Risk factors for trisomy 21: maternal cigarette smoking and oral contraceptive use in a population-based case-control study

Genetics in Medicine : Official Journal of the American College of Medical Genetics
Q YangS B Freeman

Abstract

We examined maternal smoking and oral contraceptive use as possible risk factors in the genesis of cases of trisomy 21 of maternal origin. This is the first epidemiological study to categorize cases of trisomy 21 by parent of origin and timing of the meiotic error before assessing possible risk factors. We used chromosome 21-specific DNA markers to assign origin to each case. Structured interviews were employed to determine maternal smoking and oral contraceptive use around conception. The odds ratio (OR) for maternal smoking was significantly increased among younger mothers (OR = 2.98; 95% CI = 1.01-8.87), but only in a particular subset of meiotically-derived cases. The combined use of cigarettes and oral contraceptives increased the risk further (OR = 7.62; 95% CI = 1.63-35.6); however, oral contraceptive use alone was not a significant risk factor. Our results indicate that categorizing cases of trisomy 21 by parent and timing of the meiotic error allows more precision in identifying risk factors and may shed light on mechanisms of meiotic nondisjunction.

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