Smoking and nasopharyngeal cancer: individual data meta-analysis of six prospective studies on 334 935 men

Jia Huang Lin; Chi Pang Wen; Chao Qiang Jiang; Jian-Min Yuan; Chien Jen Chen; Sai Yin Ho; Wayne Gao; Weisen Zhang; Renwei Wang; Yin-Chu Chien; Lin Xu; Xifeng Wu; Ya Li Jin; Woon-Puay Koh; Wan-Lun Hsu; Feng Zhu; Christopher Wen; Tong Zhu; June Han Lee; Zhi-Ming Mai; Maria Li Lung; Tai-Hing Lam

doi:10.1093/ije/dyab060

Smoking and nasopharyngeal cancer: individual data meta-analysis of six prospective studies on 334 935 men

Int J Epidemiol. 2021 Jul 9;50(3):975-986. doi: 10.1093/ije/dyab060.

Authors

Jia Huang Lin^{1

2

3}, Chi Pang Wen^{4

5}, Chao Qiang Jiang⁶, Jian-Min Yuan^{7

8}, Chien Jen Chen^{9

10}, Sai Yin Ho¹, Wayne Gao¹¹, Weisen Zhang⁶, Renwei Wang⁷, Yin-Chu Chien⁹, Lin Xu^{1

12}, Xifeng Wu¹³, Ya Li Jin⁶, Woon-Puay Koh^{14

15}, Wan-Lun Hsu⁹, Feng Zhu⁶, Christopher Wen¹⁶, Tong Zhu⁶, June Han Lee⁴, Zhi-Ming Mai^{1

2

17}, Maria Li Lung^{2

18}, Tai-Hing Lam^{1

2}

Affiliations

¹ School of Public Health, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong.
² Centre for Nasopharyngeal Carcinoma Research (CNPCR), Research Grants Council Area of Excellence Scheme, University of Hong Kong, Hong Kong.
³ Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing, China.
⁴ Institute of Population Health Sciences, National Health Institutes, Zhunan, Taiwan.
⁵ Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan.
⁶ Guangzhou No.12 Hospital, Guangzhou, China.
⁷ Division of Cancer Control and Population Sciences, UPMC Hillman Cancer Centre, University of Pittsburgh, Pittsburgh, PA, USA.
⁸ Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
⁹ Genomics Research Centre, Academia Sinica, Taipei, Taiwan.
¹⁰ Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
¹¹ Master's Program in Global Health and Development, Taipei Medical University, Taipei, Taiwan.
¹² School of Public Health, Sun Yat-sen University, Guangzhou, China.
¹³ Centre for Biostatistics Bioinformatics and Big Data, School of Public Health, National Institute for Data Science in Health and Medicine, Zhejiang University, Hangzhou, China.
¹⁴ Health Services and Systems Research, Duke-NUS Medical School, Singapore.
¹⁵ Saw Swee Hock School of Public Health, National University of Singapore, Singapore.
¹⁶ Department of Radiology, Long Beach Veterans Administration Hospital, University of California at Irvine, Irvine, CA, USA.
¹⁷ Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
¹⁸ Department of Clinical Oncology and Centre for Cancer Research, University of Hong Kong, Hong Kong.

Abstract

Background: The role of smoking in nasopharyngeal carcinoma (NPC) remains uncertain, especially in endemic regions. We conducted an individual participant data (IPD) meta-analysis of prospective cohort studies to investigate the associations between smoking exposure and risk of NPC.

Methods: We obtained individual participant data of 334 935 male participants from six eligible population-based cohorts in NPC-endemic regions, including two each in Guangzhou and Taiwan, and one each in Hong Kong and Singapore. We used one- and two-stage approaches IPD meta-analysis and Cox proportional hazard models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of NPC for smoking exposure adjusting for age and drinking status.

Results: During 2 961 315 person-years of follow-up, 399 NPC evens were ascertained. Risks of NPC were higher in ever versus never smokers (HRone-stage = 1.32, 95% CI = 1.07-1.63, P = 0.0088; HRtwo-stage = 1.27, 1.01-1.60, 0.04). These positive associations appeared to be stronger in ever smokers who consumed 16+ cigarettes/day (HRone-stage = 1.67, 95% CI = 1.29-2.16, P = 0.0001), and in those who started smoking at age younger than 16 (2.16, 1.33-3.50, 0.0103), with dose-response relationships (P-values for trend = 0.0028 and 0.0103, respectively). Quitting (versus daily smoking) showed a small reduced risk (stopped for 5+ years: HRone-stage = 0.91, 95% CI = 0.60-1.39, P = 0.66; for former smokers: HRtwo-stage = 0.84, 0.61-1.14, 0.26).

Conclusions: This first IPD meta-analysis from six prospective cohorts in endemic regions has provided robust observational evidence that smoking increased NPC risk in men. NPC should be added to the 12-16 cancer sites known to be tobacco-related cancers. Strong tobacco control policies, preventing young individuals from smoking, would reduce NPC risk in endemic regions.

Keywords: Nasopharyngeal carcinoma; cohort study; epidemiology; individual data; meta-analysis; smoking.

Publication types

Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

MeSH terms

Hong Kong / epidemiology
Humans
Male
Nasopharyngeal Carcinoma / epidemiology
Nasopharyngeal Neoplasms* / epidemiology
Observational Studies as Topic
Prospective Studies
Risk Factors
Singapore
Smoking / epidemiology
Taiwan