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Z Gastroenterol 2015; 53(08): 782-788
DOI: 10.1055/s-0035-1553476
Übersicht
© Georg Thieme Verlag KG Stuttgart · New York

Klinisch relevante, geschlechtsspezifische Unterschiede beim kolorektalen Karzinom (KRK)

Clinically relevant, gender-specific differences in colorectal carcinoma (CRC)
N. Höffken
,
J. Leichsenring
,
A. Reinacher-Schick
Further Information

Publication History

05 April 2015

06 July 2015

Publication Date:
18 August 2015 (online)

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Zusammenfassung

Weltweit treten kolorektale Karzinome bei Männern aller Altersgruppen häufiger auf als bei Frauen. Die typischen Risikofaktoren wie Rauchen, Übergewicht, ballaststoffarme Kost und fleischreiche Ernährung können den geschlechtsspezifischen Unterschied nicht allein erklären. Eine wichtige Rolle in der Pathogenese der Erkrankung scheinen die Östrogene zu spielen. Dies erklärt, warum prämenopausale Frauen ein niedriges Risiko haben zu erkranken. Im gesunden Kolon werden Östrogenrezeptoren ERß exprimiert. Bei der Entwicklung eines Kolonkarzinoms nehmen diese signifikant ab. Den Östrogenen wird ein protektiver Effekt zugeschrieben. Möglicherweise fungieren sie als Tumorsuppressor oder über einen Einfluss auf die Signalwege der Karzinogenese. Die genaue Rolle der Östrogene bei der Karzinogenese des Kolonkarzinoms ist jedoch weiterhin unklar.

Auch die Lokalisation der Kolonkarzinome ist in Abhängigkeit vom Geschlecht und Alter unterschiedlich. Frauen nach der Menopause weisen einen Shift der Tumorlokalisation in das rechte Kolon auf. Hier wird ein Zusammenhang mit einem erhöhten MSI-H-Status vermutet.

Zu den geschlechtsspezifischen Unterschieden der adjuvanten und palliativen Therapie des kolorektalen Karzinoms gibt es praktisch keine prospektiv randomisierten Studien. Ältere Registerarbeiten weisen darauf hin, dass Frauen postoperativ eine bessere Prognose aufweisen, Männer jedoch von einer adjuvanten Therapie mehr profitieren. Möglicherweise spielt hier eine gesteigerte 5-FU-Toxizität bei Frauen eine Rolle. In der palliativen Therapie gibt es nur wenige geschlechtsspezifische Analysen. Vor allem Frauen mit rechtsseitigen Kolonkarzinomen scheinen unter einer Anti-EGFR-Therapie ein deutlich schlechteres Ansprechen aufzuweisen als Männer mit linksseitigen Karzinomen. Geschlechtsspezifische Unterschiede sollten zukünftig häufiger in randomisierte Studien mit einbezogen werden.

Abstract

The incidence of colorectal cancer worldwide is higher in men. Risk factors like smoking, overweight, or dietary exposures cannot explain this gender difference. In the pathogenesis of colorectal carcinoma, estrogen seems to play an important protective role. Estrogen may reduce the risk of developing colon cancer in premenopausal women.

The expression of estrogen receptor ß in healthy colon is significantly decreased in the development of colon cancer. The role of estrogen in pathogenic pathways is most likely protective or might serve as a tumor suppressor. However, the exact role of estrogen in the carcinogenesis of colorectal cancer still remains unclear.

Furthermore, tumor localization depends on age and gender. Therefore, in postmenopausal women there is a shift to predominantly right-sided cancers. Here, a link between tumor localization and MSI-H (microsatellite-high) status can be assumed.

There are virtually no prospective randomised trials in adjuvant or palliative therapy of patients with colorectal cancer. Earlier data from registries point to a better post-operative survival of women, while men seem to benefit more from adjuvant therapy. Potentially, there may be a role of an increased toxicity to 5-FU in women. In the palliative setting, there are also only few gender-specific analyses. Women with right-sided colon cancers show a significant worse response and survival under an anti-EGFR antibody treatment compared with men and left-sided cancers. A focus on gender-specific differences should be incorporated more often in future randomised trials.

Schlüsselwörter

Geschlecht - Kolonkarzinom - MSI - Östrogen - Therapie

Key words

gender - colon carcinoma - MSI - estrogen - therapy
 

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