Elevated 4-aminobiphenyl and 2,6-dimethylaniline hemoglobin adducts and increased risk of bladder cancer among lifelong nonsmokers--The Shanghai Bladder Cancer Study.

Abstract

BACKGROUND:

4-Aminobiphenyl (ABP) is an established human bladder carcinogen, with tobacco smoke being a major source of human exposure. Other arylamine compounds, including 2,6-dimethylaniline (2,6-DMA), have been implicated as possible human bladder carcinogens. Hemoglobin adducts of 4-ABP and 2,6-DMA are validated biomarkers of exposure to those compounds in humans.

METHODS:

The Shanghai Bladder Cancer Study enrolled 581 incident bladder cancer cases and 604 population controls. Each participant was solicited for his/her history of tobacco use and other lifestyle factors and donation of blood and urine specimens. Red blood cell lysates were used to quantify both hemoglobin adducts of 4-ABP and 2,6-DMA. Urine samples were used to quantify total cotinine. ORs and 95% confidence intervals (CI) for bladder cancer were estimated using unconditional logistic regression methods.

RESULTS:

Among lifelong nonsmokers, ORs (95% CIs) of bladder cancer for low (below median of positive values) and high versus undetectable levels of 2,6-DMA hemoglobin adducts were 3.87 (1.39-10.75) and 6.90 (3.17-15.02), respectively (Ptrend < 0.001). Similarly, among lifelong nonsmokers, ORs (95% CIs) of bladder cancer for third and fourth versus first/second quartiles of 4-ABP hemoglobin adducts was 1.30 (0.76-2.22) and 2.29 (1.23-4.24), respectively (Ptrend = 0.009). The two associations were independent of each other.

CONCLUSION:

Hemoglobin adducts of 4-ABP and 2,6-DMA were significantly and independently associated with increased bladder cancer risk among lifelong nonsmokers in Shanghai, China.

IMPACT:

The findings of the present study in China with previous data in Los Angeles, California strongly implicate arylamines as potential causal agents of human bladder cancer.

• Authors: Li Tao, Billy W Day, Bibin Hu, Yong-Bing Xiang, Renwei Wang, Mariana C Stern, Manuela Gago-Dominguez, Victoria K Cortessis, David V Conti, David Van Den Berg, Malcolm C Pike, Yu-Tang Gao, Mimi C Yu, Jian-Min Yuan
• Journal: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology (Cancer Epidemiol Biomarkers Prev) Vol. 22 Issue 5 Pg. 937-45 (May 2013) ISSN: 1538-7755 [Electronic] United States
• PMID: 23539508 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Aniline Compounds
• Biomarkers, Tumor
• Hemoglobins
• hemoglobin, 4-aminobiphenyl-
• 2,6-xylidine

Topics

• Aged
• Aniline Compounds (blood)
• Biomarkers, Tumor (blood)
• Case-Control Studies
• Female
• Hemoglobins (metabolism)
• Humans
• Male
• Middle Aged
• Risk Factors
• Smoking (blood, urine)
• Urinary Bladder Neoplasms (blood, urine)