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Maternal Smoking and Oral Clefts: The Role of Detoxification Pathway Genes

Lie, Rolv T.a,b; Wilcox, Allen J.c; Taylor, Jackc; Gjessing, Håkon K.a,d; Saugstad, Ola Didrike; Aabyholm, Frankf; Vindenes, Halvardg



Lie RT, Wilcox AJ, Taylor J, et al. Maternal smoking and oral clefts: The role of detoxification pathway genes. Epidemiology. 2008;19:606–615.

An error in our triad-data for a small number of control triads for the SNPs NAT2 857, NAT1 1088, and NAT1 1095 caused a minor distortion in our case-control analyses. On page 612, in the second column, lines 15 and 16, the upper confidence limits should be corrected from 1.4 to 1.3 and from 1.9 to 2.0. The P value for test of interaction in line 29 should be corrected from 0.72 to 0.65. Estimates of the effect of NAT1 1088 should be corrected from 1.3 (0.5–3.2) to 1.1 (0.5–2.7) and for NAT1 1095 from 1.3 (0.6–2.7) to 1.2 (0.6–2.5). The errors affect no other analyses and do not alter the conclusions of the paper.

Epidemiology. 21(3):432, May 2010.

doi: 10.1097/EDE.0b013e3181690731
Original Article: BIRTH DEFECTS

Background: There is evidence for an effect of cigarette smoking on risk of oral clefts. There are also hypothetical pathways for a biologic effect involving toxic chemicals in cigarette smoke.

Methods: We performed a combined case-control and family-triad study of babies born with oral clefts in Norway in the period 1996 to 2001, with 88% participation among cases (n = 573) and 76% participation among controls (n = 763). Mothers completed a questionnaire 4 months after birth of the baby. DNA was collected from parents and children, and assayed for genes related to detoxification of compounds of cigarette smoke (NAT1, NAT2, CYP1A1, GSTP1, GSTT1, and GSTM1).

Results: For isolated cleft lip (with or without cleft palate) there was a dose-response effect of smoking in the first trimester. The odds ratio rose from 1.6 (95% confidence interval = 1.0–2.5) for passive smoking to 1.9 (0.9–4.0) for mothers who smoked more than 10 cigarettes per day. There was little evidence of an association with cleft palate. Genetic analyses used both case-control and family-triad data. In case-triads we found an association between a NAT2 haplotype and isolated cleft lip (relative risk of 1.6 with 1 copy of the allele and 2.5 with 2 copies), but with little evidence of interaction with smoking. Other genes did not show associations, and previously described interactions with smoking were not confirmed.

Conclusion: First-trimester smoking was clearly associated with risk of cleft lip. This effect was not modified by variants of genes related to detoxification of compounds of cigarette smoke.

From the aDepartment of Public Health and Primary Health Care, University of Bergen, Norway; bMedical Birth Registry of Norway, Norwegian Institute of Public Health, Bergen, Norway; cEpidemiology Branch, National Institute of Environmental Health Sciences, Durham, NC; dNorwegian Institute of Public Health, Oslo, Norway; eDepartment of Pediatrics, The National Hospital, Oslo, Norway; fDepartment of Plastic Surgery, The National Hospital, Oslo, Norway; and gDepartment of Plastic Surgery, Haukeland Hospital, Bergen, Norway.

Submitted 24 August 2007; accepted 5 December 2007; posted 28 April 2008.

Supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences, The Norwegian Research Council, Helse Vest, and NIH (2RO1 DE-11948-04).

Correspondence: Rolv T. Lie, Department of Public Health and Primary Health Care, University of Bergen, Kalfarveien 31, 5018 Bergen, Norway. E-mail:

© 2008 Lippincott Williams & Wilkins, Inc.