More Misinformation About Smokeless Tobacco From the American Cancer Society

American Cancer Society (ACS) investigators have just published results of a study on alcohol consumption and the development of pancreas cancer in the Archives of Internal Medicine (abstract here). Led by Susan M. Gapstur, the study found that, compared with never alcohol drinkers, consumers of three or more drinks per day had an elevated risk of pancreas cancer mortality. The higher risk was statistically significant for never smokers (Relative risk, RR = 1.36, 95% Confidence Interval, CI = 1.13 – 1.62) and for ever smokers (RR = 1.16, CI = 1.06 – 1.27). They did not detect higher risks for beer or wine drinkers, but only for consumption of liquor.

The article discussed the public health implications of the research:

“Alcoholic beverage consumption—a modifiable lifestyle factor—is causally related to several cancers, including oral cavity, pharynx, larynx, esophagus, liver, colorectum, and female breast. Findings from the prospective study presented herein strongly support the hypothesis that alcohol consumption, in particular heavy intake, also is an independent risk factor for pancreatic cancer, the fourth most common cause of cancer mortality in the United States. These results underscore the importance of adhering to the following guideline for cancer prevention by the American Cancer Society: ‘If you drink alcoholic beverages, limit consumption.’”

Thus, while the ACS acknowledges that alcohol is associated with considerable cancer risks, its advice to consumers emphasizes moderation. Historically, moderation has played no role in ACS messages to tobacco users: quit now and abstain completely and permanently.

The ACS web page on smokeless tobacco (available here) was revised on December 16, 2010; it is replete with misinformation, especially about cancer risks. Following are the cancers that the ACS claims, with no supporting data, are caused by smokeless tobacco use, followed by the actual scientific evidence derived from the most comprehensive study ever published (read about it here).

American Cancer Society Claim	Actual Scientific Evidence
Mouth, tongue and throat cancer	Not significantly elevated, RR = 1.07 (CI = 0.84-1.37)
Esophagus cancer	Not significantly elevated, RR = 1.13 (CI = 0.95-1.36)
Stomach cancer	Not significantly elevated, RR = 1.03 (CI = 0.88-1.20)
Pancreatic Cancer	Not significantly elevated, RR = 1.07 (CI = 0.71-1.60)

RR = Relative Risk.

Scientific evidence shows clearly that smokeless tobacco use only slightly elevates cancer risks, if at all. The reported elevations are so small that they are not statistically significant; in other words, they may have occurred purely by chance. It is also important to point out that small RRs (those under 2) should not be seen as reliable. The National Cancer Institute advises: “Relative risks or odds ratios less than 2 are viewed with caution,” because they “are sometimes difficult to interpret.”

Next week I will discuss ACS intransigence with respect to refusing to provide information in its possession about the health risks related to tobacco use.

The Revolving-Door Cohort at the Karolinska Institute

The Karolinska Institute (KI) in Stockholm is Sweden’s premier medical research institution, and among the most well known and respected in the world. For several years a group of researchers in the KI’s Department of Medical Epidemiology and Biostatistics has published numerous studies of the health risks related to snus use.

As I stated in a recent commentary published in Sweden (link here), “the health risks identified in the KI studies are the raison d’être for the ban on snus in the E.U. (except Sweden), but it has also had a profound impact on tobacco regulation in the U.S. and other countries,” making access to snus difficult or impossible.

The KI studies have profoundly influenced regulatory actions all over the world, but they are compromised by important, troubling and unresolved discrepancies that KI researchers have refused to address. This post describes the biggest problem in detail.

The KI studies are based on over 300,000 male Swedish construction workers who enrolled in a health program from 1971 to 1992, including roughly 135,000 workers who were enrolled in the program during the 1971-1974 period. This group is important, because there are potentially serious questions about the adequacy of tobacco use information for these workers. In fact, the information is so questionable that KI researchers have included and excluded them in a revolving door fashion in published analyses over the last several years.

The story goes back to 1994, when KI investigator Gunilla Bolinder and colleagues reported that snus use was a risk factor for cardiovascular diseases. (abstract here). In that study Dr. Bolinder studied only the construction workers from the 1971-74 group (hereafter, the “Bolinder” cohort). That report, one of only a few linking snus use with heart disease and stroke, had some obvious but inexplicable technical problems, which I raised in a 1995 letter to the editor of the journal (here). Dr. Bolinder did not resolve these problems.

Fast-forward 13 years to 2007, when KI investigators Luo et al. published a high profile study in The Lancet finding that snus use was a risk factor for pancreas cancer (here). In their analysis, Luo et al. excluded ALL of the workers in the Bolinder cohort “because of ambiguities in the coding of smoking status” of participants. In other words, Luo tossed out the 135,000 workers of the Bolinder cohort. The justification for these exclusions was an “unpublished” observation by Zendehdel, another KI investigator.

I published a letter to the editor of The Lancet (here) observing that, if the Bolinder cohort was deficient, then the validity of the Bolinder study was suspect. Luo et al. responded that perhaps the exclusions were not warranted (here), citing a KI study that was about to be published. That study, which found that snus use was associated with esophageal and stomach cancer, included the Bolinder cohort (here). The lead author on that study was Zendehdel.

Confusing? Absolutely. First, KI researchers cited Zendehdel as the justification for excluding the Bolinder cohort, but then Zendehdel included the Bolinder cohort in his published study.

To illustrate how many times KI researchers have subjected the Bolinder cohort to revolving door treatment, here is a list of publications.

The Bolinder Revolving Door Cohort At the Karolinska Institute
Year	First Author	Journal	Disease	Bolinder Cohort In/Out
1994	Bolinder	American Journal of Public Health	Cardiovascular	In
2005	Odenbro	British Journal of Cancer	Skin cancer	In
2007	Luo	Lancet	Pancreas cancer	Out
2007	Odenbro	British Journal of Dermatology	Melanoma	In
2007	Fernberg	Cancer Research	Leukemia	In
2007	Hergens	Journal of Internal Medicine	Heart attack	Out
2008	Zendehdel	International Journal of Cancer	Gastrointestinal cancer	In
2008	Hergens	Epidemiology	Stroke	Out
2008	Hergens	Journal of Internal Medicine	Hypertension	Out
2010	Carlens	American Journal of Respiratory and Critical Care Medicine	Inflammatory Diseases	Out
2011	Nordenvall	International Journal of Cancer	Colon-rectal cancer	In

This is unacceptable from a scientific perspective, but there are many other problems. For example, it appears that Dr. Bolinder’s definition of snus use was inconsistent with later definitions. I’ll have more to say about this in a future post.

Snus Users and Smokers in Stockholm

A new study published in Biomed Central Public Health (available here) describes the socioeconomic and lifestyle characteristics of snus users and smokers in Stockholm County, Sweden. Based on a 2006 survey of 35,000 residents, it was authored by Karin Engström and colleagues at the Department of Public Health Sciences at the Karolinska Institute. In addition to providing interesting information about snus users, this study has important implications for Karolinska Institute claims about the link between snus use and cancer.

Among men, 17% were exclusive snus users, 11% smoked and 2.4% were dual users. Among women, cigarette smoking was dominant (15%), while snus use and dual use were only 3.1% and 0.5% respectively. Given this, I will focus on the findings for men.

It is noteworthy that the prevalence of snus use was highest among men less than 35 years old. This means that young men in Stockholm strongly prefer snus, a lifestyle choice that will have little or no effect on their health as they age.

Snus users were somewhat more likely to have lower education levels than nonusers of tobacco, a trend that was even stronger among smokers. Smokers were also more likely to be unskilled and skilled workers in the very low income group, while snus users were more evenly distributed among all occupational classes and across all income levels.

One of the more interesting results concerned alcohol consumption. Risky alcohol consumption was defined as 14 standard drinks per week; the survey also asked about weekly or monthly binge drinking. Snus users and smokers were more likely to practice risky consumption than nonusers (odds ratios = 1.8 – 1.9), and they were more likely to have weekly binge-drinking episodes (ORs around 3.1).

This information on alcohol abuse among snus users is important, because a Karolinska epidemiology group, led by Olof Nyrén, published studies suggesting that snus use is associated with a small risk of pancreatic, stomach and esophageal cancer (abstracts here and here) among workers in the Swedish construction industry. Alcohol abuse is a strong risk factor for esophageal cancer and may be linked to stomach and pancreas cancer; this makes it a confounder with respect to snus use. In other words, if snus users are more likely to be alcohol abusers, then some of the cancers attributed to snus might instead be caused by alcohol. In many modern epidemiologic studies, standard procedures are used to account for confounders. In this case, to accurately separate the risks due to snus use from those due to alcohol abuse.

But the construction worker studies had no information on alcohol consumption, so alcohol abuse could not be ruled out as a competing risk factor. The lack of information about alcohol in these studies is a serious deficiency that raises questions about the validity of Nyrén’s claims.

In summary, men in Stockholm from all income levels and all occupations prefer snus over cigarettes. The impact of this preference on their health is so small that it is barely measurable by modern epidemiologic methods. Furthermore, snus users, like smokers, are more likely to abuse alcohol, which may be a distinct risk factor for some cancers that has not been evaluated in previous Karolinska Institute reports on snus use.