hannaford; C. Kay; C. W. Binns; A. H. Lee; M. Zhang; P. Nasca; P. F. Coogan; L. Rosenberg; J. Kelsey; R. Paffenbarger; A. Whittemore; K. Katsouyanni; A. Trichopoulou; D. Trichopoulos; A. Tzonou; A. Dabancens; L. Martinez; R. Molina; O. Salas; M. T. Goodman; G. Laurie; American Cancer Society; IRCCS Centro Di Riferimento Oncologico Aviano; Brigham and Women's Hospital; Channing Laboratory; The Gertner Institute; Cancer Epidemiology Unit; Clinical Trial Service Unit; Institute Catala Oncologia; Centers for Disease Control and Prevention; Chiang Mai University; Chulalongkorn University; Geisel School of Medicine at Dartmouth; Amtssygehuset i Herlev; Department of Public Health; German Cancer Research Center; University of Washington, Seattle; International Agency for Research on Cancer; Universita degli Studi di Milano; Karolinska Institutet; National Cancer Institute; Maastricht University; Mahidol University; Norwegian Institute of Public Health; University of Queensland; Roswell Park Cancer Institute; Royal College of General Practitioners Oral Contraception Study; Curtin University; University of Massachusetts System; Boston University; Stanford University; University of Athens Medical School; Universidad de Chile; University of Hawaii System; Skånes universitetssjukhus; University of Pittsburgh; University of Pennsylvania; University Medical Center Utrecht; University of Southern California; Universitetet i Tromso; Vanderbilt University; Organisation Mondiale de la Sante; Yale University
    Background: Oral contraceptives were introduced almost 50 years ago, and over 100 million women currently use them. Oral contraceptives can reduce the risk of ovarian cancer, but the eventual public-health effects of this reduction will depend on how long the protection lasts after use ceases. We aimed to assess these effects. Methods: Individual data for 23 257 women with ovarian cancer (cases) and 87 303 without ovarian cancer (controls) from 45 epidemiological studies in 21 countries were checked and analysed centrally. The relative risk of ovarian cancer in relation to oral contraceptive use was estimated, stratifying by study, age, parity, and hysterectomy. Findings: Overall 7308 (31%) cases and 32 717 (37%) controls had ever used oral contraceptives, for average durations among users of 4·4 and 5·0 years, respectively. The median year of cancer diagnosis was 1993, when cases were aged an average of 56 years. The longer that women had used oral contraceptives, the greater the reduction in ovarian cancer risk (p<0·0001). This reduction in risk persisted for more than 30 years after oral contraceptive use had ceased but became somewhat attenuated over time-the proportional risk reductions per 5 years of use were 29% (95% CI 23-34%) for use that had ceased less than 10 years previously, 19% (14-24%) for use that had ceased 10-19 years previously, and 15% (9-21%) for use that had ceased 20-29 years previously. Use during the 1960s, 1970s, and 1980s was associated with similar proportional risk reductions, although typical oestrogen doses in the 1960s were more than double those in the 1980s. The incidence of mucinous tumours (12% of the total) seemed little affected by oral contraceptives, but otherwise the proportional risk reduction did not vary much between different histological types. In high-income countries, 10 years use of oral contraceptives was estimated to reduce ovarian cancer incidence before age 75 from 1·2 to 0·8 per 100 users and mortality from 0·7 to 0·5 per 100; for every 5000 woman-years of use, about two ovarian cancers and one death from the disease before age 75 are prevented. Interpretation: Use of oral contraceptives confers long-term protection against ovarian cancer. These findings suggest that oral contraceptives have already prevented some 200 000 ovarian cancers and 100 000 deaths from the disease, and that over the next few decades the number of cancers prevented will rise to at least 30 000 per year. © 2008 Elsevier Ltd. All rights reserved.
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    Ovarian cancer and smoking: Individual participant meta-analysis including 28 114 women with ovarian cancer from 51 epidemiological studies
    (2012-01-01) E. E. Calle; S. M. Gapstur; A. V. Patel; L. Dal Maso; R. Talamini; A. Chetrit; G. Hirsh-Yechezkel; F. Lubin; S. Sadetzki; E. Banks; V. Beral; D. Bull; K. Callaghan; B. Crossley; K. Gaitskell; A. Goodill; J. Green; C. Hermon; T. Key; K. Moser; G. Reeves; F. Sitas; R. Collins; R. Doll; R. Peto; C. A. Gonzalez; N. Lee; P. Marchbanks; H. W. Ory; H. B. Peterson; P. A. Wingo; N. Martin; T. Pardthaisong; S. Silpisornkosol; C. Theetranont; B. Boosiri; S. Chutivongse; P. Jimakorn; P. Virutamasen; C. Wongsrichanalai; A. Tjonneland; L. Titus-Ernstoff; T. Byers; T. Rohan; B. J. Mosgaard; M. Vessey; D. Yeates; J. L. Freudenheim; J. Chang-Claude; R. Kaaks; K. E. Anderson; A. Folsom; K. Robien; J. Hampton; P. A. Newcomb; M. A. Rossing; D. B. Thomas; N. S. Weiss; E. Riboli; F. Clavel-Chapelon; D. Cramer; S. E. Hankinson; S. S. Tworoger; S. Franceschi; C. La Vecchia; E. Negri; H. O. Adami; C. Magnusson; T. Riman; E. Weiderpass; A. Wolk; L. J. Schouten; P. A. van den Brandt; N. Chantarakul; S. Koetsawang; D. Rachawat; D. Palli; A. Black; L. A. Brinton; D. M. Freedman; P. Hartge; A. W. Hsing; Jr V. Lacey; R. N. Hoover; C. Schairer; M. Urban; S. Graff-Iversen; R. Selmer; C. J. Bain; A. C. Green; D. M. Purdie; V. Siskind; P. M. Webb; K. Moysich; S. E. McCann; P. Hannaford; C. Kay; C. W. Binns; A. H. Lee; M. Zhang; American Cancer Society; IRCCS Centro Di Riferimento Oncologico Aviano; The Gertner Institute; The National Israeli Study on Ovarian Cancer (NISOC) group; Cancer Council New South Wales; Cancer Research UK; Institute Catala Oncologia; Centers for Disease Control and Prevention; Chiang Mai University; Chulalongkorn University; Institute of Cancer Epidemiology - Denmark; Geisel School of Medicine at Dartmouth; Colorado School of Public Health; Albert Einstein College of Medicine of Yeshiva University; Amtssygehuset i Herlev; Department of Public Health; University at Buffalo, State University of New York; German Cancer Research Center; University of Minnesota School of Public Health; University of Washington, Seattle; Imperial College London; Centre de recherche en epidemiologie et sante des populations; Harvard Medical School; International Agency for Research on Cancer; Universita degli Studi di Milano; Karolinska Institutet; Maastricht University; Mahidol University; Centro Per Lo Studio E La Prevenzione Oncologica; National Cancer Institute; National Health Laboratory Services; Norwegian Institute of Public Health; Queensland Institute of Medical Research; Roswell Park Cancer Institute; Royal College of General Practitioners' Oral Contraception Study; Curtin University; University of Texas School of Public Health; University of Massachusetts Boston; Boston University - Slone Epidemiology Unit; Stanford University; University of Athens Medical School; Universidad de Chile; University of Hawaii at Manoa; Skånes universitetssjukhus; University of Pennsylvania; University of Pittsburgh; University Medical Center Utrecht; University of Southern California; University of Toronto; Universitetet i Tromso; George Washington University; Vanderbilt University; Organisation Mondiale de la Sante; Yale University
    Background Smoking has been linked to mucinous ovarian cancer, but its eff ects on other ovarian cancer subtypes and on overall ovarian cancer risk are unclear, and the fi ndings from most studies with relevant data are unpublished. To assess these associations, we review the published and unpublished evidence. Methods Eligible epidemiological studies were identifi ed by electronic searches, review articles, and discussions with colleagues. Individual participant data for 28 114 women with and 94 942 without ovarian cancer from 51 epidemiological studies were analysed centrally, yielding adjusted relative risks (RRs) of ovarian cancer in smokers compared with never smokers. Findings After exclusion of studies with hospital controls, in which smoking could have aff ected recruitment, overall ovarian cancer incidence was only slightly increased in current smokers compared with women who had never smoked (RR 1.06, 95% CI 1.01-1.11, p=0.01). Of 17 641 epithelial cancers with specifi ed histology, 2314 (13%) were mucinous, 2360 (13%) endo metrioid, 969 (5%) clear-cell, and 9086 (52%) serous. Smoking-related risks varied substantially across these subtypes (p heterogeneity < 0.0001). For mucinous cancers, incidence was increased in current versus never smokers (1.79, 95% CI 1.60-2.00, p < 0.0001), but the increase was mainly in borderline malignant rather than in fully malignant tumours (2.25, 95% CI 1.91-2.65 vs 1.49, 1.28-1.73; p heterogeneity =0.01; almost half the mucinous tumours were only borderline malignant). Both endometrioid (0.81, 95% CI 0.72-0.92, p=0.001) and clear-cell ovarian cancer risks (0.80, 95% CI 0.65-0.97, p=0.03) were reduced in current smokers, and there was no signifi cant association for serous ovarian cancers (0.99, 95% CI 0.93-1.06, p=0.8). These associations did not vary signifi cantly by 13 sociodemographic and personal characteristics of women including their body-mass index, parity, and use of alcohol, oral contraceptives, and menopausal hormone therapy. Interpretation The excess of mucinous ovarian cancers in smokers, which is mainly of tumours of borderline malignancy, is roughly counterbalanced by the defi cit of endometrioid and clear-cell ovarian cancers. The substantial variation in smoking-related risks by tumour subtype is important for understanding ovarian carcinogenesis.
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    TBK-1 Promotes Autophagy-Mediated Antimicrobial Defense by Controlling Autophagosome Maturation
    (2012-08-24) Manohar Pilli; John Arko-Mensah; Marisa Ponpuak; Esteban Roberts; Sharon Master; Michael A. Mandell; Nicolas Dupont; Wojciech Ornatowski; Shanya Jiang; Steven B. Bradfute; Jack Ansgar Bruun; Tom Egil Hansen; Terje Johansen; Vojo Deretic; University of New Mexico Health Sciences Center; Mahidol University; Universitetet i Tromso
    Autophagy is a fundamental biological process of the eukaryotic cell contributing to diverse cellular and physiological functions including cell-autonomous defense against intracellular pathogens. Here, we screened the Rab family of membrane trafficking regulators for effects on autophagic elimination of Mycobacterium tuberculosis var. bovis BCG and found that Rab8b and its downstream interacting partner, innate immunity regulator TBK-1, are required for autophagic elimination of mycobacteria in macrophages. TBK-1 was necessary for autophagic maturation. TBK-1 coordinated assembly and function of the autophagic machinery and phosphorylated the autophagic adaptor p62 (sequestosome 1) on Ser-403, a residue essential for its role in autophagic clearance. A key proinflammatory cytokine, IL-1β, induced autophagy leading to autophagic killing of mycobacteria in macrophages, and this IL-1β activity was dependent on TBK-1. Thus, TBK-1 is a key regulator of immunological autophagy and is responsible for the maturation of autophagosomes into lytic bactericidal organelles. © 2012 Elsevier Inc.