Dataset Information

Familial Ovarian Cancer Clusters with Other Cancers.

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.

SUBMITTER: Zheng G

PROVIDER: S-EPMC6070489 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Familial Ovarian Cancer Clusters with Other Cancers.

Zheng Guoqiao G Yu Hongyao H Kanerva Anna A Försti Asta A Sundquist Kristina K Hemminki Kari K

Scientific reports 20180801 1

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-sp ...[more]

PMID: 30069056

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Project description:Our objective was to determine whether the frequencies of non-ovarian cancers (NOC) within families in a large Familial Ovarian Cancer Registry (FOCR) are significantly different from the frequencies listed in the SEER database. The FOCR was established in 1981. Registry members are families with two or more first degree relatives who have a diagnosis of ovarian cancer, three or more cases of cancer on one side of the family with at least one being ovarian, at least one female with two or more primary cancers in which one is ovary, or a history of two or more cancers in the family with at least one being ovarian cancer diagnosed before the age of 45. The data was analyzed to find relative rates of 10 of the most common cancers found within the database, with the exception of ovarian and breast. These include bladder, CNS, cervical, colorectal, liver, lung, pancreas, prostate, stomach, and uterine. Cancers were further stratified by age at diagnosis, and compared to information in the SEER database. There are 2,671 pedigrees and a total of 50,454 individuals within the FOCR. There are 1,938 families with two or more relatives with ovarian cancer, accounting for 4,816 individuals with ovarian cancer. The total number of individuals with ovarian cancer is 5,421. Of these individuals with ovarian cancer, 2,249 have been verified with testing or physician correspondence. The frequencies of the NOCs within the registry were higher than that of the general population as described in the SEER database. In particular, the overall frequencies of cancers of the bladder, cervix, prostate, and uterus were higher within the FOCR at 2.3, 7.4, 25.2, and 11.9 per 1,000 respectively. Furthermore, diagnoses of both cervical and uterine cancers tended to occur at an earlier age within the FOCR. The overall frequencies of cancers of the bladder, cervix, prostate, and uterus are higher in the FOCR compared with a general population database. Future studies on segregation analysis and genome-wide linkage studies are warranted on families with NOC within the Familial Ovarian Cancer Registry.

Project description:BACKGROUND:Germline mutations in the BRIP1 gene have been described as conferring a moderate risk for ovarian cancer (OC), while the role of BRIP1 in breast cancer (BC) pathogenesis remains controversial. METHODS:To assess the role of deleterious BRIP1 germline mutations in BC/OC predisposition, 6341 well-characterized index patients with BC, 706 index patients with OC, and 2189 geographically matched female controls were screened for loss-of-function (LoF) mutations and potentially damaging missense variants. All index patients met the inclusion criteria of the German Consortium for Hereditary Breast and Ovarian Cancer for germline testing and tested negative for pathogenic BRCA1/2 variants. RESULTS:BRIP1 LoF mutations confer a high OC risk in familial index patients (odds ratio (OR)?=?20.97, 95% confidence interval (CI)?=?12.02-36.57, P?<?0.0001) and in the subgroup of index patients with late-onset OC (OR?=?29.91, 95% CI?=?14.99-59.66, P?<?0.0001). No significant association of BRIP1 LoF mutations with familial BC was observed (OR?=?1.81 95% CI?=?1.00-3.30, P?=?0.0623). In the subgroup of familial BC index patients without a family history of OC there was also no apparent association (OR?=?1.42, 95% CI?=?0.70-2.90, P?=?0.3030). In 1027 familial BC index patients with a family history of OC, the BRIP1 mutation prevalence was significantly higher than that observed in controls (OR?=?3.59, 95% CI?=?1.43-9.01; P?=?0.0168). Based on the negative association between BRIP1 LoF mutations and familial BC in the absence of an OC family history, we conclude that the elevated mutation prevalence in the latter cohort was driven by the occurrence of OC in these families. Compared with controls, predicted damaging rare missense variants were significantly more prevalent in OC (P?=?0.0014) but not in BC (P?=?0.0693) patients. CONCLUSIONS:To avoid ambiguous results, studies aimed at assessing the impact of candidate predisposition gene mutations on BC risk might differentiate between BC index patients with an OC family history and those without. In familial cases, we suggest that BRIP1 is a high-risk gene for late-onset OC but not a BC predisposition gene, though minor effects cannot be excluded.

Dataset Information

Familial Ovarian Cancer Clusters with Other Cancers.

Publications

Familial Ovarian Cancer Clusters with Other Cancers.

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