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I didn't downvote, but it definitely does come across as a crackpot screed. You are discounting data in favor of an overly simplistic statistical model. You also greatly misinterpret a key point in the quote: they're not saying all mutations accumulate at a constant rate, but only a few signatures appear to. In fact, the very next sentence of that quote is:

>The absence of consistent correlation of all other signatures with age suggests that mutations associated with these have been generated at different rates in different people, possibly as a consequence of differing carcinogen exposures or after neoplastic change has been initiated.

This is a classic crackpot technique: selectively quote just the parts that you want them to say, twist it a bit further to your needs, then proceed with an overly simplistic, but supposedly impressive analysis. I don't know or really think that you are a crackpot, but the quoting behavior is quite telling.

Getting back to your original comment, you accuse the authors of this paper:

http://science.sciencemag.org/content/354/6312/618.full

of not knowing what they're talking about. But in reality, you have already mistaken the type of process that's being talked about. Stratton is talking about a biological and chemical process. You're talking about a "random" process from statistics. An old theory, that uses simplifying assumptions that do not apply with this data.

And finally, the most obvious reason that the Armitage Doll process is not the best explanation is that AD were looking at the process of carcinogenesis. This paper is looking at the various processes of mutations that happen because of a carcinogen. These are different things, especially since mutational processes accelerate after carcinogenesis. I believe the paragraphs that you would find most interesting from the paper are here:

>Signature 5 is found in all cancer types, including those unrelated to tobacco smoking, and in most cancer samples. It is “clocklike” in that the number of mutations attributable to this signature correlates with age at the time of diagnosis in many cancer types (17). Signature 5, together with signature 1, is thought to contribute to mutation accumulation in most normal somatic cells and in the germline (17, 23). The mechanisms underlying signature 5 are not well understood, although an enrichment of signature 5 mutations was found in bladder cancers harboring inactivating mutations in ERCC2, which encodes a component of NER (24).

>Signature 5 (or a similar signature that is difficult to differentiate from signature 5 because of the relatively flat profiles of these signatures) was increased by a factor of 1.3 to 5.1 (q < 0.05; table S2) in smokers versus nonsmokers in all cancer types together and in lung squamous, lung adenocarcinoma, larynx, pharynx, oral cavity, esophageal squamous, bladder, liver, and kidney cancers. The association of smoking with signature 5 mutations across these nine cancer types therefore includes some for which the risks conferred by smoking are modest and for which normal progenitor cells are not directly exposed to cigarette smoke (Table 1). Given the clocklike nature of signature 5 (17), its presence in the human germline (23), its ubiquity in cancer types unrelated to tobacco smoking (18), and its widespread occurrence in nonsmokers, it seems unlikely that signature 5 mutations associated with tobacco smoking are direct consequences of misreplication of DNA damaged by tobacco carcinogens. It is more plausible that smoking affects the machinery generating signature 5 mutations (24). Presumably as a consequence of the effects of smoking, signature 5 mutations correlated with age at the time of diagnosis in nonsmokers (P = 0.001) but not in smokers (P = 0.59).

Armitage Doll relates at most tangentially to what is being reported by these scientists.