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Doktorsavhandling vid Karolinska Institutet
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Friberg, Emilie
Diet and Endometrial Cancer : Insulin related factors
Fredagen den 29 maj 2009, kl. 13.00.
Samuelssonsalen, Tomtebodavägen 6.
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ISBN: 978-91-7409-422-0
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Diss: 09:158
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Abstract:
There is accumulating evidence that insulin resistance and hyperinsulinemia are involved in
the etiology of endometrial cancer. Dietary intake can influence insulin levels especially
among individuals who are already insulin resistant.
Coffee drinking has been reported to have beneficial effects on insulin sensitivity.
Glycemic index and load are concepts developed to quantify the glycemic response and
insulin demand to carbohydrates in different foods. A moderate alcohol intake has been
shown to improve insulin sensitivity whereas a higher intake has been shown to increase
estrogen levels which unbalanced by progesterone may increase the risk of endometrial
cancer. In the analyses we used data from the Swedish Mammography Cohort, a populationbased
prospective cohort study including over 60 000 women, born 1914-48, among whom
689 endometrioid adenocarcinoma cases were diagnosed through 2007 (17.6 years of followup).
We examined the association between coffee consumption, carbohydrate intake,
glycemic index, glycemic load and alcohol consumption at baseline 1987-90 and in 1997 and
endometrial cancer risk using Cox proportional hazards models.
To quantitatively summarize the association between alcohol, diabetes and the risk of
endometrial cancer, we conducted meta-analyses of published studies. In the meta-analyses
we identified studies by literature searches of the databases PubMed and Embase and by
searching the reference lists of relevant articles. We summarized the relative risks (RRs) with
95% confidence intervals (CIs) using random-effects models and in the meta-analysis of
alcohol also with a dose-response random-effect meta-regression model.
Drinking four cups or more of coffee per day was overall associated with a 25% decreased
risk of endometrial cancer as compared to one cup of coffee or less per day. The association
seemed to be largely confined to overweight and obese women.
We observed no overall association between carbohydrate intake, glycemic index, or
glycemic load and the incidence of endometrial cancer. Among overweight and obese
women with low physical activity, who completed the questionnaire in 1997, carbohydrate
intake and glycemic load were positively related to endometrial cancer risk. In this subgroup,
the RRs comparing extreme quartiles were 1.90 (95% CI 0.84-4.31) for carbohydrate intake
and 2.99 (95% CI 1.17-7.67) for glycemic load.
We observed no association between alcohol and endometrial cancer risk in the Swedish
elderly study population with a generally low consumption. However, in the meta-analysis of
alcohol and endometrial cancer incidence based on 7 cohort studies, we observed a
statistically significant inverse association with low consumption as compared to nondrinkers
and a higher risk associated with 2 drinks or more per day.
In the meta-analysis of diabetes and endometrial cancer, based on 16 studies, we found
that diabetes was significantly associated with an increased risk of endometrial cancer
(summary RR 2.10 95% CI 1.75-2.53). The meta-analysis of type 1 diabetes and endometrial
cancer was based on three studies and also found a significant positive association.
In conclusion, our results indicate that dietary factors related to insulin resistance and
hyperinsulinemia as well as diabetes may play an important role in the development of
endometrial cancer. Hyperinsulinemia may stimulate proliferation of endometrial cells both
through insulin-like growth factors and by increased levels of unbound estrogens.
List of papers
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Coffee drinking and risk of endometrial cancer: A population-based prospective cohort study.
Emilie Friberg, Nicola Orsini, Christos S. Mantzoros and Alicja Wolk.
International Journal of Cancer,
1970
In Print
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Carbohydrate intake, glycemic index, and glycemic load in relation to risk of endometrial cancer: A prospective study of Swedish women.
Susanna C. Larsson, Emilie Friberg and Alicja Wolk.
International Journal of Cancer,
2007;
120(5):
1103-7
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Long-term Alcohol Consumption and Risk of Endometrial Cancer Incidence: A Prospective Cohort Study.
Emilie Friberg and Alicja Wolk.
Cancer Epidemiol Biomarkers Prev.,
2009;
18(1):
355-8
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Alcohol consumption and risk of endometrial cancer: A Meta-Analysis of prospective studies.
Emilie Friberg, Nicola Orsini, Christos S. Mantzoros and Alicja Wolk.
Submitted
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Diabetes mellitus and risk of endometrial cancer: A Meta-Analysis.
Emilie Friberg, Nicola Orsini, Christos S. Mantzoros, and Alicja Wolk.
Diabetologia,
2007;
50(7):
1365-74
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