Female First-degree Relatives Research Articles

Cascade genetic testing (CGT) female first-degree relatives (FDR) of men with germline BRCA2 mutations (gBRCA2mut) and prostate cancer (PCa): A cost-effectiveness analysis.

e17099 Background: g BRCA2mut are associated with increased risk of PCa, breast cancer (BC), and ovarian cancer (OC). ~5% of men with metastatic PCa have g BRCA2mut. CGT is recommended for their relatives as there are implications for cancer prevention and early detection strategies. Little is known about CGT initiated by men with PCa. Here we evaluate the cost-effectiveness of CGT in FDR of men with PCa and g BRCA2mut. Methods: A decision-analytic model was created with TreeAge software to compare BC and OC outcomes for female FDRs who underwent CGT for g BRCA2mut versus no CGT. Our theoretical cohort contained 100,000 females, a conservative estimate of patients who could benefit from CGT. We used literature derived estimates to determine the percentage of patients that would pursue risk-reducing mastectomy, risk-reducing salpingo-oophorectomy, both surgeries, or surveillance after CGT. Outcomes included BC or OC diagnoses, survivorship, and cancer death. We derived all probabilities, costs, utilities, and life expectancies from the literature and discounted quality adjusted life years (QALYs) at a rate of 3%. Incremental cost-effectiveness (ICER) was calculated to determine the cost per QALY gained and set the willingness-to-pay threshold at $100,000/QALY. We assessed the robustness of the model with sensitivity analyses. Results: In our theoretical cohort, CGT of female FDRs resulted in 12,910 less BC diagnoses and 6,360 less BC deaths. CGT was associated with lower BC death rates (26.1%) compared to no CGT (35.8%). OC survival rates were higher with CGT (73.1%) compared to no CGT (36.4%). Our model resulted in lower costs and higher QALYs (a dominant strategy) among the CGT cohort with an ICER of -$7,211.40 per QALY, saving an estimated $595 million. We found that CGT in females was the dominant strategy in 100% of the samples, once uncertainty was incorporated into our model inputs via Monte Carlo simulation. The cost-effectiveness of CGT for male FDRs will be presented at the meeting. Conclusions: In this study, CGT of female FDRs of men with PCa and g BRCA2mut was the dominant strategy to improve BC and OC outcomes, including increased survivorship and reduced BC and OC development. CGT was associated with reduced costs and increased QALYs. CGT for female FDRs of patients with PCa and g BRCA2mut may be a cost-effective approach for identifying and informing individuals with potentially harmful mutations. [Table: see text]

Increased risk of pancreatic, thyroid, prostate and breast cancers in men with a family history of breast cancer: A population-based study.

The association between a family history of breast cancer (FHBC) in female first-degree relatives (FDRs) and cancer risk in men has not been evaluated. This study aimed to compare the risks of overall and site-specific cancers in men with and without FHBC. A population-based study was conducted with 3 329 106 men aged ≥40 years who underwent national cancer screening between 2013 and 2014. Men with and without FHBC in their female FDRs were age-matched in a 1:4 ratio. Men without FHBC were defined as those without a family history of any cancer type in their FDRs. Data from 69 124 men with FHBC and 276 496 men without FHBC were analyzed. The mean follow-up period was 4.7 ± 0.9 years. Men with an FHBC in any FDR (mother or sister) had a higher risk of pancreatic, thyroid, prostate and breast cancers than those without an FHBC (adjusted hazard ratios [aHRs] (95% confidence interval [CI]): 1.35 (1.07-1.70), 1.33 (1.12-1.56), 1.28 (1.13-1.44) and 3.03 (1.130-8.17), respectively). Although an FHBC in any one of the FDRs was not associated with overall cancer risk, FHBC in both mother and sibling was a significant risk factor for overall cancer (aHR: 1.69, 95% CI:1.11-2.57) and increased the risk of thyroid cancer by 3.41-fold (95% CI: 1.10-10.61). FHBC in the mother or sister was a significant risk factor for pancreatic, thyroid, prostate and breast cancers in men; therefore, men with FHBC may require more careful BRCA1/2 mutation-related cancer surveillance.

Risk of estrogen receptor-specific breast cancer by family history of estrogen receptor subtypes and other cancers.

The extent to which the risk of estrogen receptor (ER)-specific breast cancer is associated with ER status of breast cancer and other cancers among first-degree relatives is unclear. This population-based cohort included 464 707 cancer-free women in Stockholm, Sweden, during 1978-2019. For ER-negative and ER-positive breast cancers, we estimated hazard ratios (HRs) associated with ER status of female first-degree relatives with breast cancer and of other cancers in all first-degree relatives. Associations between ER-negative and ER-positive status by family cancer history were estimated using logistic regression in a case-only design. Women with familial ER-positive breast cancer had 1.87 times (95% confidence interval [CI] = 1.77 to 1.97) higher risk of ER-positive subtype, whereas the corresponding hazard ratio for ER-negative was 2.54 (95% CI = 2.08 to 3.10) when having familial ER-negative breast cancer. The risk increased with an increasing number of female first-degree relatives having concordant subtypes and younger age at diagnosis (Ptrend <.001 for both). Nonbreast cancers among first-degree relatives were associated with both ER-positive (HR = 1.14, 95% CI = 1.10 to 1.17) and ER-negative (HR = 1.08, 95% CI = 1.01 to 1.16) breast cancers. Compared with women with ER-positive breast cancer, women with ER-negative breast cancer were more likely to have family history of liver (odds ratio [OR] = 1.33, 95% CI = 1.05 to 1.67), ovary (OR = 1.28, 95% CI = 1.01 to 1.61), and testicle cancer (OR = 1.79, 95% CI = 1.01 to 3.16) but less likely to have family history of endometrial cancer (OR = 0.77, 95% CI = 0.60 to 1.00) and leukemia (OR = 0.72, 95% CI = 0.56 to 0.91). Risk of ER-specific breast cancer differs according to ER status of female first-degree relatives with breast cancer and some other cancers of first-degree relatives. This family history information should be considered in the individual risk prediction for ER subtypes.

Risk of Syndrome-Associated Cancers Among First-Degree Relatives of Patients With Pancreatic Ductal Adenocarcinoma With Pathogenic or Likely Pathogenic Germline Variants

Increased cancer risk in first-degree relatives of probands with pancreatic ductal adenocarcinoma (PDAC probands) who carry pathogenic or likely pathogenic germline variants (PGVs) in cancer syndrome-associated genes encourages cascade genetic testing. To date, unbiased risk estimates for the development of cancers on a gene-specific basis have not been assessed. To quantify the risk of development of PDAC and extra-PDAC among first-degree relatives of PDAC probands who carry a PGV in 1 of 9 cancer syndrome-associated genes-ATM, BRCA1, BRCA2, PALB2, MLH1, MSH2, MSH6, PMS2, and CDKN2A. This case series focused on first-degree relatives of PDAC probands carrying PGVs in specific cancer syndrome-associated genes. The cohort comprised clinic-ascertained patients enrolled in the Mayo Clinic Biospecimen Resource for Pancreas Research registry with germline genetic testing. In total, 234 PDAC probands carrying PGVs were drawn from the prospective research registry of 4562 participants who had undergone genetic testing of cancer syndrome-associated genes. Demographic and cancer-related family histories were obtained by questionnaire. The data were collected from October 1, 2000, to December 31, 2021. For the PDAC probands, the genetic test results of the presence of PGVs in 9 cancer syndrome-associated genes were obtained by clinical testing. Cancers (ovary, breast, uterus or endometrial, colon, malignant melanoma, and pancreas) among first-degree relatives were reported by the probands. Standardized incidence ratios (SIRs) were used to estimate cancer risks among first-degree relatives of PDAC probands carrying a PGV. In total, 1670 first-degree relatives (mean [SD] age, 58.1 [17.8] years; 853 male [51.1%]) of 234 PDAC probands (mean [SD] age, 62.5 [10.1] years; 124 male [53.0%]; 219 [94.4%] White; 225 [98.7%] non-Hispanic or non-Latino]) were included in the study. There was a significantly increased risk of ovarian cancer in female first-degree relatives of probands who had variants in BRCA1 (SIR, 9.49; 95% CI, 3.06-22.14) and BRCA2 (SIR, 3.72; 95% CI, 1.36-8.11). Breast cancer risks were higher with BRCA2 variants (SIR, 2.62; 95% CI, 1.89-3.54). The risks of uterine or endometrial cancer (SIR, 6.53; 95% CI, 2.81-12.86) and colon cancer (SIR, 5.83; 95% CI, 3.70-8.75) were increased in first-degree relatives of probands who carried Lynch syndrome mismatch repair variants. Risk of PDAC was also increased for variants in ATM (SIR, 4.53; 95% CI, 2.69-7.16), BRCA2 (SIR, 3.45; 95% CI, 1.72-6.17), CDKN2A (SIR, 7.38; 95% CI, 3.18-14.54), and PALB2 (SIR, 5.39; 95% CI, 1.45-13.79). Melanoma risk was elevated for first-degree relatives of probands with CDKN2A variants (SIR, 7.47; 95% CI, 3.97-12.77). In this case series, the presence of PGVs in 9 cancer syndrome-associated genes in PDAC probands was found to be associated with increased risk of 6 types of cancers in first-degree relatives. These gene-specific PDAC and extra-PDAC cancer risks may provide justification for clinicians to counsel first-degree relatives about the relevance and importance of genetic cascade testing, with the goal of higher uptake of testing.

Breast Cancer Worry in U.S. Female First-degree Relatives: Moderating Role of Daily Spiritual Experiences.

Female first degree relatives of breast cancer patients experience worry because of their own increased breast cancer risk. The aim in the present study was to examine the role of daily spiritual experiences as a potential protective factor against breast cancer worry. We hypothesized that daily spiritual experiences would moderate the relationship between relatives' stage of disease and breast cancer worry. Sixty-three mothers, daughters or sisters of breast cancer survivors completed surveys assessing relative's disease characteristics and their own demographics, fear of breast cancer, and daily spiritual experiences. All participants were living in the midwestern United States. Results showed that daily spiritual experiences moderated the relationship between stage of disease and breast cancer worry. Low scores on daily spiritual experiences were associated with more worry when relatives had advanced disease, and high scores on daily spiritual experiences was associated with less worry when relatives had advanced disease. Findings suggest the need to focus on this population when providing support services to families of patients.

65 Gene-specific risk of syndrome-associated cancers in first-degree relatives of pancreatic cancer patients with pathogenic/likely pathogenic variants

This abstract is based on unpublished data. OBJECTIVES/GOALS: The estimates of unbiased first-degree relatives (FDRs) risk of cancers would enhance genetic counseling of at-risk FDRs in families where the pancreatic cancer (PC) proband carrying a germline variant. This study aims at quantifying gene-specific risks of six cancers among FDRs of PC patients with germline variants in cancer-associated genes. METHODS/STUDY POPULATION: In the prospective, clinic-based Mayo Clinic Biospecimen Resource for Pancreas Research registry, 4,562 PC patients had previously undergone germline genetic testing for pancreatic cancer-associated genes through either research studies or clinical testing. Of these, 234 PC probands were found to carry germline pathogenic/likely pathogenic variants (PLPV) among 9 genes of interest and had provided detailed demographic and cancer data on their FDRs by questionnaire. We focused on six cancer types (ovary, breast, uterus, pancreas, colon, and malignant melanoma) in FDRs as reported by the probands. Standardized incidence ratios were calculated to estimate risk of six cancers among FDRs of PC patients carrying PLPV by gene. RESULTS/ANTICIPATED RESULTS: 1,670 FDRs (mean age 58.1+17.8SD; 48.9% female) were included in the study. We found significantly increased risk of ovarian cancer in female FDRs of PC probands who carry PLPV in BRCA1 (SIR 9.49, 95%CI:3.06-22.14) or BRCA2 (3.72, 95%CI:1.36-8.11), and breast cancer risks were higher with BRCA2 (2.62, 95%CI:1.89-3.54). Uterine cancer risk was increased in FDRs of PC probands who carry PLPV for Lynch Syndrome mismatch repair (MMR) (6.53, 95%CI:2.81-12.86). PC risk was also increased (ATM 4.53, 95% CI:2.69-7.16; BRCA2 3.45, 95%CI:1.72-6.17; CDKN2A 7.38, 95%CI:3.18-14.54; PALB2 5.39, 95%CI:1.45-13.79). Increased colon cancer risk was observed in FDRs of probands who carried MMR PLPV (5.83, 95%CI:3.70-8.75), while melanoma risk was elevated for FDRs of probands with CDKN2A PLPV (7.47, 95%CI:3.97-12.77). DISCUSSION/SIGNIFICANCE: PLPV in nine syndrome-associated genes in PC probands are associated with increased risk of six cancers in FDRs. The findings underscore the importance of risk estimation of various other cancers in PC families for screening, early detection, intervention, and cascade genetic testing.

Cascade genetic testing (CGT) female first-degree relatives (FDR) of men with germline BRCA2 mutations (gBRCA2mut) and prostate cancer (PCa): A cost-effectiveness analysis.

110 Background: g BRCA2mut are associated with increased risk of PCa, breast cancer (BC), and ovarian cancer (OC). ~5% of men with metastatic PCa have g BRCA2mut. CGT is recommended for their relatives as there are implications for cancer prevention and early detection strategies. Little is known about CGT initiated by men with PCa. Here we evaluate the cost-effectiveness of CGT in FDR of men with PCa and g BRCA2mut. Methods: A decision-analytic model was created with TreeAge software to compare BC and OC outcomes for female FDRs who underwent CGT for g BRCA2mut versus no CGT. Our theoretical cohort contained 100,000 females, a conservative estimate of patients who could benefit from CGT. We used literature derived estimates to determine the percentage of patients that would pursue risk-reducing mastectomy, risk-reducing salpingo-oophorectomy, both surgeries, or surveillance after CGT. Outcomes included BC or OC diagnoses, survivorship, and cancer death. We derived all probabilities, costs, utilities, and life expectancies from the literature and discounted quality adjusted life years (QALYs) at a rate of 3%. Incremental cost-effectiveness (ICER) was calculated to determine the cost per QALY gained and set the willingness-to-pay threshold at $100,000/QALY. We assessed the robustness of the model with sensitivity analyses. Results: In our theoretical cohort, CGT of female FDRs resulted in 12,910 less BC diagnoses and 6,360 less BC deaths. CGT was associated with lower BC death rates (26.1%) compared to no CGT (35.8%). CGT was not associated with reduction in OC diagnoses or deaths. Our model resulted in lower costs and higher QALYs (a dominant strategy) among the CGT cohort with an ICER of -$4,190.10 per QALY, saving an estimated $595 million. We found that CGT in females was the dominant strategy in 100% of the samples, once uncertainty was incorporated into our model inputs via Monte Carlo simulation. The cost-effectiveness of CGT for male FDRs will be presented at the meeting. Conclusions: In this study, CGT of female FDRs of men with PCa and g BRCA2mut was the dominant strategy to improve BC outcomes, including increased survivorship and reduced BC development. Despite a lack of demonstrated benefit for OC, CGT was associated with reduced costs and increased QALYs. CGT for female FDRs of patients with PCa and g BRCA2mut may be a cost-effective approach for identifying and informing individuals with potentially harmful mutations. [Table: see text]

Frequency of hirsutism in patients with PCOS (polycystic ovary syndrome)

Objective: To estimate the prevalence of PCOS, a clinically noticeable disorder in women that causes excessive development of coarse or dark hair on the face, chest, and back in a male-like pattern, between first-degree female relatives in families with a proband who has the condition. Methods: A history of oligomenorrhea, hirsutism or biochemical proof of hyperandrogenism (raised entire or free T) and other illnesses were used to diagnose PCOS. Moreover, for better results, Study participants through PCOS (age 24.3G5.8 years, Body Mass Index 26.8G6.9 kg/m2) were used for better results. An R8-modified Ferriman-Gallwey score was used to characterize hirsutism. Results: 24% of the mothers and 32% of the sisters among the moms and sisters assessed had PCOS, respectively. Only premenopausal women who were not receiving treatment i.e., moms (35%) and sisters (40%) for PCOS were found to have the condition, which is consistent with symptoms becoming better due to hormone therapy or age. These PCOS prevalence percentages are much greater than the illness's frequency in the normal community (about 4%), which points to a considerable hereditary component. Furthermore, in comparison to female without hirsutism, hirsute female were pretty young, had greater BMIs, and also had greater amounts of circulatory androgens.

Family coaggregation of type 1 diabetes mellitus, major depressive disorder, attention-deficiency hyperactivity disorder and autism spectrum disorder in affected families: a nationwide study.

This study aimed to examine the risk of T1D, major depressive disorder (MDD), attention-deficiency hyperactivity disorder (ADHD), and autism spectrum disorder (ASD), in first-degree relatives (FDRs) of patients with T1D. We enrolled 24,555 FDRs of individuals with T1D and 1:4 matched controls (N = 98,220) based on age and sex using data from the Taiwan National Health Insurance Research Database between 2001 and 2011. Poisson regression analyses were performed to estimate the risks of MDD, attention-deficiency hyperactivity disorder (ADHD), and autism spectrum disorder among the FDRs. Finally, we assessed the impact of DKA in the familial coaggregation. After adjusting for demographic characteristics, FDRs of individuals with T1D had higher risk of T1D (reported as relative risk with 95% confidence interval: 46.07, 33.36-63.63) and MDD (1.17, 1.04-1.32) than controls. Stratified by sex, female FDRs had increased risk of MDD (1.30, 1.13-1.51), while male FDRs had increased risk of ADHD (1.21, 1.01-1.44). Stratified by kinship, parents of individuals with T1D had increased risk of MDD (1.24, 1.06-1.44); offspring of individuals with T1D had increased risk of ADHD (1.41, 1.11-1.79). Importantly, FDRs of individuals with T1D and DKA had higher risk of MDD (1.35, 1.11-1.64) and ADHD (1.40, 1.07-1.82) than controls; however, such risks were not observed in FDRs of individuals with T1D but without DKA. The individual risks of T1D, MDD, and ADHD were increased in families that included patients with T1D, and DKA might play a role in such coaggregation with MDD and ADHD. Future studies are warranted to investigate the underlying mechanisms.

Abstract A033: Gene-specific risk of syndrome-associated cancers in first-degree relatives of pancreatic cancer patients with pathogenic/likely pathogenic variants

Abstract Increased pancreatic cancer (PC) risk in first-degree relatives (FDRs) of PC patients with germline pathogenic/likely pathogenic variants (PLPV) is a motivator for cascade genetic testing. To date, unbiased FDR risk estimates for gene-specific risks of genetic cancer syndrome-associated cancers are unknown. These estimates would enhance genetic counseling of at-risk FDRs in families where the PC proband has been found to carry a PLPV. Study Aim: To objectively quantify gene-specific risks of six relevant cancers among FDRs of PC patients with germline PLPV in ATM, BRCA1, BRCA2, CDKN2A, MLH1, MSH2, MSH6, PALB2, and PMS2. Methods: In the prospective, clinic-based Mayo Clinic Biospecimen Resource for Pancreas Research registry, 4,562 PC patients had previously undergone germline genetic testing for pancreatic cancer-associated genes through either research studies or clinical testing. Of these, 234 PC probands were found to carry PLPV among 9 genes of interest and had provided detailed demographic and cancer data on their FDRs by questionnaire. We focused on six cancer types (ovary, breast, uterus, pancreas, colon, and malignant melanoma) in FDRs as reported by the probands. Standardized incidence ratios estimated risk by gene of six cancers among FDRs of PC patients carrying PLPV. Results: 1,670 FDRs (mean age 58.1+17.8SD; 48.9% female) were included in the study. We found significantly increased risk of ovarian cancer in female FDRs of PC probands who carry PLPV in BRCA1 (SIR 9.49, 95%CI:3.06-22.14) or BRCA2 (3.72, 95%CI:1.36-8.11), and breast cancer risks were higher with BRCA2 (2.62, 95%CI:1.89-3.54). Uterine cancer risk was increased in FDRs of PC probands who carry PLPV for Lynch Syndrome mismatch repair (MMR) (6.53, 95%CI:2.81-12.86). PC risk was also increased (ATM 4.53, 95% CI:2.69-7.16; BRCA2 3.45, 95%CI:1.72-6.17; CDKN2A 7.38, 95%CI:3.18-14.54; PALB2 5.39, 95%CI:1.45-13.79). Increased colon cancer risk was observed in FDRs of probands who carried MMR PLPV (5.83, 95%CI:3.70-8.75), while melanoma risk was elevated for FDRs of probands with CDKN2A PLPV (7.47, 95%CI:3.97-12.77). Conclusion: PLPV in nine syndrome-associated genes in PC probands are associated with increased risk of six cancers in FDRs in PC families. The findings underscore the importance of risk estimation of various other cancers in PC families for screening, early detection, and intervention. The gene-specific quantified cancer risks for FDRs of PC patients with syndrome-associated germline PLPV can inform counseling regarding extra-PC risks when considering cascade genetic testing. Citation Format: Xuan Chen, Kari Rabe, Margaret Meyer, Jennnifer Kemppainen, Masayasu Horibe, Shruti Chandra, Shounak Majumder, Gloria Petersen. Gene-specific risk of syndrome-associated cancers in first-degree relatives of pancreatic cancer patients with pathogenic/likely pathogenic variants [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr A033.

Fibromuscular Dysplasia and Abdominal Aortic Aneurysms Are Dimorphic Sex-Specific Diseases With Shared Complex Genetic Architecture.

The risk of arterial diseases may be elevated among family members of individuals having multifocal fibromuscular dysplasia (FMD). We sought to investigate the risk of arterial diseases in families of individuals with FMD. Family histories for 73 probands with FMD were obtained, which included an analysis of 463 total first-degree relatives focusing on FMD and related arterial disorders. A polygenic risk score for FMD (PRSFMD) was constructed from prior genome-wide association findings of 584 FMD cases and 7139 controls and evaluated for association with an abdominal aortic aneurysm (AAA) in a cohort of 9693 AAA cases and 294 049 controls. A previously published PRSAAA was also assessed among the FMD cases and controls. Of all first degree relatives of probands, 9.3% were diagnosed with FMD, aneurysms, and dissections. Aneurysmal disease occurred in 60.5% of affected relatives and 5.6% of all relatives. Among 227 female first-degree relatives of probands, 4.8% (11) had FMD, representing a relative risk (RR)FMD of 1.5 ([95% CI, 0.75-2.8]; P=0.19) compared with the estimated population prevalence of 3.3%, though not of statistical significance. Of all fathers of FMD probands, 11% had AAAs resulting in a RRAAA of 2.3 ([95% CI, 1.12-4.6]; P=0.014) compared with population estimates. The PRSFMD was found to be associated with an AAA (odds ratio, 1.03 [95% CI, 1.01-1.05]; P=2.6×10-3), and the PRSAAA was found to be associated with FMD (odds ratio, 1.53 [95% CI, 1.2-1.9]; P=9.0×10-5) as well. FMD and AAAs seem to be sex-dimorphic manifestations of a heritable arterial disease with a partially shared complex genetic architecture. Excess risk of having an AAA according to a family history of FMD may justify screening in family members of individuals having FMD.

Returning individual genomic results to population-based cohort study participants with BRCA1/2 pathogenic variants.

Recent advances in human genome research have provided evidence for genotype-phenotype associations, pathogenicity, and clinical actionability of variants and genomic risk prediction of disease. However, the return of individual genomic results to healthy individuals is fraught with ethical and practical complexity. Individual genomic results were returned to BRCA1/2 pathogenic variant (PV) carriers of the Tohoku Medical Megabank cohort study participants with an information on hereditary breast and ovarian cancer syndrome (HBOC). One hundred and eighty participants, including 9 BRCA1/2 PV carriers, were asked about their willingness to receive individual genomic results, without revealing the gene name and related disorders, prior to the study. Of the 142 participants who responded, 103 showed willingness to know their genomic information. Each of the six BRCA1/2 PV carriers who consented to participate in the study received information about HBOC in person and underwent validation testing with blood resampling. All participants were in their 60s or 70s; of the four females and two males, two had a history of breast cancer and five had a family history of HBOC-related cancers. All participants appreciated the information, without remarkable negative psychological impact of the return, and intended to undergo clinical risk surveillance. Five participants were accompanied by family members while receiving the results, and three first-degree female relatives wished to undergo genomic testing at the hospital. Our results suggest that returning actionable genomic information to participants in a population-based genome cohort study is beneficial for preventing or providing early-stage intervention for associated diseases.

Motivation and family communication in hereditary prostate cancer genetic testing: Survey of patients from a US tertiary medical center.

Identification of a hereditary prostate cancer in an affected individual can guide treatment and may also impact cancer screening and surveillance for patients and their relatives. This study aimed to determine the factors that are associated with the decision-making process of individuals with prostate cancer regarding whether to pursue genetic testing as well as how, why, and with whom genetic test results are shared. We surveyed 113 patients diagnosed with prostate cancer who received cancer genetic counseling through a United States tertiary medical center, inquiring about genetic testing motivations and family communication about results. Among those who pursued genetic testing, (1) learning about my family's possible cancer risk (98%), (2) learning information that may guide cancer treatment (93%), and (3) learning if I am at risk for future cancers (92%) were most frequently identified as slightly or very important factors in their decision. Participants shared their genetic test results in a higher proportion to male first-degree relatives than female first-degree relatives; however, no significant difference was found (p=0.103). Our study may suggest sex differences related to family communication about genetic testing results. Such findings indicate a critical need for genetic counselors to clearly communicate the impact of genetic test results on both male and female relatives. Further research on motivation and family communication about genetic test results in diverse cohorts is needed.

Ovarian cancer risk of Chinese women with BRCA1/2 germline pathogenic variants

Estimating the lifetime risk of ovarian cancer in Chinese women with BRCA1/2 germline pathogenic variants (PVs) is of great importance for the clinical management of BRCA1/2 carriers. This cohort study recruited 9903 unselected Chinese breast cancer patients whose BRCA1/2 status was determined. Of these, 3984 probands completed family history questionnaires, which investigated the health status of their relatives, including 11,997 female first-degree relatives. The ovarian cancer risk of BRCA1/2 germline pathogenic carriers was estimated using the ovarian cancer history of proband first-degree female relatives via the Kin-cohort method. Of the 3984 probands, 126 (3.2%) carried BRCA1 PVs, and 183 (4.6%) carried BRCA2 PVs. The estimated cumulative risks of ovarian cancer by age 70 were 15.3% (95% CI 8.4-18.6%) for BRCA1 carriers, 5.5% (95% CI 2.0-10.2%) for BRCA2 carriers, and 0.4% (95% CI 0.3-0.7%) for noncarriers. The cumulative risks of ovarian cancer were very low before the age of 40 for both BRCA1 and BRCA2 carriers and were an increase up to age 45. The cumulative ovarian cancer risk of BRCA1 carriers was approximately three times higher than that of BRCA2 carriers, and BRCA1 and BRCA2 carriers had 38- and 14-fold higher risks than non-BRCA carriers, respectively. The findings indicate that Chinese women with BRCA1/2 PVs have high risks of ovarian cancer in their lifetime, especially BRCA1 carriers. These results are useful for devising optimal strategies to reduce ovarian cancer risk in BRCA1/2 carriers.

Associations of a family history of lupus with the risks of lupus and major psychiatric disorders in first-degree relatives.

Genetic factors link psychiatric disorders, particularly major depressive disorder (MDD), bipolar disorder, and obsessive-compulsive disorder (OCD), with systemic lupus erythematosus (SLE). Additionally, maternal SLE is a risk factor for long-term developmental problems, particularly learning disabilities, attention disorders, autism spectrum disorder (ASD) and speech disorders, in children. We aimed to determine whether first-degree relatives (FDRs) of patients with SLE have increased risks of SLE and major psychiatric disorders. Using the Taiwan National Health Insurance Research Database, we recruited 40 462 FDRs of patients with SLE as well as 161 848 matched controls. The risks of major psychiatric disorders, including schizophrenia, bipolar disorder, OCD, MDD, ASD and attention-deficit/hyperactivity disorder (ADHD), were assessed. The FDRs of patients with SLE had higher risks of SLE (reported as the adjusted relative risk and 95% confidence interval: 14.54; 12.19-17.34), MDD (1.23; 1.12-1.34), ADHD (1.60; 1.55-1.65), OCD (1.41; 1.14-1.74) and bipolar disorder (1.18; 1.01-1.38) compared with controls. Specifically, male FDRs of patients with SLE had higher risks of SLE and bipolar disorder, whereas female FDRs of patients with SLE had higher risks of MDD and OCD. Differences in the familial relationship (i.e. parents, children, siblings and twins) were consistently associated with higher risks of these disorders compared with controls. The FDRs of patients with SLE had higher risks of SLE, MDD, ADHD, OCD and bipolar disorder than the controls.

Perceived risk and risk reduction behaviours of female first-degree relatives of breast cancer patients attending care at Uganda cancer institute.

The objective of this study was to assess the perceived risk of breast cancer (BC) and adoption of risk reduction behaviours among female first-degree relatives (FDRs) of BC patients attending care at the Uganda Cancer Institute (UCI). A cross-sectional study was performed using a questionnaire to collect data between March to October 2019. Adult female FDRs of patients attending care at UCI were recruited consecutively. Breast cancer perceived risk was assessed using a verbal measure; 'My chances of getting BC are great' on a Likert scale with 5 response alternatives. Chi square tests and modified Poisson regression using generalised estimating equations model were used to determine associations and examine factors associated with perceived risk of BC. We enrolled 296 FDRs from 186 female BC patients. Few participants 118/296 (40%) had high perceived risk of BC. Majority 165/296 (56%), had ever practiced breast self-examination. At the multivariable modified Poisson GEE model, women aged 36-45years were more likely to perceive themselves to be at high risk of developing BC compared to women aged 18-25years (adjusted prevalence ratio: 1.174; 95% confidence interval [95%CI]=1.05-2.88; p value=0.030) after adjusting for age, religion, educational level and residence. Few FDRs of BC patients perceived themselves to be at high risk of developing BC and do not seek risk reduction measures including screening and early diagnosis approaches. Breast cancer health education especially targeting younger women should emphasize the increased risk of BC in FDRs.

PEACE-S risk coping: A qualitative study exploring protective behavioral strategies of first-degree relatives of breast cancer survivors.

Breast cancer is a major cause of morbidity worldwide and first-degree relatives of breast cancer survivors have a significantly higher risk of breast cancer that can be reduced by altering controllable risk factors. This study examined protective behavioral strategies used to cope with the risk in female first-degree relatives based on descriptions of their experiences, as well as their reason(s) for choosing a particular coping strategy. A total of 25 first-degree relatives of breast cancer survivors in 13 families were recruited for this descriptive qualitative study. Data were collected between January and November 2020 through individual interviews, and a thematic analysis was performed using MAXQDA software. Three themes under an overarching theme of 'competition with breast cancer risk' were identified: (1) protective behavioral strategies for coping with breast cancer risk (four coping types); (2) barriers and facilitators for behavior change (five unfavorable and favorable factors related to the type of coping); and (3) significant determinants of coping strategy types. Based on these three themes, we developed a Personal restrictions, Exposure hazards, Adverse circumstances, Coping ability, Endorsement from social network, and Significant determinants ('PEACE-S') scale model of first-degree relatives' strategies for coping with breast cancer risk. First-degree relatives present different risk coping strategies that are shaped by individual and external factors and specific determinants. Our results provide insights that can help healthcare professionals design targeted interventions based on first-degree relatives' individual circumstances to mitigate breast cancer risk in this group through the adoption of healthy lifestyle choices.

Clinicopathological Characteristics of Prostate Cancer in Tlemcen (Northwestern Algeria)

Background: Prostate cancer is the main cause of cancer death in men in about 48 countries, including several sub-Saharan African, Caribbean, Central and South American countries. Despite the prevalence of prostate cancer, little is known about its etiology. Limited data exist for North Africa, and Algeria in particular, at the crossroads of Sub-Saharan Africa, the Middle East, southern Europe, and the Mediterranean region. Objective: This study aimed to determine the relationship between a family history of cancer and age at diagnosis, and to assess the effect of a family history of cancer and prostate-specific antigen (PSA) levels on tumor prognosis. Methods: This cross-sectional study was conducted on the records of 184 patients with prostate cancer confirmed by biopsy, diagnosed between 2011 and 2016 at the Urology Division of Tlemcen’s teaching hospital. The collected data included the age at diagnosis, PSA level on presentation, Gleason score on biopsy, and a family history of cancer. Univariate statistical analyses were performed using ANOVA, independent-samples t-test, and Fisher's exact test in Minitab® 17. Results: Men who had first-degree female relatives with breast cancer had a younger mean age at diagnosis (67.31 y) than those who did not have the same family history (72.3 y) (p=0.02). Positive first-degree family history for prostate cancer was associated with favorable tumor prognosis (Gleason ≤ 6) at the time of diagnosis (p&lt;0.001). There was also a significant moderate positive correlation (Pearson correlation = 0.35) between PSA level and Gleason score (p&lt;0.001). Conclusion: Our data suggest an association between positive first-degree family history for breast/prostate cancer and the age of onset. Positive first-degree family history for prostate cancer appears to predict a favorable tumor prognosis. The Gleason score seems to rise with the PSA level. Men with a family history of prostate/breast cancer might start prostate cancer screening earlier than those without the same family history. This study raises several questions that need to be addressed in future research. Prospective cohort studies would help identify and assess ethnic, genetic, hormonal, and environmental risk factors, and investigate the interactions influencing the genesis of this cancer, thereby guiding public health plans for cancer control and intervention strategies (screening, treatment, and survivor care).

Evaluating the Effect of Health Education Intervention on the Health Beliefs and Behaviors of First-Degree Female Relatives of Breast Cancer Patients.

Sule OlgunBackground Breast cancer risk increases by 80% in the presence of BRCA1 and BRCA2 gene mutations in the same family. In particular, a woman whose sister or mother has breast cancer has a 2- to 5-fold higher risk of developing breast cancer compared with other women. For this reason, recommendations should have been made regarding breast cancer prevention and/or early detection for women with first-degree family history of breast cancer. Aim The aim of this study was to evaluate the effect of health education, which was provided to first-degree female relatives of breast cancer patients, on their health beliefs and behaviors. Study Design and Methods The study sample included 50 women with a first-degree relative being treated for breast cancer in the chemotherapy and radiotherapy unit of a university hospital. A one-group pretest-posttest design was used. The pretest consisted of the health belief model scale and a questionnaire regarding the women's sociodemographic information and breast cancer screening behaviors. After the pretest, the patients received health education regarding breast cancer risk factors and screening methods. The posttest was conducted 3 weeks after the education using the same assessment tools. Results After education, there were statistically significant increases in rates of practicing breast self-examination, having clinical breast examinations, and undergoing breast ultrasound/mammography compared with pretest results. Conclusions Health workers should possess knowledge and experience about breast cancer which will enable them to effectively undertake an educational role, especially for high-risk groups such as women with first-degree family history of breast cancer.

Profile of Daughters and Sisters of Women With Polycystic Ovary Syndrome: The Role of Proband's Glucose Tolerance.

First-degree relatives of women with polycystic ovary syndrome (PCOS) present hormonal and metabolic alterations compared to girls unrelated to PCOS. It is unknown whether glucose intolerance in the PCOS proband confers a more severe metabolic predisposition on their first-degree relatives. To determine whether glucose tolerance status in women with PCOS is associated with worsened glucose metabolism and sex hormone levels in their peripubertal daughters or sisters. Cross-sectional study. Seven academic centers in North America, South America, and Europe. Sixty-four pairs of women with PCOS and their daughters or younger sisters aged between 8 and 14 years were recruited. Twenty-five mothers or older sisters with PCOS were glucose intolerant (GI) and 39 were normal glucose tolerant (NGT). Beta-cell function estimated by the insulin secretion-sensitivity index-2 (ISSI-2) during an oral glucose tolerance test and by the disposition index during a frequently sampled IV glucose tolerance test. Free testosterone and 17-hydroxyprogesterone (17-OHP) levels. Being related to a GI PCOS proband was associated with a lower ISSI-2 (P-value = 0.032) after adjusting for ethnicity, body mass index z-score, and pubertal stage. They also had higher free testosterone (P-value = 0.011) and 17-OHP levels compared to girls with an NGT proband, the latter becoming significant after adjusting for confounders (P-value = 0.040). Compared to first-degree female relatives of women with PCOS and NGT, first-degree relatives of women with PCOS and GI display lower beta-cell function and hyperandrogenemia, putting them at higher risk of GI and PCOS development.