Variants in the Signaling Protein TSAd are Associated with Susceptibility to Ovarian Cancer in BRCA1/2 Negative High Risk Families.

A substantial fraction of familial ovarian cancer cases cannot be attributed to specific genetic factors. The discovery of additional susceptibility genes will permit a more accurate assessment of hereditary cancer risk and allow for monitoring of predisposed women in order to intervene at the earliest possible stage. We focused on a population with elevated familial breast and ovarian cancer risk. In this study, we identified a SNP rs926103 whose minor allele is associated with predisposition to ovarian but not breast cancer in a Caucasian high-risk population without BRCA1/BRCA2 mutations. We have found that the allelic variation of rs926103, which alters amino acid 52 of the encoded protein SH2D2A/TSAd, results in differences in the activity of this protein involved in multiple signal transduction pathways, including regulation of immune response, tumor vascularization, cell growth, and differentiation. Our observation provides a novel candidate genetic biomarker of elevated ovarian cancer risk in members of high-risk families without BRCA1/2 mutations, as well as a potential therapeutic target, TSAd.

Predictors of decision making in families at risk for inherited breast/ovarian cancer.

OBJECTIVE: The purpose of this study was to identify factors associated with decision making about inherited cancer risk information within families and determine the interdependence between survivors' and relatives' decision making. DESIGN: A descriptive, cross-sectional design using a population-based sample of 146 dyads (N = 292) was used. Analyses included multilevel modeling using the Actor-Partner-Interdependence Model. MAIN OUTCOME MEASURES: Decision making regarding inherited cancer risk information. RESULTS: Several individual and family factors contributed toward survivors' and female relatives' decision making about inherited cancer risk information. Individual factors included the individual's perceptions of their family communication and cancer history. Family factors included survivors' and family members' age, communication and coping style that influenced the decision making of the other member of the dyad. Cancer worries and a monitoring coping style affected both seeking and avoiding decision making for survivors and relatives. CONCLUSIONS: In view of the importance of genetic information upon family health outcomes, it is critical to address both individual and family factors that may influence decision making about cancer risk information and surveillance options for all members within the family.

Risk perception and cancer worries in families at increased risk of familial breast/ovarian cancer.

While families at increased risk for familial breast/ovarian cancer continue to overestimate their cancer risk with increased cancer worries about the future, few studies have examined factors that affect inherited cancer risk perception and cancer worries in both survivors and unaffected female relatives. The purpose of this study was to examine variables that may affect cancer worries and risk perceptions from a family-based perspective in a racially diverse, community-based, random sample of 146 dyads consisting of adult female breast and/or ovarian cancer survivors and their unaffected female relatives (N=292). Results indicated that coping style, self-efficacy, partner's income, family role relationship, and cancer risk perception were significant contributors to the survivors' and their unaffected relatives' cancer worries. Significant variables for perception of cancer risk for both survivors and relatives included income, race, family history of cancer, and cancer worries. Relatives had a higher perception of cancer risk, whereas survivors had more cancer worries. Additionally, the level of cancer worries reported by one member of the dyad was related to the amount of worries reported by the other. The results from this study underscore the importance of clinicians addressing concerns of both affected and unaffected members of families at increased risk of cancer to assist them in managing cancer worries and having realistic risk appraisals to make informed decisions about their own and their family's health surveillance options.

Concerns and recommendations regarding inherited cancer risk: the perspectives of survivors and female relatives.

BACKGROUND: Little research is available comparing differences in cancer risk perceptions between cancer survivors and family members at risk for hereditary breast/ovarian cancer. METHODS: Qualitative focus groups with survivor-female relative dyads (N = 39) were conducted. RESULTS: Important differences exist between the concerns of survivors and family members relevant to their cancer risk. Survivors focused on their own concerns from a personal perspective, whereas family members focused on the survivors' health and tended to suppress their own fears of cancer. Specific recommendations for inclusion of family members in cancer risk education are provided. CONCLUSIONS: Addressing family member differences is critical to tailor specific risk information inclusive of the entire family.

Communication and decision-making about seeking inherited cancer risk information: findings from female survivor-relative focus groups.

Dramatic advances in cancer genetics and identification of germline mutations in cancer genes such as BRCA1 and BRCA2 have led to new options in genetic risk assessment for families with histories of breast and ovarian cancer. However, little research has been carried out with individuals and their families regarding how cancer risk information is communicated within families and factors that may affect individuals and family members making informed decisions about their health. This study explored participants' knowledge of cancer risk, their perceptions and concerns regarding inherited cancer risk information, family communication patterns, and factors that may affect their decision to learn about inherited cancer risk in their families. Nine focus groups of family dyads were conducted (N=39) consisting of breast or ovarian cancer patients and close female relatives. All transcribed interviews were analyzed using qualitative software. Key findings showed diversity in how families communicated and made decisions about their health, persistent worry for their families, lack of knowledge about inherited cancer, vigilance in watching their health, and barriers present in communicating about genetic risk. Results from this study support inclusion of family members in addressing inherited cancer risk information and contextual family factors critical to consider in potentially high risk families.