Oral use of Swedish moist snuff (snus) and risk for cancer of the mouth, lung, and pancreas in male construction workers: a retrospective cohort study

Summary

Background

Although classified as carcinogenic, snuff is used increasingly in several populations. Scandinavian moist snuff (snus) has been proposed as a less harmful alternative to smoking, but precise data on the independent associations of snus use with site-specific cancers are sparse. We aimed to assess the risks for cancer of the oral cavity, lung, and pancreas.

Methods

Detailed information about tobacco smoking and snus use was obtained from 279 897 male Swedish construction workers in 1978–92. Complete follow-up until end of 2004 was accomplished through links with population and health registers. To distinguish possible effects of snus from those of smoking, we focused on 125 576 workers who were reported to be never-smokers at entry. Adjusted relative risks were derived from Cox proportional hazards regression models.

Findings

60 cases of oral, 154 of lung, and 83 of pancreatic cancer were recorded in never-smokers. Snus use was independently associated with increased risk of pancreatic cancer (relative risk for ever-users of snus 2·0; 95% CI 1·2–3·3, compared with never-users of any tobacco), but was unrelated to incidence of oral (0·8, 95% CI 0·4–1·7) and lung cancer (0·8, 0·5–1·3).

Interpretation

Use of Swedish snus should be added to the list of tentative risk factors for pancreatic cancer. We were unable to confirm any excess of oral or lung cancer in snus users.

Introduction

Use of snuff has become increasingly popular in several countries, but Sweden has the highest consumption, predominantly in the form of moist snuff (snus). The habit is especially gaining popularity in adolescents and women.¹ At present, however, the majority of users are men; at least 23% of Swedish men used snus in 2002.²

About 30 carcinogens have been identified in smokeless tobacco, and the tobacco-specific nitrosamines, formed from nicotine and related tobacco alkaloids, are thought to be particularly important.³ The tobacco-specific nitrosamines with the greatest proportions in snuff (4-(nitrosomethylamino)-1-(3-pyridyl)-1-butanone [NNK] and N′-nitrosonornicotine [NNN]), have been implicated in the cause of tobacco-related cancers.4, 5, 6 Comparative studies have generally shown lower concentrations of tobacco-specific nitrosamines in Swedish snus than in American snuff,⁷ leading to a perception that the use of Swedish snus is a suitable alternative to smoking. Indeed, with a few exceptions,8, 9, 10 studies of Scandinavian snus have shown no risk associated with use of this form of tobacco.⁷ The Scandinavian experience differs from that in South Asia¹¹ and elsewhere,12, 13 where smokeless tobacco is an established risk factor for oral cancer. This inconsistency might be attributable to methodological aspects, such as inadequate control for confounding by cigarette smoking and alcohol use, which are strong risk factors for oral cancer.

Because of NNK's specificity for the lung in rodent cancer models,14, 15 lung cancer should be another concern in relation to smokeless tobacco. However, few studies have addressed this risk in human beings. The only study of Scandinavian snus and lung cancer showed a non-significantly decreased risk in snus users,¹⁰ raising questions about residual confounding due to smoking. Epidemiological evidence10, 16, 17, 18 suggests that the use of smokeless tobacco, including Scandinavian snus,¹⁰ might increase the risk of pancreatic cancer, but published data are based on few snus-exposed cases.

With a growing awareness of the health hazards associated with smoking, snus could become increasingly popular,19, 20 and the habit might spread to people who would otherwise refrain from tobacco use. Therefore, valid and precise epidemiological data on health risks associated with use of snus are urgently needed. We consequently did a prospective study in Swedish construction workers, with a high prevalence of exposure to snus, to address the association of snus use with oral, lung, and pancreatic cancer.