a. Yes: Tomasetti and Vogelstein (2015)11

Abstract. “Some tissue types give rise to human cancers millions of times more often than other tissue types. Although this has been recognized for more than a century, it has never been explained. Here, we show that the lifetime risk of cancers of many different types is strongly correlated (0.81) with the total number of divisions of the normal self-renewing cells maintaining that tissue’s homeostasis. These results suggest that only a third of the variation in cancer risk among tissues is attributable to environmental factors or inherited predispositions. The majority is due to ‘bad luck,’ that is, random mutations arising during DNA replication in normal, noncancerous stem cells. This is important not only for understanding the disease but also for designing strategies to limit the mortality it causes.”(p78)

b. No: Rose (1985)22

“If everyone smoked 20 cigarettes a day, then clinical, case–control and cohort studies alike would lead us to conclude that lung cancer was a genetic disease; and in one sense that would be true, since if everyone is exposed to the necessary agent, then the distribution of cases is wholly determined by individual susceptibility.”(p32)

“Within Scotland and other mountainous parts of Britain there is no discernible relation between local cardiovascular death rates and the softness of the public water supply. The reason is apparent if one extends the enquiry to the whole of the UK. In Scotland, everyone's water is soft. . . . Everyone is exposed, and other factors operate to determine the varying risk.

Epidemiology is often defined in terms of study of the determinants of the distribution of the disease; but we should not forget that the more widespread is a particular cause, the less it explains the distribution of cases. The hardest cause to identify is the one that is universally present, for then it has no influence on the distribution of disease.”(p32–33)

c. No: Weinberg and Zakin (2015)8

“R2 does not explain much. . . . Consider the following hypothetical thought experiment. Suppose an evil agent exposes the entire US population to a powerful new carcinogen that doubles the incidence of all 31 cancers. One might conclude that the fraction explained by this exposure must be one-half, because half the cases would not have occurred had they not been exposed; one might then reason that the fraction explained by stochastic errors in stem cell division would now be correspondingly smaller. But even with the new two-fold higher incidence numbers, the correlation would not change at all, because the points (all being on a log scale) would rigidly shift upward, each by log (2). The fraction of the variability in log incidence that is ‘explained’ (in the statistical sense) by the number of stem cell divisions would remain at 2-thirds. Similarly, if the population were administered an anticancer vaccine that could prevent the occurrence of half of cancers, regardless of type, the correlation would still be 2-thirds. Clearly one cannot infer from the Tomasetti and Vogelstein data that 2-thirds of cancer is unpreventably due to bad luck.”

“One cannot partition causes into fractions that add up to 1. . . . environmental exposures, germ-line genetic variants and random events like replicative errors typically act in concert; the effects cannot be treated as separable. It is a mistake to assume that one can partition etiologic factors into contributions that sum to 1.0, as in the notion that two-thirds of cancers are due to bad luck and therefore at most one-third could be due to environmental and inherited genetic factors.”

“Because of joint effects, contributing causes often have attributable fractions that add to more than 1.0. The intellectual disability syndrome secondary to phenylketonuria is a well known example where the fraction attributable to genetics is 1.0, while the fraction attributable to environment is also 1.0, because the outcome requires both a dysfunctional metabolic gene and an environmental exposure (dietary phenylalanine). As another example, the fact that 100% of prostate cancer is due to a stochastic event (the random inheritance of a Y chromosome) does not relieve us of the need to search out other causes, some of which may be preventable.”