Smokeless tobacco-associated cancers: A systematic review and meta-analysis of Indian studies

Abstract

The International Agency for Research on Cancer (IARC) has concluded that there is sufficient evidence in humans for the carcinogenicity of smokeless tobacco (SLT) for mouth, oesophagus and pancreas, based largely on Western studies. We wanted to confirm this by conducting a systematic review using Indian studies because India faces the biggest brunt of SLT-attributable health effects. A systematic search was conducted for published and unpublished studies. Two authors independently reviewed the studies and extracted data. Summary odds ratio (OR) for each cancer type was calculated using fixed and random effects model. The population attributable fraction (PAF) method was used to calculate the attributable burden of incident cases. A significant association was found for oral - 5.55 (5.07, 6.07), pharyngeal - 2.69 (2.28, 3.17), laryngeal - 2.84 (2.18, 3.70), oesophageal - 3.17 (2.76, 3.63) and stomach - 1.26 (1.00, 1.60) cancers. But in random effects model, laryngeal - 1.79 (0.70, 4.54) and stomach - 1.31 (0.92, 1.87) cancers became non-significantly associated. Gender-wise analysis revealed that women had a higher risk (OR = 12.0 vs. 5.16) of oral but a lower risk (1.9 vs. 4.5) of oesophageal cancer compared with men. For oral cancer, studies that adjusted for smoking, alcohol and other factors reported a significantly lower OR compared with studies that adjusted for smoking only or smoking and alcohol only (3.9 vs. 8.4). The annual number of attributable cases was calculated as 49,192 (PAF = 60%) for mouth, 14,747 (51%) for pharynx, 11,825 (40%) for larynx, 14,780 (35%) for oesophagus and 3,101 (8%) for stomach. What's new? In India, smokeless tobacco use is steadily increasing, raising concerns about its impact on national cancer incidence. Indeed, smokeless tobacco causes several different cancers in humans, some of which arise in sites other than the oral cavity. This study shows that in India a significant proportion of incident cancers of the mouth, pharynx, larynx, esophagus, and stomach can be attributed to smokeless tobacco. Associations were strongest for oral, esophageal, and pharyngeal cancers. The findings reinforce concerns about the carcinogenic effects of smokeless tobacco and could facilitate improvements in smokeless tobacco control in South-East Asia.