Aristolochic acid and the risk of female lung cancer: Population-based case-control study in Taiwan

Aristolochic acid (AA) is a known human carcinogen that induces DNA adducts and lung tumors in rodents exposed to it. SBS22a, linked to aristolochic acid, appeared almost exclusively in Taiwanese never-smoking lung cancer patients. As there are relatively few female smokers in Taiwan, the objective of this study is to examine the potential risk of lung cancer in women who consume herbs containing AA.

A case-control study based on the population was conducted, where cases were individuals newly diagnosed with lung cancer (ICD-9 162) between January 1, 1999, and December 31, 2013. Logistic regression was utilized to evaluate the risk of lung cancer in relation to the total dose of AA-containing herbs and the estimated cumulative dose of AA.

Women who used Chinese herbal products containing aristolochic acid (AA) had a slightly increased risk of lung cancer compared with non-users (adjusted OR: 1.08; 95% CI: 1.04-1.12). Increased risks were observed across several duration-of-use categories, with a significant trend for duration of estimated AA exposure. However, no clear dose-response relationship was identified for individual AA-containing herbs or estimated cumulative AA dose. Several comorbidities and medications, including chronic obstructive pulmonary disease, tuberculosis, pneumococcal pneumonia, human papillomavirus infection, alcohol-related disease, hyperlipidemia, hormone replacement therapy, and non-steroidal anti-inflammatory drug use, were also associated with increased lung cancer risk.

The study found that consumption of herbs containing aristolochic acid was associated with a modestly increased risk of lung cancer in women. However, the observed association was small, and no clear dose-response relationship was identified. Therefore, the findings should be interpreted cautiously given the potential for residual confounding and limitations in exposure assessment.

In a low-smoking population where the aristolochic acid-associated mutational signature (SBS22a) has been observed predominantly in Taiwanese never-smokers, this nationwide case-control study suggests a possible association between AA-containing herbal products and lung cancer risk in women. Further studies with improved exposure characterization and molecular validation are needed to clarify the role of AA exposure in lung carcinogenesis.