Population-based case-control study of Chinese herbal products containing aristolochic acid and urinary tract cancer risk.
BACKGROUND
Consumption of Chinese herbs that contain aristolochic acid (eg, Mu Tong) has been associated with an increased risk of urinary tract cancer.


METHODS
We conducted a population-based case-control study in Taiwan to examine the association between prescribed Chinese herbal products that contain aristolochic acid and urinary tract cancer. All patients newly diagnosed with urinary tract cancer (case subjects) from January 1, 2001, to December 31, 2002, and a random sample of the entire insured population from January 1, 1997, to December 31, 2002 (control subjects), were selected from the National Health Insurance reimbursement database. Subjects who were ever prescribed more than 500 pills of nonsteroidal anti-inflammatory drugs and/or acetaminophen were excluded, leaving 4594 case patients and 174,701 control subjects in the final analysis. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by using multivariable logistic regression models for the association between prescribed Chinese herbs containing aristolochic acid and the occurrence of urinary tract cancer. Models were adjusted for age, sex, residence in a township where black foot disease was endemic (an indicator of chronic arsenic exposure from drinking water [a risk factor for urinary tract cancer]), and history of chronic urinary tract infection. Statistical tests were two-sided.


RESULTS
Having been prescribed more than 60 g of Mu Tong and an estimated consumption of more than 150 mg of aristolochic acid were independently associated with an increased risk for urinary tract cancer in multivariable analyses (Mu Tong: at 61-100 g, OR = 1.6, 95% CI = 1.3 to 2.1, and at >200 g, OR = 2.1, 95% CI = 1.3 to 3.4; aristolochic acid: at 151-250 mg, OR = 1.4, 95% CI = 1.1 to 1.8, and at >500 mg, OR = 2.0, 95% CI = 1.4 to 2.9). A statistically significant linear dose-response relationship was observed between the prescribed dose of Mu Tong or the estimated cumulative dose of aristolochic acid and the risk of urinary tract cancer (P < .001 for both).


CONCLUSIONS
Consumption of aristolochic acid-containing Chinese herbal products is associated with an increased risk of cancer of the urinary tract in a dose-dependent manner that is independent of arsenic exposure.
Lai
Ming-Nan
MN
Institute of Occupational Medicine and Industrial Hygiene, College of Public Health, National Taiwan University, Room 719, No.17 Xu-Zhou Road, Taipei City 100, Taiwan.
Wang
Shuo-Meng
SM
Chen
Pau-Chung
PC
Chen
Ya-Yin
YY
Wang
Jung-Der
JD
D000328:Adult; D000368:Aged; D034341:Aristolochic Acids / Q000008:administration & dosage* / Q000009:adverse effects*; D002273:Carcinogens; D016022:Case-Control Studies; D015986:Confounding Factors, Epidemiologic; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage* / Q000009:adverse effects*; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D012107:Research Design; D012307:Risk Factors; D013624:Taiwan / Q000453:epidemiology; D014571:Urologic Neoplasms / Q000139:chemically induced* / Q000453:epidemiology
D034341:Aristolochic Acids; D002273:Carcinogens; D004365:Drugs, Chinese Herbal; C000228:aristolochic acid I