(Apr 2012) Commentary: Link between endometriosis and ovarian-cancer subtypes : The Lancet Oncology

Link between endometriosis and ovarian-cancer subtypes : The Lancet Oncology

"Previous large epidemiological studies have attempted to identify benign gynaecological disorders that predispose to the development of epithelial ovarian cancer. The only disorder that has been repeatedly1—4 (although not universally5) associated with this cancer is endometriosis. Results of some of these studies have suggested a specific link with endometrioid and clear-cell ovarian cancers, but until now none had the power to allow definitive subgroup analysis based on a contemporary definition of histological subtype.

 

In a study reported in the Lancet Oncology, Celeste Leigh Pearce and colleagues6 assessed self-reported endometriosis data from 13 pooled case—control studies in the Ovarian Cancer Association Consortium (OCAC). They confirm that a history of endometriosis is significantly associated with an increased risk of clear-cell (odds ratio 3·05, 95% CI 2·43—3·84) and endometrioid (2·04, CI 1·67—2·48) ovarian cancers, and for the first time show an association with low-grade serous ovarian cancer (2·11, 1·39—3·20). No association was noted between endometriosis and high-grade serous, mucinous, serous borderline, or mucinous borderline ovarian cancers.

 

With more than 23 000 participants (7911 with a diagnosis of ovarian cancer), the main strengths of this study are its statistical power and its robust methods. Incidences of reported endometriosis differ substantially between the pooled studies. Although clinicopathological and genetic differences between the populations could reasonably be expected, importantly there was no significant heterogeneity of the association with histological subtype in the different studies.

The main truly novel finding is an association between a history of endometriosis and low-grade serous ovarian cancer. Perhaps surprisingly, serous borderline tumours (from which invasive low-grade serous ovarian cancers are believed to arise7) are not also associated with a history of endometriosis. Pearce and colleagues showed the crude odds ratio of serous borderline tumours was 1·31 (95% CI 1·05—1·63), but this was corrected to 1·20 (0·95—1·52) by stratification for age and ethnic origin, and by adjustment for oral contraceptive use. Perhaps, even in a study of this size, the power is insufficient to show a small association or endometriosis might only affect the development of invasive low-grade serous ovarian cancer once serous borderline lesions are already present. Another possible explanation is that several molecular and local environmental factors might give rise to invasive low-grade ovarian cancer and the effect of endometriosis is entirely independent of the association with serous borderline tumours.

 

The definitive confirmation of an association between endometriosis and both clear-cell and endometrioid ovarian cancers fits with the results of molecular studies that have shown the presence of ARID1A gene mutations in 46% of clear-cell and 30% of endometrioid ovarian cancers and in areas of endometriosis that are contiguous with these cancers.8 The molecular basis for a connection with low-grade serous ovarian cancer (which is characterised by mutations in KRAS, BRAF, and ERBB2) has not been defined...............

 

 

Linked Articles

 

Association between endometriosis and risk of histological subtypes of ovarian cancer: a pooled analysis of case–control studies