Research Article Exposure to Diagnostic Radiological Procedures and the Risk of Childhood Acute Lymphoblastic Leukemia Helen D. Bailey 1 , Bruce K. Armstrong 2 , Nicholas H. de Klerk 1 , Lin Fritschi 3 , John Attia 4,5 , Liane Lockwood 6 , and Elizabeth Milne 1 ; for the Aus-ALL Consortium Abstract Background: Diagnostic irradiation of the mother during pregnancy increases the risk of childhood acute lymphoblastic leukemia (ALL). There is inconsistent evidence on associations between ALL and other parental or childhood diagnostic irradiation. The aim of this analysis is to investigate whether diagnostic X-rays of the mother before birth, of the father before conception, or of the child increased the risk of childhood ALL. Methods: Data from 389 cases and 876 frequency-matched controls were analyzed using unconditional logis- tic regression, adjusting for study matching factors and potential confounders. A meta-analysis of our findings in relation to paternal X-rays before conception with the published findings of previous studies was also conducted. Results: There was no evidence of an increased risk with maternal abdominal X-rays before the birth of the index child or with the child having any X-rays more than 6 months before the censoring date. The odds ratio (OR) for any paternal abdominal X-ray before conception was 1.17 [95% confidence interval (95% CI), 0.88-1.55], and 1.47 (95% CI, 0.98-2.21) for more than one X-ray. The OR for any paternal intravenous pyelogram before conception was 3.56 (95% CI, 1.59-7.98). The pooled OR for this study with previous studies of any paternal abdominal X-rays before conception was 1.17 (95% CI, 0.92-1.48). Conclusions: There was some evidence of an increased risk of ALL in the offspring if the father had more than one abdominal X-ray before conception or had ever had an intravenous pyelogram. Impact: We plan to repeat this analysis by using pooled data to improve precision. Cancer Epidemiol Biomarkers Prev; 19(11); 2897–909. ©2010 AACR. Introduction Acute lymphoblastic leukemia (ALL) is the most com- mon type of childhood cancer in developed countries. In Western countries, the age-standardized incidence rates are approximately 30 to 40 per million (1). It is more common in boys, and the majority of cases are diagnosed before the age of 5 years (2). Little is known with any certainty about the causes of ALL, although it is likely that both environmental and genetic factors play a role (3). Because of the early age at onset of ALL, parental exposure before conception, maternal exposure during pregnancy, and exposure of the child to environmental factors could all play a role. Risk of childhood ALL has previously been associated with exposure to diagnostic X-rays. The most studied exposure has been maternal X-rays during pregnancy. In 1956, it was reported that children whose mothers Authors' Affiliations: 1 University of Western Australia, Telethon Institute for Child Health Research, Centre for Child Health Research, Perth, Western Australia, Australia; 2 University of Sydney, Sydney School of Public Health, New South Wales, Australia; 3 University of Western Australia, Western Australian Institute for Medical Research, Perth, Western Australia, Australia; 4 Centre for Clinical Epidemiology and Biostatistics, University of Newcastle, Newcastle, NSW and 5 Department of Medicine, John Hunter Hospital and Hunter Medical Research Institute, New Lambton, NSW, Australia; and 6 Royal Children's Hospital, Brisbane, Queensland, Australia Note: Supplementary data for this article are available at Cancer Epidemi- ology, Biomarkers & Prevention Online (http://cebp.aacrjournals.org/). The Australian Study of Causes of Acute Lymphoblastic Leukaemia in Children Consortium conducted the study, and the Telethon Institute for Child Health Research (TICHR), University of Western Australia, was the coordinating center. Bruce K. Armstrong (Sydney School of Public Health), Elizabeth Milne (TICHR), Frank M. van Bockxmeer (Royal Perth Hospital), Michelle Haber (Children's Cancer Institute Australia), Rodney J. Scott (University of Newcastle), John Attia (University of Newcastle), Murray D. Norris (Children's Cancer Institute Australia), Carol Bower (TICHR), Nicholas H. de Klerk (TICHR), Lin Fritschi (WA Institute for Medical Research), Ursula R. Kees (TICHR), Margaret Miller (Edith Cowan University), and Judith R. Thompson (WA Cancer Registry) were the research investigators. Helen D. Bailey (TICHR) was the project coordinator. The clinical investigators were as follows: Frank Alvaro (John Hunter Hospital, Newcastle), Catherine Cole (Princess Margaret Hospital for Children, Perth), Luciano Dalla Pozza (Children's Hospital at Westmead, Sydney), John Daubenton (Royal Hobart Hospital, Hobart), Peter Downie (Monash Medical Centre, Melbourne), Liane Lockwood (Royal Children's Hospital, Brisbane), Maria Kirby (Women's and Children's Hospital, Adelaide), Glenn Marshall (Sydney Children's Hospital, Sydney), Elizabeth Smibert (Royal Children's Hospital, Melbourne), and Ram Suppiah (previously Mater Children's Hospital, Brisbane). Corresponding Author: Helen Bailey, Telethon Institute for Child Health Research, Centre for Child Health Research, The University of Western Australia, P.O. Box 855, Perth, WA 6872, Australia. Phone: 61-8-9489- 7922; Fax: 61-8-9489-7700. E-mail: helenb@ichr.uwa.edu.au doi: 10.1158/1055-9965.EPI-10-0542 ©2010 American Association for Cancer Research. 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