Damage to DNA in cervical epithelium related to smoking tobacco

Abstract

Objective - To determine whether tobacco smoking causes increased DNA modification (adducts) in human cervical epithelium. Design - Comparison of DNA adducts measured by the technique of postlabelling with phosphorus-32 in normal ectocervical epithelium of smokers and non-smokers. A questionnaire on smoking habit and a urinary cotinine assay were used to identify smokers and non-smokers. Setting - Cytology unit in large teaching hospital. Subjects - 39 women (11 current smokers, seven former smokers, and 21 who had never smoked) undergoing gynaecological treatment (colposcopy or hysterectomy). Nineteen members of staff who did not smoke as controls. Interventions - Biopsy of normal ectocervical epithelium. Urine sample. Main outcome measures - Measurement of DNA adducts in cervical epithelial tissue of smokers and non-smokers. Smoking habit derived from results of questionnaire and urinary cotinine:creatinine ratio. Proportion of adducts in women with abnormal and normal results of cervical smear test. Results - DNA samples from smokers (identified from questionnaire) had significantly higher median proportions of DNA adducts that non-smokers (4-62 (95% confidence interval 4·04 to 7·74) v 3·47 (2·84 to 4·78) adducts/108 nucleotides; p=0·048). Exclusion of women whose urinary cotinine;creatinine ratio did not confirm their self reported smoking habit (smoker or non-smoker) increased this difference (4·7 (3·85 to 8·08) v 3·52 (2·32 to 4·95) adducts/108 nucleotides; p=0·03). Women who had abnormal results of cervical smear tests had significantly higher proportions of adducts than those with normal results (4·7 (3·90 to 8·13) v 3·47 (3·06 to 5·36) adducts/108 nucleotides; p=0·03). Conclusions - Tobacco smoking by women leads to increased modification of DNA in cervical epithelium, suggesting biochemical evidence consistent with smoking as a cause of cervical cancer.