Urinary metabolites of 1,3-butadiene, benzene and toluene and colorectal cancer incidence: a clinical case-control study.

BACKGROUND

Workplace exposure to volatile organic compounds (VOCs) has been shown to have a positive association with colorectal cancer (CRC) mortality. Benzene, 1,3-butadiene, and toluene are known carcinogens for other cancers. However, the effect of non-occupational VOC exposures on CRC is unknown.

METHODS

A clinical case-control study was performed. CRC cases were enrolled; controls were those patients seen for routine screening. Participants completed a detailed questionnaire and provided urine samples. Urinary VOC metabolites were measured for metabolites of: benzene metabolites (MU, PPMA, PMA), 1,3-butadiene (DHBMA, MHBMA1, MHBMA3), and toluene (BMA) for 43 CRC Cases and 104 controls. Concentrations were creatinine normalized and dichotomized as high or low. Logistic regression was used to estimate Odds Ratios (ORs) of CRC with 95% Confidence Intervals (CI) comparing high to low exposure adjusted for confounding factors.

RESULTS

High levels of the MHBMA3 had 2.62 (95% CI 1.09, 6.31) times higher odds of having CRC compared to those with low levels after confounding adjustment. The adjusted ORs of CRC were elevated for Benzene PPMA (OR = 2.12 95%CI 0.92, 4.88). The metabolites BMA, MU, PMA, and other metabolites of 1,3-butadiene were not associated with CRC.

CONCLUSIONS

MHBMA3 (a metabolite of 1,3-butadiene) was associated with a higher incidence of CRC independent of smoking and other CRC risk factors. Non-smoking sources of 1,3-butadiene, such as environmental sources, may contribute to increasing CRC incidence. Additional epidemiologic studies are needed to confirm this observation. Further laboratory studies are required to identify potential biologic mechanisms specific to MHBMA3 and colorectal carcinogenesis.