Association of Asbestos Exposure With Malignant Mesothelioma Incidence in Eastern China

The reported incidence of malignant mesothelioma (MM) in China is 1.5 cases per million population, much lower than in other countries.¹ In China, the prevalence of MM in different regions is unknown,¹ and only 15% of MMs have been associated with asbestos exposure^1,2 compared with more than 70% in most of the world.^3,4

We reviewed all pleural and peritoneal malignant tumors diagnosed as MM from January 1, 2002, through December 31, 2015, in the Zhejiang Cancer Hospital (ZJCH), which is the largest cancer hospital in Hangzhou, China, and where there is no asbestos industry, and in the nearby (112 km) Yuyao People’s Hospital, Yuyao, China, located in the Chinese textile asbestos industrial area, where most patients are exposed to asbestos. We reviewed a total of 92 MMs: 34 in the pleura, 56 in the peritoneum, and 2 in the tunica vaginalis.

Asbestos exposure was determined by a trained oncologist (W.M., Z. Guo, or Z. Gao) who interviewed patients for occupational and family histories. Individuals who worked in trades in which asbestos exposure was likely or who grew up or lived in families in which others were employed in the textile industry or trades associated with asbestos were identified as being exposed to asbestos. This retrospective study was approved by the Zhejiang Cancer Hospital Ethical Committee and the Zhejiang Academy of Medical Sciences Ethical Committee. We obtained formalin-fixed, paraffin-embedded tissues from blocks kept in Department of Pathology, Zhejiang Cancer Hospital, and Yuyao Hospital. Patient information was obtained through medical records and patient and family interview. All patients provided verbal informed consent, and data were not deidentified.

Reviewing histologic findings with the aid of a large immunohistochemical panel, we confirmed the diagnosis of MM in 28 patients from ZJCH and 24 from Yuyao People’s Hospital (52 of 92 cases [57%]). The male to female ratio was approximately 1:4 (19%; 95% CI, 10%-32%) compared with 4:1 (80%) in the United States (z = 11.0, P < .001). The pleural to peritoneal MM ratio was approximately 1:3 (24%; 95% CI, 13%-38%) compared with 5:1 (83%) in the United States (z = 11.2, P < .001). The mean (SD) age at diagnosis was 50.6 (7.9) years (95% CI, 48.4-52.7 years) compared with 72 (9.5) years in the United States (t₅₁ = 19.3, P < .001). Twenty of the 52 MMs (5 in the pleura, 14 in the peritoneum, and 1 in the tunica vaginalis) occurred in asbestos-exposed individuals (38%; 95% CI, 25%-53%): 2 of 28 (7%; 95% CI, 1%-23%) at the ZJCH and 18 of 24 (75%; 95% CI, 53%-90%) at Yuyao People’s Hospital. Computed tomograms available for 16 of 28 MMs found at the ZJCH supported asbestos exposure in 2 of 16 cases (13%; 95% CI, 2%-38%). Asbestos-related MMs occurred in 19 women and 1 man. Nine of 52 MMs (17%; 95% CI, 8%-30%) occurred in individuals 40 years or younger compared with less than 1% in the same age group in the United States³ (Table 1 and Table 2).

The higher prevalence of peritoneal vs pleural MMs in China, especially among nonexposed young women, is unique.^3,4,6 Initially we thought that asbestos was the main cause because 13 of 18 peritoneal MMs (72%; 95% CI, 46%-90%) from Yuyao People’s Hospital occurred in women exposed to asbestos. However, only 1 of 14 peritoneal MMs (7%; 95% CI, 0%-34%) from the ZJCH was associated with asbestos. Except for asbestos exposure, no significant demographic differences were observed between the ZJCH and Yuyao People’s Hospital (Table 1 and Table 2), suggesting that asbestos may not be the main cause of MM in these women. These findings point to a unique opportunity to investigate other causes of peritoneal MMs in this population, aside from asbestos. In the United States and Europe, an increasing number of peritoneal MMs do not seem to be associated with asbestos,⁵ leading some authors to speculate that a subgroup of peritoneal MMs may have a different pathogenesis.^3,6

In most industrialized countries, pleural MMs characteristically occur in a setting of asbestos exposure.^3,6 Because men are most often involved in asbestos trades, the incidence of pleural MMs is higher in men, with a male to female ratio of approximately 4:1.^3,6 Instead, among Chinese patients with 12 pleural MMs, 10 of 12 were women (83%; 95% CI, 52%-99%) and only 5 of 12 (42%; 95% CI, 15%-72%) had been exposed to asbestos, underscoring the unusual prevalence of MM in Chinese women (Table 1).

Corresponding Author: Michele Carbone, MD, PhD, Thoracic Oncology Program, University of Hawaii Cancer Center, 701 Ilalo St, Room 437, Honolulu HI 96813 (mcarbone@cc.hawaii.edu).

Correction: This article was corrected for clarification of conflict of interest disclosures on February 9, 2017.

Accepted for Publication: October 7, 2016.

Published Online: December 1, 2016. doi:10.1001/jamaoncol.2016.5487

Author Contributions: Drs Mao, Zhang, and Carbone contributed equally to this work. Drs Mao and Zhang had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Mao, Zhang, Guo, Pass, Yang, Carbone.

Acquisition, analysis, or interpretation of data: Mao, Zhang, Guo, Gao, Pass, Carbone.

Drafting of the manuscript: Mao, Zhang, Guo, Pass, Carbone.

Critical revision of the manuscript for important intellectual content: Mao, Guo, Gao, Pass, Yang, Carbone.

Obtained funding: Mao, Zhang.

Administrative, technical, or material support: Mao, Zhang, Guo, Pass, Yang.

Study supervision: Mao, Zhang, Gao, Carbone.

Conflict of Interest Disclosures: Dr Yang reported receiving grants R01CA160715 from the National Cancer institute, CA120355 from the US Department of Defense, and funding from the V-Foundation and Shino Test Corporation. Drs Yang and Carbone reported having a pending patent application on high mobility group box 1 (HMGB1) and its isoforms and a patent on total HMGB1 issued. Dr Pass reported having a patent on fibulin pending, a patent for osteopontin issued, and a patent on HMGB1 issued (together with Drs Yang and Carbone) as biomarkers for mesothelioma. Dr Carbone reported having pending patent applications on BRCA1 associated protein 1 (BAP1) and providing consultation for mesothelioma expertise and diagnosis at no cost to patients and colleagues and for a fee to lawyers. Dr Carbone also reported receiving grants from the V-Foundation; receiving support from the University of Hawaii Foundation, which received generous donations from Honeywell International Inc to support his mesothelioma research; and receiving support from the Riviera United 4-a Cure to support mesothelioma research conducted by him and Dr Yang. Payment from lawyers representing both sides of litigation was related to review of cases of patients with pleural tumors and the diagnosis of mesothelioma and for expert testimony, the last of which was provided in 2014. No other disclosures were reported.

Funding/Support: This study was supported by grant 81672315 from the National Natural Science Foundation of China (Dr Mao), grant LY16H160036 from the Zhejiang Provincial Natural Science Foundation of China (Dr Guo), and grants P30 CA071789-13 and 1R01CA198138-01 from the National Cancer Institute (Dr Carbone).

Role of the Funder/Sponsor: The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.