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Cervicovaginal Microbiome, BRCA1 Mutation Status, and Ovarian Cancer Risk

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Key Points

  • In the ovarian cancer set, women aged ≥ 50 years had a higher prevalence of community type O microbiota compared with those aged < 50 years.
  • In the BRCA set, women with BRCA1 mutations aged < 50 years were more likely to have community type O microbiota vs age-matched controls after adjustment for pregnancy.
  • In both the ovarian cancer set and the BRCA set, younger age was associated with a stronger link between community type O microbiota and ovarian cancer or BRCA1 mutation status.

In a case-control study reported in The Lancet Oncology, Nené et al found that younger women with ovarian cancer or a BRCA1 mutation without cancer were more likely to have cervicovaginal microbiota characterized by a lower (community type O) vs higher (community type L) proportion of species of Lactobacillus. A high proportion of lactobacilli species is associated with a protective low vaginal pH.

The study included two sets of women recruited from sites in the Czech Republic, Germany, Italy, Norway, and the United Kingdom between January 2016 and July 2018. The first of these was an ovarian cancer set (n = 360) consisting of women with epithelial ovarian cancer (n = 176) and controls (n = 184), including both healthy controls (n = 115) and women with benign gynecologic conditions (n = 69). The second was a BRCA set (n = 220) consisting of women with a germline BRCA1 mutation but without ovarian cancer (n = 109) and controls (n = 111) who were wild-type for BRCA1 and BRCA2, including both healthy controls (n = 97) and those with benign gynecologic conditions (n = 14). Cervicovaginal samples from all participants were categorized according to whether lactobacilli accounted for ≥ 50% of cervicovaginal microbiota species (community type L) or < 50% of species (community type O).

Key Findings

In the ovarian cancer set, women aged ≥ 50 years had a higher prevalence of community type O microbiota—61% of 133 ovarian cancer cases and 59% of 142 controls—compared with those aged < 50 years—53% of 43 cases and 29% of 42 controls. In the ovarian cancer set, women aged < 50 years with ovarian cancer had a significantly higher prevalence of community type O microbiota vs age-matched controls (odds ratio [OR] = 2.80, P = .020).

In the BRCA set, women with BRCA1 mutations aged < 50 years were more likely to have community type O microbiota vs age-matched controls after adjustment for pregnancy (OR = 2.79, P = .012). Risk was further increased if more than one first-degree family member was diagnosed with any cancer (OR = 5.26, P = .0022).

In both the ovarian cancer set and the BRCA set, younger age was associated with a stronger link between community type O microbiota and ovarian cancer or BRCA1 mutation status. For example, the OR for community type O for ovarian cancer cases aged < 40 years was 7.00 (P = .025) and the OR for community type O for BRCA1 mutation carriers without cancer aged < 35 years was 4.40 (P = .031).

The investigators concluded, “The presence of ovarian cancer, or factors known to affect risk for the disease (ie, age and BRCA1 germline mutations), were significantly associated with having a community type O cervicovaginal microbiota. Whether reinstatement of a community type L microbiome by using, for example, vaginal suppositories containing live lactobacilli, would alter the microbiomial composition higher up in the female genital tract and in the fallopian tubes, and whether such changes could translate into a reduced incidence of ovarian cancer, needs to be investigated.”

Martin Widschwendter, MD, of the EGA Institute for Women’s Health, University College London, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by EU Horizon 2020 Research and Innovation Programme, EU Horizon 2020 European Research Council Programme, and The Eve Appeal. For full disclosures of the study authors, visit thelancet.com.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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