Page 84 - 20dynamics of cancer

HISTORY OF THEORIES 69

200
180
160
Citations per year 120
140

100
80
60
40

20
0
1971 1974 1977 1980 1983 1986 1989 1992 1995 1998 2001 2004

Year

Figure 4.1 Citations per year for Knudson (1971) as of August, 2005.

4.3 Cancer Is a Genetic Disease

The role of somatic mutations in cancer was debated for many years.
Witkowski (1990) puts that historical debate in context with a compre-
hensive time line of developments in cancer research interleaved with
developments in basic genetics and molecular biology (see also Knudson
2001). Here, I mention a few of the highlights that provide background
for evaluating theories of progression and incidence.
Boveri (1914, 1929) often gets credit for the first comprehensive the-
ory of somatic genetic changes in cancer progression (Wunderlich 2002).
Tyzzer (1916) used the term “somatic mutation” to describe events in
cancer progression. In the 1950s, Armitage and Doll (1954, 1957) cau-
tiously described the stages of multistage progression as possibly re-
sulting from somatic mutations but perhaps arising from other causes.
Burdette (1955), in a comprehensive review of the role of genetic muta-
tions in carcinogenesis, tended to oppose the central role of mutations
in progression. In (1969), Fould’s extensive summary of cancer progres-
sion also downplayed the role of mutation.