NNAL (Cancer pee?)

There are a number of tobacco-associated compounds that are formed by reactions of nicotine. Cotinine is a metabolite formed from nicotine in the body - it hangs around a relatively long time, so it is a good marker for recent nicotine exposure.

Additionally, a number of nitrosamines, formed during tobacco processing, are present - many formed from nicotine. Nitrosamines are pretty nasty - just about any compound of this class is regarded as a suspect carcinogen. Nitrosamines are responsible for a lot of the bad rap cured meat gets for its role in colon cancer risk. These nicotine-derived nitrosamines have attracted similar attention for their potential causative role in tobacco-associated cancers.

NNAL is a metabolite of one of these tobacco-processing associated nitrosamines. This week, Jian-Min Yuan and colleagues presented some results demonstrating a positive correlation between NNAL and cotinine levels in urine and the later occurence of cancer.

Interestingly, it looks like brand makes a difference:

Our results reveal that urinary total NNAL levels were more than 4-fold higher among smokers in Singapore than in Shanghai. One might wonder if the lower levels of total NNAL in Shanghai versus Singapore smokers were the result of degradation of NNAL in urine during storage. Shanghai samples were collected during 1986-1989 while the Singapore samples were collected during 1994-2005. We believe this is an unlikely scenario. Our experimental data have shown that total NNAL is stable for at least 4 years in urine samples stored at -20 °C. Further, mean total NNAL (0.74 pmol/mg Cr) based on samples collected during the early phase of the Singapore Study (1994-1999) was comparable to that (0.65 pmol/mg Cr) based on samples collected later (2000-2005) (P = 0.70). We speculate that the varying levels of urinary total NNAL between smokers in Shanghai versus Singapore may stem from the considerably lower concentrations of NNK in local Chinese brands (western, imported brands were unavailable in Shanghai during 1986-1989 when subjects were recruited into the cohort) relative to the western brands used by most smokers in Singapore.

There are companies out there developing low-nitrosamine tobacco curing methods, like Star Scientific (disclosure: no position). However, they take some flak in the press - regulators and physicians tend to dislike anything that smells like a "safe cigarette" claim. Studies like the present one are a pretty good argument for harm reduction strategies like nitrosamine reduction, though. Good article on them here.