TY  - GEN
TI  - Breast and ovarian cancers in women: familial clustering, second primary cancer and cause of death
UR  - https://archiv.ub.uni-heidelberg.de/volltextserver/26949/
N2  - Female cancers account for 44% of cancer diagnoses in women globally, among which breast cancer is the most frequently diagnosed cancer and ovarian cancer is a relatively fatal disease. Familial clustering of these two cancers with the same (concordant) cancer is well established, but whether they cluster with other (discordant) cancers is less studied. How cancer family history impacts on risk of this cancer as second primary cancer (SPC) in breast and ovarian cancers and the related cause of death are also interesting questions for the fact that the cancer survival increases in recent years. Hence, this study is to analyze the familial clustering of breast and ovarian cancer with the concordant and discordant cancers as well as familial risk of SPC and related cause of death in breast and ovarian cancer patients.
Based on the Swedish Family-Cancer Database, the risks of breast and ovarian cancers when their first-degree relatives were diagnosed with the concordant and discordant cancers and the risks of other cancers when first-degree relatives were diagnosed with breast and ovarian cancers were estimated. The cancer risks were also stratified by sex and histology. In the analysis for the impact of family history on the risk of second primary cancer, the risk of SPC with family history of the same cancer was compared to that without family history. Cause of death in those patients was analyzed based on the diagnosis of second primary cancer. ICD-7 was used to identify cancers and SNOMED was to histology. Poisson regression model was performed for risk estimation and calculation of their corresponding CIs for 95%, 99% and 99.9%. 
The familial risks of breast and ovarian cancers with the concordant cancer family history are high for early-onset patients and those with multiple affected relatives and familial risk varies among histological types. Breast cancer shares susceptibility with a group of other cancers for which gene-environment interactions with hormonal and immunological pathways could be involved and ovarian and prostate cancers showed most significant associations. Some novel associations of breast cancer were found with female kidney and bladder cancers and with myeloma.  We observed that ovarian cancer was associated with a group of discordant cancers and among them colorectal, breast, endometrial and liver cancers and CUP showed significance in the two-way analysis. The novel associations with cancer of nose and that of male and female genitals were noted.
For breast cancer patients in families with individuals diagnosed with cancer, 18.3% of non-breast SPCs were due to family history. Prominent familial risks were found in cancers that share genetic, reproductive or behavioral factors with breast cancer. For ovarian cancer patients, high familial risks were found for breast and colorectal cancers, which are known to manifest in ovarian cancer-related syndromes. However, family history of a particular cancer contributed to the elevated risk of SPC in ovarian cancer patients at the same site regardless of the non-inclusion of possible high-risk families. SPC was the main cause of death in the breast and ovarian cancer patients with SPCs.
Our study suggested that family history may indicate the possible familial clustering with genetic background, for which different cancers may aggregate in different family members or in one individual presenting as multiple primary cancers, which provide useful information on genetic counseling and disease management.
ID  - heidok26949
AV  - public
A1  - Zheng, Guoqiao
Y1  - 2019///
ER  -