Biomedical Engineering Reference
In-Depth Information
3.2. The Mixed Models of Carcinogenesis
In the population, for the same type of cancer, dierent individual may
involve dierent pathways or dierent number of stages (see [41, 54, 55, 56,
57, 59, 60, 61, 62]). These models have been referred by Tan
54;55
and Tan
and Singh
62
as mixed models of carcinogenesis. These models are basic
consequences of the observations: (1) Dierent individuals are subject to
dierent environmental conditions, (2) the mutation of critical cancer genes
can occur in either germline cells or in somatic cells, and (3) As shown in
the previous section, the same cancer can be derived by several dierent
pathways, referred to as multiple pathways.
To serve as an example, consider again the human colon cancer. The
multiple pathways for human colon cancer as described in the previous sec-
tion then leads to the following 5 dierent pathways: The sporadic LOH
(about 70%, see Figure 1), the familial LOH (FLOH, about 10-15%), the
FAP (Familial Adenomatous Polys, about 1%), the sporadic MSI (about
10-15%, see Figure 2) and the HNPCC (Hereditary Non-Polyposis Colon
Cancer, about 4-5%). For sporadic pathways, the individuals at birth are
normal individuals and do not carry any mutated or inactivated suppres-
sor genes. For FAP, the individual has inherited a mutated APC gene
in chromosome 5 at birth. For HNPCC, the individuals has inherited a
mutated mis-match gene hMLH1 or hMSH2. For the familial colon can-
cer, the individuals have inherited a low penetrance mutated gene such as
APCI1307K at birth. Hence, FAP and FLOH are special cases of the APC-
cateninT cfmyc pathway and HNPCC a special case of the MSI
pathway.
The above indicates that from the population perspective, the human
colon cancer can best be described by a mixture of ve pathways. Let Y
j
be
the number of people who develop colon cancer during the jth age group
[t
j1
; t
j
). The above then indicates that the probability density of Y
j
is:
X
5
P (Y
j
) =
!
i
(j)f
i
(Y
j
;
i
);
i=1
where f
i
(Y
j
;
i
) is the probability that the individual develops colon cancer
during the jth age group [t
j1
; t
j
) by the ith pathway and where !
i
(j)
is the proportion for the ith pathway during the jth age group; see
Remark 4
Remark 4: Notice that !
i
(j) is a function of j (the age group). For the
earlier age group, one may expect that most of the colon cancer cases are
Search WWH ::
Custom Search