Tuesday, January 24, 2017

Federal Studies: ZERO Mouth Cancer Deaths Among Men Who Dip or Chew Tobacco

The U.S. Food & Drug Administration (FDA) on January 23, 2017 published a proposed smokeless tobacco (ST) regulation (here) that is based on erroneous calculations of ST risks.

The agency would require a radical reduction in N-nitrosonornicotine (NNN), a tobacco-specific nitrosamine, in smokeless tobacco (ST) products.  Most American ST products today have very low NNN levels: about 2-10 millionths of a gram per gram of product – that is, 2-10 parts per million (ppm), while a limited number of products contain 10-15 ppm (here).  The FDA proposes to limit the NNN level in ST products to one ppm or lower. 

As is typical with FDA action on ST (here and here), this proposal is based on obscure calculations and flawed assumptions and interpretation.  Here is a summary of the FDA logic:

  • Compared with never users, ST users have an excess risk of mouth and throat cancer (Relative risk, RR = 2.16). 

  • ST use causes 276 deaths from mouth and throat cancer in the U.S. each year (this number was rounded to 300 in the proposed rule) – 268 men and 8 women. 

  • ST products contain NNN, a human carcinogen that causes mouth and throat cancer. 

  • Reducing NNN levels to no more than 1 ppm will reduce the number of deaths by about 115 per year.

While the latter two statements are by no means scientific certainties, in this post I will focus on the demonstrably inaccurate first assertion, which is the flawed basis for the FDA’s calculation of “300” deaths due to ST use.

The FDA’s use of an RR of 2.16 is in error. The figure, based on a 2008 report (abstract here), combines radically different RRs for men and women.  In 2002, I documented (here) that men, who generally use moist snuff (also called dip) or chew, do not have significantly elevated risk for mouth and throat cancer (RR ~ 1).  In contrast, women, who primarily use powdered dry snuff, have significantly elevated risk (RR ~ 4-6). 

My research is in general agreement with risk estimates published last year by the National Institute of Environmental Health Sciences’ Annah Wyss and colleagues at the National Cancer Institute and over a dozen universities and health centers in the U.S. and beyond (abstract here).  They determined odds ratios (ORs, interpreted the same as RRs) among snuff and chew users for head and neck cancer – which includes voicebox cancer in addition to mouth and throat, but the risk estimates are applicable.  The combined OR among snuff users, men and women combined, was 1.71, which is similar to the FDA estimate.  However, the OR among men was 0.86, while the OR among women was 8.89.  The ORs for chewing tobacco were not significantly elevated for men or women. 

I will use the Wyss ORs to show how the application of risks specific to men and women change the FDA estimates.  First, the following table (adapted from Table 5 in the FDA’s proposed rule) summarizes the data the FDA used (ST prevalence, RRs and total numbers of deaths from mouth-throat cancer in the U.S.) and the agency’s estimates for deaths attributable to ST (last column).  The FDA erred in applying a single RR (2.16) for men and women when, in fact the RR is 0.86 for men and 8.89 for women.

Table 1. FDA Estimate of Annual Deaths from Mouth and Throat Cancer Attributable to Smokeless Tobacco (ST), Men and Women in the U.S.
Prevalence of ST Use (%)Relative RiskAll Mouth/Throat Cancer DeathsPercentage Attributable to STNumber Attributable to ST
Age 35-64 years4.62.162,7705.1140
Age 65+ years3.92.162,9974.3128
Age 35-64 years0.22.168320.32
Age 65+ years0.32.161,6990.36

In the next table I illustrate how the death estimates change if the specific ORs for men (0.86) and women (8.89) from the Wyss study are used. 

Table 2. Revised Estimate of Annual Deaths from Mouth and Throat Cancer Attributable to Snuff Use, Men and Women in the U.S.
Prevalence of ST Use (%)Relative RiskAll Mouth/Throat Cancer DeathsPercentage Attributable to STNumber Attributable to ST
Age 35-64 years4.60.862,77000
Age 65+ years3.90.862,99700
Age 35-64 years0.28.898321.5613
Age 65+ years0.38.891,6992.3139

As noted earlier, my revised estimates are specific to snuff use – powdered dry snuff for women and moist snuff for men.  However, the risks for chewing tobacco in the Wyss study are not significantly elevated for men or women, so that product would add zero deaths. 

In summary, the FDA failed to use RRs specific to men and women, resulting in overestimation of cancer deaths in the former and underestimation in the latter.  Using the same FDA formula and assigning the proper risks, I estimate that 52 women using powdered dry snuff die each year from mouth-throat cancer, but the number of deaths among men who use dip or chew is zero.  The proposed regulation is therefore unjustified for dip and chew products.


mike said...

If it were going to regulate the manufacturing of ST and potentially make it safer by lowing the amount of carcinogenic exposure, what is the issue with it? Just my opinion but it seems silly to not make it even safer especially because you advocating its use over smoking.

Brad Rodu said...


Your view is that the proposed FDA rule will make ST products "even safer." However, the FDA used invalid risk estimates to calculate the number of annual deaths in the U.S. from using dip (moist snuff) and chew (loose leaf chewing tobacco), and the number of deaths avoided by the proposed rule. Decades of epidemiologic research document that these products have little to no measurable risk for mouth and throat cancer. Therefore, the proposed regulation is therefore unjustified for dip and chew products.

mike said...

I don't disagree with you at all, after all you are a doctor :). I was simply stating that if it could be made safer why not? We know that the aforementioned chemicals in ST are carcinogenic so why not eliminate more of them. I have searched high and low and cannot find much information on other cancers it may contribute too ie. Stomach, pancreatic, etc. Maybe it doesn't at all, but it's tough to decipher truths especially when the governement and large organizations use data and coincidence to state facts.

Brad Rodu said...


There are numerous carcinogens in roasted coffee. Why not eliminate them? See my blog post (http://rodutobaccotruth.blogspot.com/2011/11/carcinogens-in-coffee-and-smokeless.html ) on the comparison of coffee and smokeless tobacco.

Eric Falkenstein said...

It's interesting how being a ST user allows insurance to charge the 'smoker rate' for life insurance, etc. I have a sense that insurance companies are highly constrained in what activities they can actually use, and so are happy to use whatever they are allowed. Getting rid of that would make them raise rates across everyone else. The fact that smokeless tobacco users are generally white males, makes them a very attractive target group.