WW II CR > less colon cancer

[Guest guest]

Hi All,

It seems there has been a study of World War II survivors who had reduced

calorie

intakes during the war have less colon cancer, as had previously been suggested

for

the Dutch famine during this war affecting breast cancer rates in later life.

The below is pdf-available.

Svensson E, Moller B, Tretli S, Barlow L, Engholm G, Pukkala E, Rahu M,

Tryggvadottir L.

Early life events and later risk of colorectal cancer: age-period-cohort

modelling

in the Nordic countries and Estonia.

Cancer Causes Control. 2005 Apr;16(3):215-23.

PMID: 15947873

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=pubmed & dopt=Abstra\

ct & list_uids=15947873 & query_hl=2

Introduction

There is evidence both from animal and epidemiological

studies that energy restriction during periods of growth

can lead to reduced risk of cancer [1–6].Natural ‘‘exper-

iments ’’, like World War II (WWII), when many coun-

tries suffered from limited food supply, provide valuable

possibilities to study the effect of energy restriction early

in life and later risk of disease.Wehave previously found a

decreased risk of colorectal cancer for the cohorts born in

Norway during or shortly after WWII (Figure 1) [7].A

study on the Dutch Hunger Winter 1944–1945 has also

shown a weak inverse relation between energy restriction

early in life and subsequent colon carcinoma [8].These

& #64257;ndings suggest that exogeneous factors, such as energy

restriction, acting very early in life may play a more

important role for colorectal cancer than hitherto recog-

nised.The protective effect of being born around WWII

has previously been shown for other cancer forms, such as

testicular cancer in Norway, Sweden, and Denmark [9,

10].Furthermore, the breast cancer risk was lower than

expected for women who experienced their puberty

during WWII in Norway [11], especially in non-food

producing (urban) areas [12].

During WWII, there were food rations in place in

Norway, with a reduction of up to 20% in energy intake

[13].The other Nordic countries experienced various

degrees of caloric restriction during WWII, ranging from

4% in Sweden to 17% in Finland [14].The energy

restriction in Estonia related to the war [15]is assumed to

be comparable to that in Norway.The energy restriction

during WWII was suf & #64257;cient to affect anthropometric

variables in the Nordic countries, and the magnitude of

the decrease in height and weight was associated with the

severity of the energy restriction prevailing in the respec-

tive country during the war [14].Accordingly, the purpose

of the present study was to investigate the effect of the

early life events later risk of colorectal cancer in the Nordic

countries and Estonia, focusing on the effect of WWII.

Results

There was a little change in colorectal cancer incidence

in Denmark, Sweden, and Iceland in the study period,

while there has been a large increase in incidence for

Estonia, Finland, and Norway during the past 40 years

(Figure 2) .Estonia had the highest average increase in

incidence of colorectal cancer with 23% and 16% per

& #64257;ve-year diagnostic period for males and females,

respectively.Both Norway and Finland had an increase

of around 10% , while the increase in Sweden, Denmark,

and Iceland was around 2–5% per & #64257;ve-year diagnostic

period.Most of the trends for colon and rectum

corresponded with each other, apart from some minor

exceptions.In both genders for Finland and in the

Estonian females, the increase in incidence over time for

rectal cancer was half of that of colon cancer.Denmark

had a slight negative downward trend for rectal cancer

for both genders.Despite these exceptions, it was

justifiable to combine the sub-site specific trends to

overall colorectal cancer trends.

Effects of age, period, and cohort

All countries showed a good & #64257;t to the full age-period-

cohort model (Table 1), with the exception of both

genders in Sweden and the Finnish females.They

showed over-dispersion in the full model, that is, there

were more variation than could be explained from pure

Poisson random variation.There were significant

effects of both diagnostic period and birth cohorts

for both genders in all countries (Table 2) .The

exceptions were non-significant cohort effect in Finnish

males, and non-significant cohort and period effects for

both genders in Iceland, possibly due to few numbers

of cases.

Effects of birth cohort

The main trend for Norway, Finland and Estonia, was a

steady increase in colorectal cancer risk with later year

of birth (Figure 3) .A drop in the estimated incidence

was observed for Norway and Estonia for the birth

cohorts born 1944–1948, followed by a steep increase

back to pre-war levels.The increasing trend in Finland

attenuated in the youngest cohorts.The incidence for

Denmark and Sweden was stable throughout the period,

however, with a decrease in risk from the cohort born in

1929–1933 onwards.The cohort effects for Iceland

varied from one cohort to the next.

The CE, with corresponding 95% con & #64257;dence inter-

val (95% CI), presented in Table 3, can be used to

provide a formal statistical assessment of the depar-

tures from linear trends observed in Figure 3.CEs

with corresponding 95% CIs not encompassing 1.0,

were regarded as significant deviations from the

observed linearity.Due to the problems pertaining

to multiple-significance testing, only point estimates

being significant for both genders, or significant in

one gender and a point estimate in the same direction

for the other gender, were considered significant.

Accordingly, based on Table 3, the following birth

cohorts were considered significant:1939–1943, a

downward trend for both genders in Norway;1944–

1948, upward curvature for both genders in Norway

and Estonian females, together with a non-significant

upward point estimate in the Estonian males.The

latter & #64257;nding indicates that there has been a drop in

risk from 1939–1943 to 1944–1948 and again increas-

ing to 1949–1953.

Table 3 . Curvature effects ( CE), and 95% con & #64257;dence intervals ( 95%

CI)

of cohort estimates in the Nordic countries and Estonia 1958–1997 ( bold

indicates

significance at p < 0.05)

----------------------------------------------------------

Variable----Norway CE Sweden CE Denmark CE Finland CE Iceland CE Estonia CE

--------M F M F M F M F M F M F

Cohort

1879–1883 1.23 1.00 0.98 1.01 1.00 1.03 0.82 0.74

( 0.9–1. 6) ( 0.8–1. 3) ( 0.8–1. 2) ( 0.8–1. 2) ( 0. 8–1.2) ( 0.9–1. 2) (

0.5–1. 3) ( 0.5–1. 2)

1884–1888 0.92 1.00 0.87 0.80 0.99 0.98 1.14 0.96

( 0.8–1. 1) ( 0.8–1. 2) ( 0.8–1. 0) ( 0.7–0. 9) ( 0. 9–1.1) ( 0.9–1. 1) (

0.9–1. 5) ( 0.8–1. 2)

1889–1893 0.99 0.99 1.03 1.04 0.94 0.97 0.98 1.02 1.10 1.56 1.31 0.16

( 0.9–1. 1) ( 0.9–1. 1) ( 1.0–1. 1) ( 1.0–1. 1) ( 0. 9–1.0) ( 0.9–1. 1) (

0.8–1. 2) ( 0.9–1. 2) ( 0.4–3. 0) ( 0.6–4. 3) ( 0.6–2. 8) ( 0. 7–1.8)

1894–1898 0.98 0.92 0.98 0.97 0.98 1.01 1.01 0.79 1.26 0.62 0.59 1.04

( 0.9–1. 1) ( 0.8–1. 0) ( 0.9–1. 1) ( 0.9–1. 0) ( 0. 9–1.1) ( 0.9–1. 1) (

0.9–1. 2) ( 0.7–0. 9) ( 0.6–2. 6) ( 0.3–1. 2) ( 0.4–0. 9) ( 0. 8–1.4)

1899–1903 1.01 1.07 1.03 1.00 1.08 1.01 1.05 1.18 0.83 1.18 1.33 1.05

( 0.9–1. 1) ( 1.0–1. 2) ( 1.0–1. 1) ( 0.9–1. 1) ( 1. 0–1.2) ( 0.9–1. 1) (

0.9–1. 2) ( 1.1–1. 3) ( 0.5–1. 4) ( 0.7–2. 0) ( 1.0–1. 8) ( 0. 8–1.3)

1904–1908 1.00 1.02 1.00 1.01 0.93 1.01 1.02 0.93 1.01 1.06 1.02 1.07

( 0.9–1. 1) ( 1.0–1. 1) ( 0.9–1. 0) ( 1.0–1. 1) ( 0. 9–1.0) ( 1.0–1. 1) (

0.9–1. 1) ( 0.8–1. 0) ( 0.6–1. 6) ( 0.7–1. 7) ( 0.8–1. 3) ( 0. 9–1.3)

1909–1913 1.02 1.01 0.96 0.99 1.09 1.01 0.95 0.95 0.99 0.88 0.83 0.74

( 0.9–1. 1) ( 0.9–1. 1) ( 0.9–1. 0) ( 0.9–1. 0) ( 1. 0–1.2) ( 1.0–1. 1) (

0.9–1. 1) ( 0.9–1. 0) ( 0.6–1. 5) ( 0.6–1. 4) ( 0.7–1. 0) ( 0. 6–0.9)

1914–1918 1.04 0.99 1.11 1.10 0.96 0.96 0.99 1.12 1.22 1.09 1.26 1.59

( 1.0–1. 1) ( 0.9–1. 1) ( 1.1–1. 2) ( 1.0–1. 2) ( 0. 9–1.0) ( 0.9–1. 0) (

0.9–1. 1) ( 1.0–1. 2) ( 0.8–1. 9) ( 0.7–1. 7) ( 1.0–1. 6) ( 1. 3–1.9)

1919–1923 0.96 1.01 0.90 0.89 1.03 1.03 1.04 0.92 0.82 0.97 0.93 0.72

( 0.9–1. 0) ( 0.9–1. 1) ( 0.9–1. 0) ( 0.8–1. 0) ( 1. 0–1.1) ( 1.0–1. 1) (

0.9–1. 2) ( 0.8–1. 0) ( 0.5–1. 3) ( 0.6–1. 6) ( 0.8–1. 2) ( 0. 6–0.9)

1924–1928 0.93 0.97 1.06 1.04 1.04 1.03 1.05 1.05 1.14 1.02 0.89 1.06

( 0.9–1. 0) ( 0.9–1. 1) ( 1.0–1. 1) ( 1.0–1. 1) ( 1. 0–1.1) ( 0.9–1. 1) (

0.9–1. 2) ( 0.9–1. 2) ( 0.7–1. 9) ( 0.6–1. 9) ( 0.7–1. 1) ( 0. 9–1.3)

1929–1933 1.14 1.02 0.93 0.99 0.87 0.99 0.89 1.06 0.59 0.92 0.94 0.90

( 1.0–1. 3) ( 0.9–1. 2) ( 0.8–1. 0) ( 0.9–1. 1) ( 0. 8–1.0) ( 0.9–1. 1) (

0.8–1. 0) ( 0.9–1. 3) ( 0.3–1. 2) ( 0.5–1. 9) ( 0.8–1. 2) ( 0. 7–1.1)

1934–1938 0.92 1.00 0.98 0.85 1.02 0.89 0.99 0.98 1.70 0.97 0.84 1.04

( 0.8–1. 1) ( 0.8–1. 2) ( 0.9–1. 1) ( 0.7–1. 0) ( 0. 8–1.2) ( 0.8–1. 0) (

0.8–1. 2) ( 0.8–1. 2) ( 0.6–4. 8) ( 0.4–2. 6) ( 0.6–1. 2) ( 0. 8–1.4)

1939–1943 0.74 0.73 1.06 1.14 0.94 0.91 1.10 0.90 1.59 1.18 1.31 0.69

( 0.6–0. 9) ( 0.6–0. 9) ( 0.9–1. 3) ( 0.9–1. 4) ( 0. 8–1.2) ( 0.8–1. 1) (

0.9–1. 4) ( 0.7–1. 2) ( 0.5–5. 6) ( 0.3–4. 3) ( 0.8–2. 0) ( 0. 5–1.1)

1944–1948 1.66 1.42 0.90 0.95 1.27 0.97 0.82 0.89 0.25 1.13 1.34 2.16

( 1.2–2. 3) ( 1.0–2. 0) ( 0.7–1. 2) ( 0.7–1. 2) ( 0. 9–1.7) ( 0.9–1. 0) (

0.6–1. 2) ( 0.6–1. 3) ( 0.1–1. 3) ( 0.2–7. 6) ( 0.7–2. 6) ( 1. 1–4.3)

Discussion

The present study, demonstrates that the previously

observed lower risk for those being born during WWII

on later colorectal cancer risk in Norway [7]also

prevails in Estonia.Energy restriction is a possible

explanation for these & #64257;ndings, since both countries

suffered from poor nutritional conditions during the war

[13, 15], and because experimental and epidemiological

data support a connection between energy restriction in

early life and reduced cancer risk [1–6].Further,

previous Norwegian data showing that the height and

weight of school children were transiently reduced

during WWII, lend support to the notion that the poor

nutritional conditions during the war had biological

implications in this population [21].Comparable

anthropometric data from Estonia are not available,

but there are some indications of a catch-up growth in

children and adolescents after WWII [15], suggestive of

some caloric restriction during the war.

A significant cohort effect of WWII on colorectal

cancer risk was observed only in Norway and Estonia,

the two countries with the largest energy restriction.

Although less consistent than in Norway and Estonia, a

birth cohort effect of WWII on colorectal cancer risk

may be implicated also in Sweden and Denmark, an

observation also apparent in other publications [22, 23].

On the other hand, it is also conceivable that the energy

restriction of 4% –7% in these two countries was too

small;in line with animal studies showing that a

restriction of more than 10% is necessary to inhibit

carcinogenesis [24, 25].Iceland had too few colorectal

cancer cases to provide an easily interpretable pattern.

The secular trend of this country was slightly upwards,

which also & #64257;ts with Iceland being poor before WWII,

then having a boost in the economy during and after the

war.

An unexpected & #64257;nding was the lack of birth cohort

effect on colorectal cancer risk in Finland, given its

estimated 17% decrease in energy intake during WWII

[14].The Finnish people have a different genetic

background than the other Nordic countries, but share

common ancestors with the Baltic states [26].Since a

war-related birth cohort effect was found in Estonia, a

genetic difference is not likely to explain the lack of

observed risk reduction in Finland.Other factors related

to the nutritional status in Finland may explain why this

country came out differently.Firstly, before WWII, the

height of Finnish children aged 7–13 was around two to

& #64257;ve cm lower compared to those of the other Nordic

countries [14].According to dietary surveys and calcu-

lations performed in Finland in the 1930s by the

National Nutrition Committee, about one third of the

school children had an inadequate diet caused by

& #64257;nancial deprivation [27].It is thus conceivable that

the Finnish children were less affected by the energy

restriction during WWII due to a lower baseline

nutritional status compared to their Nordic counter-

parts.Secondly, 70,000–80,000 Finnish children were

sent to Sweden during WWII [28], which may have

counteracted the effect of the caloric restriction among

these cohorts.

One shortcoming of the present study is that no

individual data on exposure were available on the

colorectal cancer cases.Our interpretation of the current

& #64257;ndings rests on the assumption that the energy restric-

tion imposed on the respective populations in general

affected young ones to the same degree as adults.We

believe that the observed reduction in anthropometric

variables during WWII in the Nordic school children

roughly comparable to the prevailing nutritional condi-

tion in the respective country [14], makes it likely that

the children suffered from the same energy restriction as

the population as a whole.

Our interpretation of an association between early life

conditions and colorectal cancer risk could have been

& #64258;awed if the WWII birth cohorts were living less cancer

prone throughout life than the pre-and post-war

cohorts.If that were the case, our colorectal cancer

protection attributed to conditions during WWII was

rather a result of events later in life.There is, however, no

reason to believe that the WWII birth cohorts have been

living differently from the remaining population in the

respective country with respect to the established risk

factors for colorectal cancer such as nutritional condi-

tions, smoking habits, physical activity, use of hormone

replacement therapy, or non-steroidal anti-in & #64258;ammatory

drugs.It is thus dif & #64257;cult to explain how the observed

cohort specific risk pattern could have arisen by expo-

sures other than those pertaining to WWII.

The & #64257;nding of this study strengthens the hypothesis

that colorectal cancer may be affected by energy

restriction early in life, but the biological mechanisms

being involved remain elusive.The energy restriction

during WWII clearly involved a decreased glycemic

load, as evidenced by a substantial reduction in the

incidence of type 2 diabetes in Oslo in this period [29],

and there are thus reasons to believe that the circulat-

ing levels of insulin and insulin-like growth factors

[iGFs]were also reduced.The role of insulin and the

IGF-axis as risk factor for colorectal cancer on a short

term basis is well established [30–32], but could also be

a plausible mechanism underlying the long-term cancer

protective effect of caloric restriction.Gunnell and

colleagues [33]have postulated that IGF-I levels in

adulthood are programmed by nutrition in early life,

recently supported in an animal study, but only for

males [34].A study in humans, however, demonstrated

that exposure to severe short-term restriction during

the Dutch hunger winter during childhood, increased

rather than reduced plasma levels of IGF-I on a

permanent basis [35].This was a rather small study,

but similar overshoot effects have also been observed

in mice subjected to refeeding subsequent to caloric

restriction [36].The nature of the association between

early life nutrition and IGF-I levels later in life is thus

still unclear.

A long-term effect of IGF-I could, however, be

mediated indirectly.Energy restriction or low IGF-I

concentration in infancy lead to stunted growth and a

reduction in the number of cells, including a lower

number of stem cells [37].Albanes and Winick have

earlier related the incidence of colon cancer to the

number of colonic mucosal cells undergoing mitosis [38].

Thus, the protective mechanism of energy restriction

early in life may be as a result of fewer stem cells,

following the hypothesis of fewer cells, fewer potentials

for malignancy [38].

Another possible mechanism linking diet in childhood

to colorectal cancer risk in adulthood involves the

adipokine leptin, a hormone produced by adipocytes.

Apart from regulating energy balance and fertility,

leptin has been shown to stimulate growth of cancer

cells from colon as well as other organs [39–41].There is

also epidemiological evidence that leptin is a risk marker

for colorectal cancer [42].Studies both in animals and

humans have shown that food deprivation in critical

time periods early in life leads to lower circulating levels

of leptin both on a short-and long-term [43, 44].Leptin

may thus be one factor linking early nutrition to later

colorectal cancer risk.

A sporadic case of colorectal cancer is generally

regarded as the result of long-term exposure to risk

factors acting over several decades [45].However, our

& #64257;ndings suggest that a perturbation such as a caloric

restriction early in life, or possibly the removal of an

early carcinogenic factor, may have a bene & #64257;cial impact

on the colorectum that prevails into adulthood.It

further suggests that some kind of programming is

taking place during early life, which sets the stage for the

susceptibility of the colorectal stem cells to undergo

malignant transformation later in life.As such, our

& #64257;ndings clearly warrant epidemiological studies in other

populations as well as in vitro experiments to elucidate

their biological basis, as well as timing, together with

continual observation of these Nordic cohorts as they

grow older.

Al Pater, PhD; email: old542000@...

__________________________________

Discover

Stay in touch with email, IM, photo sharing and more. Check it out!

http://discover./stayintouch.html