Insulin resistance and cancer: Epidemiological
Shoichiro Tsugane1and Manami Inoue
Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan
(Received November 24, 2009 ⁄Revised January 8, 2010 ⁄ Accepted January 28, 2010)
Over the last 60 years, Japanese people have experienced a rapid
and drastic change in lifestyle, including diet. Suspicions have
been raised that so-called ‘Westernization’, characterized by a
high-calorie diet and physical inactivity, is associated with increas-
ing trends in the incidence of cancer of the colon, liver, pancreas,
prostate, and breast, as well as type 2 diabetes. Epidemiological
evidence from our prospective study, the Japan Public Health Cen-
ter-based Prospective (JPHC) study, and systematic literature
reviews generally support the idea that factors related to diabetes
or insulin resistance are associated with an increased risk of colon
(mostly in men), liver, and pancreatic cancers. These cancers are
inversely associated with physical activity and coffee consump-
tion, which are known to decrease the risk of type 2 diabetes. The
suggested mechanism of these effects is that insulin resistance
and the resulting chronic hyperinsulinemia and increase in bio-
available insulin-like growth factor 1 (IGF1) stimulate tumor
growth. In contrast, associations with diabetes are less clear for
cancer of the colon in women, and breast and prostate, which are
known to be related to sex hormones. The effect of insulin resis-
tance or body fat on sex-hormone production and bioavailability
may modify their carcinogenic effect differently from cancers of
the colon in men, and liver and pancreas. In conclusion, there is
substantial evidence to show that cancers of the colon, liver, and
pancreas are associated with insulin resistance, and that these can-
cers can be prevented by increasing physical activity, and possibly
coffee consumption. (Cancer Sci 2010)
nomic growth occurring following World War II has been
accompanied by the so-called ‘Westernization’ of lifestyle, char-
acterized by a high-calorie diet and physical inactivity. Parallel-
ing this change, the mortality of infectious diseases has
decreased while that of lifestyle-related diseases such as cancer
and heart disease has increased. Cancer has been the leading
cause of death since 1981, and now accounts for 30% of all
deaths. Among various cancer sites, cancers of the colon, pan-
creas, breast, and prostate, which are known to be more common
in Western countries, have increased in Japan. Most but not all
of these cancers have been shown to be associated with greater
body (or abdominal) fatness and physical inactivity.
Here, we review the associations observed in our prospective
study, the Japan Public Health Center-based Prospective (JPHC)
study, between body fatness, diabetes, physical activity, coffee
consumption (which may affect diabetes), and the risk of cancer,
as well as the epidemiological literature on this topic. Evidence
is discussed with a special focus on the role of insulin resistance.
In brief, the JPHC study conducted a baseline survey of regis-
tered residents aged 40–69 years in 11 public health center areas
nationwide in 1990–1994. Approximately 110 000 subjects
apanese people have experienced a rapid and drastic change
in lifestyle, including diet. The industrialization and eco-
returned the questionnaire, giving a response rate of 81.0%, and
50 000 provided blood and health check-up data.(1)The subjects
have been followed for vital status and the occurrence of cancer
and other diseases, and 5- and 10-year follow-up surveys have
been conducted to update information on lifestyle and health
Time trend analysis
According to the annual National Nutrition Survey by the Minis-
try of Health, Labour and Welfare (MHLW) (Fig. 1), and allow-
ing for the lack of age-adjustment, total energy intake (per
capita per day) increased from 1903 kcal in 1946 to peak at
2287 kcal in 1971. It then followed a downward trend, decreas-
ing to 1891 kcal in 2006. The rapid increase in fat intake
(14.7 g in 1946 to 48.7 g in 1971) owed mainly to the increase
in total energy during the period of post-war reconstruction and
high economic growth. The constant decrease in carbohydrate
intake and leveling off of fat intake resulted in a decreasing
trend in total energy intake after the mid-1970s, probably when
physical activity decreased (due to the spread of electrification
and automobile use in daily life and at the workplace) and the
westernization of Japanese dietary habits plateaued.
In Japan, age-adjusted mortality rates of colon, liver, and pan-
creatic cancers steadily increased up to the mid-1990s, and then
flattened out or decreased. The exception to this trend was liver
cancer, which switched from a decrease to an increase around
the 1970s, probably due to endemic hepatitis virus infection
(Fig. 2). Cancer incidence rates for Japanese people are only
available for the years after 1975 and the quality of incidence
data is not considered high enough to allow comparison of long-
term trends.(2)However, allowing for this insufficient quality,
incidence rates of these cancers have fluctuated in parallel with
mortality rates. For cancer of the liver and pancreas in particu-
lar, mortality rate can be deemed as a substitute for incidence
rate due to their poor prognoses.
These trends in dietary and cancer mortality pattern appear to
be parallel with a lag time of approximately 20 years. Cancers
of the colon, liver, and pancreas might therefore be associated
with energy imbalance, with incubation periods of 20 years.
Cancers of the breast and prostate have shown different trends,
however, increasing even after the mid-1990s. The etiology of
these cancers may differ somewhat from those of the colon,
liver, and pancreas.
This parallel trend in suspected energy imbalance and cancers
of the colon, liver, and pancreas may indirectly support a
close link with insulin resistance, as characterized by energy
1To whom correspondence should be addressed. E-mail: firstname.lastname@example.org
ª ª 2010 Japanese Cancer Association
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Tsugane and InoueCancer Sci |
ª ª 2010 Japanese Cancer Association