Page 313 - 20dynamics of cancer

298 CHAPTER 14

(a) colon
70
60
50
40 X
X X X
30 X X X X
Average methylation 10 X (b) endometrium X
20
X
X
X
0
70
≥ 3
obese children
60
+
50
−
+ − − +
40 − +
30
20
10
0
0 20 40 60 80
Age

Figure 14.5 DNA methylation measures mitotic age. (a) Methylation increases
steadily in the colon with chronological age, reflecting the continual mitosis
in this tissue throughout life. (b) In the endometrium, methylation increases
steadily with age during menstrual cycling and then plateaus after menopause.
Obese women (filled symbols) have higher estrogen levels and greater endome-
trial turnover than non-obese women (open symbols). Obese women also have
greater methylation than non-obese women, supporting the idea that methy-
lation measures number of mitoses: 7 of 8 obese samples fall above the line,
whereas 11 of 17 non-obese women fall below the line. Women with fewer than
three children (stars) have more menstrual cycles and endometrial renewal than
women with three or more children (circles). Women with few children have
greater methylation: 11 of 14 women with less than three children fall above
the line, whereas 9 of 11 women with more than three children fall below the
line. Redrawn from Shibata and Tavare (2006), based on original studies in
Yatabe et al. (2001) and Kim et al. (2005).

Various lines of evidence show that the frequency of methylation at
certain genomic sites increases with the number of mitoses (Shibata and