Mutagen sensitivity, tobacco smoking and breast cancer risk: a case-control study.
Given the high incidence of breast cancer and that more than half of cases remain unexplained, the need to identify risk factors for breast cancer remains. Deficiencies in DNA repair capacity have been associated with cancer risk. The mutagen sensitivity assay (MSA), a phenotypic marker of DNA damage response and repair capacity, has been consistently shown to associate with the risk of tobacco-related cancers.


METHODS
In a case-control study of 164 women with breast cancer and 165 women without the disease, we investigated the association between mutagen sensitivity and risk of breast cancer using bleomycin as the mutagen.


RESULTS
High bleomycin sensitivity (>0.65 breaks per cell) was associated with an increased risk of breast cancer, with an adjusted odds ratio of 2.8 [95% confidence interval (CI) = 1.7-4.5]. Risk increased with greater number of bleomycin-induced chromosomal breaks (P(trend) = 0.01). The association between bleomycin sensitivity and breast cancer risk was greater for women who were black, premenopausal and ever smokers. Our data also suggest that bleomycin sensitivity may modulate the effect of tobacco smoking on breast cancer risk. Among women with hypersensitivity to bleomycin, ever smokers had a 1.6-fold increased risk of breast cancer (95% CI = 0.6-3.9, P for interaction between tobacco smoking and bleomycin sensitivity = 0.32).


CONCLUSIONS
Increased bleomycin sensitivity is significantly associated with an increased risk of breast cancer in both pre- and postmenopausal women. Our observation that the effect of tobacco smoking on breast cancer risk may differ based on mutagen sensitivity status warrants further investigation.
Kosti
Ourania
O
Department of Oncology, Carcinogenesis, Biomarkers and Epidemiology Program, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057, USA.
Byrne
Celia
C
Meeker
Katherine L
KL
Watkins
Kenshata M
KM
Loffredo
Christopher A
CA
Shields
Peter G
PG
Schwartz
Marc D
MD
Willey
Shawna C
SC
Cocilovo
Costanza
C
Zheng
Yun-Ling
YL
D000328:Adult; D000368:Aged; D001761:Bleomycin / Q000633:toxicity*; D001943:Breast Neoplasms / Q000209:etiology*; D016022:Case-Control Studies; D004260:DNA Repair; D015914:Estrogen Replacement Therapy / Q000009:adverse effects; D005260:Female; D006801:Humans; D016015:Logistic Models; D008593:Menopause; D008875:Middle Aged; D009153:Mutagens / Q000633:toxicity*; D016017:Odds Ratio; D012306:Risk; D012907:Smoking / Q000009:adverse effects*
D009153:Mutagens; D001761:Bleomycin