Abstract
Familial risk of ovarian cancer is well-established but whether ovarian cancer clusters with other cancers and the clusters differ by histology remains uncertain. Using data from the Swedish Family-Cancer Database, we explored familial associations of ovarian cancer with other cancers with a novel approach; relative risk for (histology-specific) ovarian cancer was estimated in families with patients affected by other cancers, and conversely, risks for other cancers in families with (histology-specific) ovarian cancer patients. Eight discordant cancers were associated with ovarian cancer risk, of which family history of breast cancer showed a dose-response (P-trend <0.0001). Conversely, risks of eight types of cancer increased in families with ovarian cancer patients, and dose-responses were shown for risks of liver (P-trend = 0.0083) and breast cancers (P-trend <0.0001) and cancer of unknown primary (P-trend = 0.0157). Some cancers were only associated with histology-specific ovarian cancers, e.g. endometrial cancer was only associated with endometrioid type but with highest significance. Novel associations with virus-linked cancers of the nose and male and female genitals were found. The results suggest that ovarian cancer shares susceptibility with a number of other cancers. This might alert genetic counselors and challenge approaches for gene and gene-environment identification.
Highlights
Ovarian cancer is a heterogeneous disease commonly classified into epithelial and non-epithelial types
It is well-known that family history of ovarian cancer is associated with increased ovarian cancer risk and the relative risk is estimated to be 2.0 to 4.0 when having a first-degree relative affected by ovarian cancer[4,5,6,7,8]
Relative risks (RRs) is calculated for ovarian cancer (OC); person-years at risk are calculated for all persons in the offspring generation; probands are all first-degree relatives with cancer X
Summary
Ovarian cancer is a heterogeneous disease commonly classified into epithelial and non-epithelial types. For example,patient with high-grade serous ovarian carcinoma always has poor prognosis compared to other types because most patients (∼80%) present with advanced stage at diagnosis[1]. It is well-known that family history of ovarian cancer is associated with increased ovarian cancer risk and the relative risk is estimated to be 2.0 to 4.0 when having a first-degree relative affected by ovarian cancer[4,5,6,7,8]. The aim of our present study was to explore the familial associations of histology-specific ovarian cancer with other discordant cancers using multiple independent analyses for reliable results. Our results should be relevant for genetic counseling, precise treatment and health care for patients with ovarian cancer and may provide clues about shared genetic and/or environmental risk factors
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