Ovarian cancer is not one disease — clear cell carcinoma is a distinct, less common histotype, more resistant to standard chemotherapy and more strongly linked to endometriosis. HNF1B, the gene this page's variant sits in, is the most consistently replicated clear-cell-specific susceptibility locus in the literature.
What this condition connects to
Prevalence
Phelan et al. 2017 reported HNF1B as a susceptibility locus specifically for the clear cell histotype of epithelial ovarian cancer, as part of a large international consortium effort (PMID:28346442). The same variant, rs11651755, was separately found associated with endometriosis by Burghaus et al. 2017, who proposed HNF1B as part of the pathway linking endometriosis to ovarian cancer risk (PMID:28214017).
Inheritance
A common variant shifting risk, specific to one ovarian cancer histotype (clear cell) rather than the disease as a whole. Distinct from the rare, high-penetrance BRCA1/BRCA2 mutations that carry much larger risk and are more strongly associated with the high-grade serous histotype.
Epithelial ovarian cancer is not one disease. Its histotypes — high-grade serous (the most common), endometrioid, clear cell, and mucinous — differ enough in cause, behaviour and treatment response that large studies now report genetics separately by histotype rather than pooling everything into one "ovarian cancer" category. Clear cell carcinoma is a smaller, distinct minority of cases: more resistant to standard platinum-based chemotherapy than high-grade serous cancer, and more strongly linked to endometriosis as a clinical precursor.
A consortium-scale confirmation of an already-known locus
Phelan et al. 2017 reported new ovarian cancer susceptibility loci as part of a large international consortium effort, drawing on groups including AOCS, EMBRACE, GEMO, HEBON, KConFab and OPAL. HNF1B, the gene the variant on this page sits in, is catalogued there under the clear cell histotype specifically — consistent with its standing as the most consistently replicated clear-cell-specific ovarian cancer locus in the literature, first identified in earlier, smaller studies and confirmed here at much larger scale.
A second study, and a plausible clinical link
Burghaus et al. 2017 found this same variant, rs11651755 in HNF1B, associated with endometriosis, and proposed HNF1B as part of the biological pathway connecting endometriosis to ovarian cancer risk. This is a mechanistically interesting pairing: endometriosis is already a well-established clinical risk factor specifically for the clear cell and endometrioid histotypes — not for ovarian cancer generally — so a shared genetic locus is a plausible, testable link rather than a coincidence.
Clinical detail
Why the histotype distinction matters clinically
Clear cell ovarian cancer is treated differently from the more common high-grade serous type partly because it responds less well to standard platinum chemotherapy — a clinical fact this variant does not change. Diagnosis and treatment planning rest on histopathology, imaging and clinical staging, not genotype.
A history of endometriosis is a real, established risk factor specifically for clear cell and endometrioid ovarian cancer, and is worth discussing with a gynaecologist regardless of any genetic finding — this variant adds a possible biological explanation for that link rather than a new screening tool.
Related here
Other ovarian cancer variants on this catalogue come predominantly from high-grade serous studies, the more common histotype — a different disease by the standard this page uses, even sharing the same organ.
Related variants MyGeneLog checks for
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about Ovarian Clear Cell Cancer comes down to these specific, well-studied positions — not a diagnosis.
No. Ovarian cancer has several histotypes that differ in cause, behaviour and treatment response. This page is specifically about the clear cell histotype, a smaller and distinct minority of cases.
I have endometriosis. Does this variant mean I will get ovarian cancer?
No. Endometriosis is an established risk factor specifically for clear cell and endometrioid ovarian cancer, and this variant offers one possible genetic link between the two — it does not predict an individual outcome and is not used as a screening tool.
Why is clear cell ovarian cancer treated differently?
It responds less well to standard platinum-based chemotherapy than the more common high-grade serous type, which affects treatment planning. That clinical fact comes from histopathology and treatment response data, not from this variant.
What does HNF1B normally do?
It is a transcription factor with well-established roles elsewhere in biology, including kidney development — mutations in it cause a distinct inherited kidney and diabetes syndrome, unrelated to the common variant on this page. Its specific role in clear cell ovarian cancer risk is an active area of research rather than a settled mechanism.
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