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1.
Menopause ; 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31644510

RESUMO

OBJECTIVE: BRCA mutation carriers are advised to undergo bilateral salpingo-oophorectomy to prevent ovarian cancer. The abrupt hormonal withdrawal associated with early surgical menopause has been shown to increase the risk of depression and anxiety among women in the general population. The impact in women with a BRCA1 or BRCA2 mutation is not known. METHODS: We undertook a matched prospective study of BRCA mutation carriers to evaluate the impact of oophorectomy on self-reported initiation of antidepressant use. We identified women with no personal history of cancer or depression and prospectively evaluated the frequency of self-reported medication use after surgery. Each exposed participant (oophorectomy) was randomly matched to a control participant (no oophorectomy) according to year of birth (within 3 years), BRCA mutation type (BRCA1 or BRCA2), and country of residence (Canada, United States, Poland). A total of 506 matched sets were included. We estimated the odds ratio (OR) and 95% confidence intervals (CIs) of antidepressant use (ever/never) following preventive oophorectomy in the entire study population and stratified by age at oophorectomy and by use of hormone therapy. RESULTS: Oophorectomy was not associated with more frequent antidepressant use among BRCA mutation carriers (OR = 0.46; 95% CI 0.22-0.96). We observed reductions in the odds of antidepressant medication use among women who underwent oophorectomy before the age of 50 years (OR = 0.33; 95% CI 0.14-0.78) and among those who initiated hormone therapy use after oophorectomy (OR = 0.35; 95% CI 0.14-0.90). Findings were similar when the analysis was based on self-reported depression (rather than antidepressant use). CONCLUSIONS: Although based on a small number of women, these findings suggest that oophorectomy does not increase psychological distress among women at an elevated risk of ovarian cancer.

2.
Genet Med ; 2019 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-31204389

RESUMO

PURPOSE: Biallelic pathogenic variants in the mismatch repair (MMR) genes cause a recessive childhood cancer predisposition syndrome known as constitutional mismatch repair deficiency (CMMRD). Family members with a heterozygous MMR variant have Lynch syndrome. We aimed at estimating cancer risk in these heterozygous carriers as a novel approach to avoid complicated statistical methods to correct for ascertainment bias. METHODS: Cumulative colorectal cancer incidence was estimated in a cohort of PMS2- and MSH6-associated families, ascertained by the CMMRD phenotype of the index, by using mutation probabilities based on kinship coefficients as analytical weights in a proportional hazard regression on the cause-specific hazards. Confidence intervals (CIs) were obtained by bootstrapping at the family level. RESULTS: The estimated cumulative colorectal cancer risk at age 70 years for heterozygous PMS2 variant carriers was 8.7% (95% CI 4.3-12.7%) for both sexes combined, and 9.9% (95% CI 4.9-15.3%) for men and 5.9% (95% CI 1.6-11.1%) for women separately. For heterozygous MSH6 variant carriers these estimates are 11.8% (95% CI 4.5-22.7%) for both sexes combined, 10.0% (95% CI 1.83-24.5%) for men and 11.7% (95% CI 2.10-26.5%) for women. CONCLUSION: Our findings are consistent with previous reports that used more complex statistical methods to correct for ascertainment bias. These results underline the need for MMR gene-specific surveillance protocols for Lynch syndrome.

3.
J Health Commun ; 24(4): 377-384, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31060454

RESUMO

Refined estimates of risk based on genetic risk modifiers could assist BRCA mutation carriers in understanding their risk, but it is not clear whether carriers are interested in receiving these estimates or how they might benefit from them. Using qualitative interviews, we investigated female BRCA1 and BRCA2 mutation carriers' (N = 20) reactions to numerical and verbal presentations of breast cancer risk based on risk modifiers and assessed women's preferences regarding visual formats for communicating risk. Our results show carriers are interested in receiving refined risk estimates and suggest the estimates may influence decision-making regarding cancer prevention, depending on the nature of the risk assessment. Although accurate and precise estimates of breast cancer risk are most important to women, they preferred quantitative risk estimates expressed as a proportion with or without a population comparison; however, women noted that comparisons to other BRCA mutation carriers were less useful given their high risk. Participants also preferred communication of a risk as a specific percentage versus a range of risk, but a clear preference regarding visual displays was not expressed. Results support many existing recommendations for genetic risk communication and provide guidance for the development of tools incorporating genetic risk modifiers.

4.
Br J Cancer ; 121(1): 15-21, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30971774

RESUMO

BACKGROUND: Women with a BRCA1 or BRCA2 mutation face high risks of breast and ovarian cancer. In the current study, we report on uptake of cancer screening and risk-reduction options in a cohort of BRCA mutation carriers from ten countries over two time periods (1995 to 2008 and 2009 to 2017). METHODS: Eligible subjects were identified from an international database of female BRCA mutation carriers and included women from 59 centres from ten countries. Subjects completed a questionnaire at the time of genetic testing, which included past use of cancer prevention options and screening tests. Biennial follow-up questionnaires were administered. RESULTS: Six-thousand two-hundred and twenty-three women were followed for a mean of 7.5 years. The mean age at last follow-up was 52.1 years (27-96 years) and 42.3% of the women had a prior diagnosis of breast cancer. In all, 27.8% had a prophylactic bilateral mastectomy and  64.7% had a BSO. Screening with breast MRI increased from 70% before 2009 to 81% at or after 2009. There were significant differences in uptake of all options by country. CONCLUSION: For women who received genetic testing more recently, uptake of prophylactic mastectomy and breast MRI is significantly higher than those who received genetic testing more than 10 years ago. However, uptake of both BSO and breast MRI is not optimal, and interventions to increase uptake are needed.

5.
J Genet Couns ; 28(3): 664-672, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30843639

RESUMO

Pathogenic germline mutations in the BRCA1 or BRCA2 genes are associated with an elevated lifetime risk for breast (50%-85% risk) and ovarian cancer (20%-40% risk). Genome-wide association studies have identified over 100 genetic variants associated with modified breast and/or ovarian cancer risk in BRCA1 and BRCA2 carriers. Risk models generated based on these variants have shown that these genetic modifiers strongly influence absolute risk of developing breast or ovarian cancer in BRCA mutation carriers. There is a lack of understanding, however, about the clinical applicability and utility of these risk models. To investigate this gap, we collected survey data from 274 cancer genetic counselors (GCs) through the National Society of Genetic Counselors Cancer Special Interest Group. Questions assessed perceptions of usefulness and intentions of genetic counselors to use these refined risk models in clinical care based on the Technology Acceptance Model (TAM). We found that GCs' reactions to the estimates were largely positive, though they thought the possibility of changing management based on results was unlikely. Additionally, we found that more experienced GCs were more likely to consider refined risk estimates in clinic. Support also was provided for core predictions within the TAM, whereby the perceived usefulness (indirect effect est. = 0.08, 95% CI: [0.04, 0.13]) and perceived ease of use (indirect effect est. = 0.078, 95% CI: [0.04, 0.13]) of refined risk estimates were indirectly associated with intentions to use via attitudes.

6.
Breast Cancer Res Treat ; 175(2): 443-449, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30756284

RESUMO

PURPOSE: Following a diagnosis of breast cancer, BRCA mutation carriers face an increased risk of developing a second (contralateral) cancer in the unaffected breast. It is important to identify predictors of contralateral cancer in order to make informed decisions about bilateral mastectomy. The impact of bilateral salpingo-oophorectomy (i.e., oophorectomy) on the risk of developing contralateral breast cancer is unclear. Thus, we conducted a prospective study of the relationship between oophorectomy and the risk of contralateral breast cancer in 1781 BRCA1 and 503 BRCA2 mutation carriers with breast cancer. METHODS: Women were followed from the date of diagnosis of their first breast cancer until the date of diagnosis of a contralateral breast cancer, bilateral mastectomy, date of death, or date of last follow-up. Cox proportional hazards regression was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) of contralateral breast cancer associated with oophorectomy. Oophorectomy was included as a time-dependent covariate. We performed a left-censored analysis for those women who reported a primary breast cancer prior to study entry (i.e., from completion of baseline questionnaire). RESULTS: After an average of 9.8 years of follow-up, there were 179 (7.8%) contralateral breast cancers diagnosed. Oophorectomy was not associated with the risk of developing a second breast cancer (HR 0.92; 95% CI 0.68-1.25). The relationship did not vary by BRCA mutation type or by age at diagnosis of the first breast cancer. There was some evidence for a decreased risk of contralateral breast cancer among women with an ER-positive primary breast cancer, but this was based on a small number of events (n = 240). CONCLUSION: Overall, our findings suggest that oophorectomy has little impact on the risk of contralateral breast cancer.

7.
Transl Behav Med ; 2018 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-30418620

RESUMO

Risk-reducing mastectomy (RRM) and salpingo-oophorectomy (RRSO) are increasingly used to reduce breast and ovarian cancer risk following BRCA1/BRCA2 testing. However, little is known about how genetic counseling influences decisions about these surgeries. Although previous studies have examined intentions prior to counseling, few have examined RRM and RRSO intentions in the critical window between genetic counseling and test result disclosure. Previous research has indicated that intentions at this time point predict subsequent uptake of surgery, suggesting that much decision-making has taken place prior to result disclosure. This period may be a critical time to better understand the drivers of prophylactic surgery intentions. The aim of this study was to examine predictors of RRM and RRSO intentions. We hypothesized that variables from the Health Belief Model would predict intentions, and we also examined the role of affective factors. Participants were 187 women, age 21-75, who received genetic counseling for hereditary breast and ovarian cancer. We utilized multiple logistic regression to identify independent predictors of intentions. 49.2% and 61.3% of participants reported intentions for RRM and RRSO, respectively. Variables associated with RRM intentions include: newly diagnosed with breast cancer (OR = 3.63, 95% CI = 1.20-11.04), perceived breast cancer risk (OR = 1.46, 95% CI = 1.17-1.81), perceived pros (OR = 1.79, 95% CI = 1.38-2.32) and cons of RRM (OR = 0.81, 95% CI = 0.65-0.996), and decision conflict (OR = 0.80, 95% CI = 0.66-0.98). Variables associated with RRSO intentions include: proband status (OR = 0.28, 95% CI = 0.09-0.89), perceived pros (OR = 1.35, 95% CI = 1.11-1.63) and cons of RRSO (OR = 0.72, 95% CI = 0.59-0.89), and ambiguity aversion (OR = 0.79, 95% CI = 0.65-0.95). These data provide support for the role of genetic counseling in fostering informed decisions about risk management, and suggest that the role of uncertainty should be explored further.

8.
Int J Cancer ; 2018 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-30350351

RESUMO

The first two genome wide association studies (GWAS) of papillary thyroid carcinoma (PTC) detected five variants associated with PTC. Two of them (rs944289 and rs116909374) are located at 14q13 making that locus an important target of research into the genetic predisposition to PTC. We aimed at uncovering other variants at 14q13 associated with PTC independently from the GWAS variants. We performed next generation sequencing of the 14q13 region and analyzed the allele frequencies of single nucleotide polymorphisms (SNPs) in n = 90 PTC cases vs. n = 379 EUR controls from the 1,000 Genome Project. The variants associated with PTC were validated in an Ohio cohort of n = 1,216 PTC cases and n = 1,416 controls. Next, we analyzed the association between SNPs and expression of nearby genes and clinical parameters. We showed that rs368187 was associated with PTC (OR = 1.31, p = 2.20 × 10-6 ). Rs1632250, Rs1863347 and rs1755787 showed association with classical PTC (cPTC) (n = 891; OR = 1.24, 2.22 × 10-3 , OR = 1.31, p = 2.15 × 10-4 and OR = 1.24, p = 2.06 × 10-3 , respectively) while variant rs28397092 showed association with follicular variant (n = 243; OR = 1.51, p = 1.36 × 10-3 ). Rs1863347 was associated with suppression of PTCSC3 in unaffected thyroid tissue (p = 0.026). Rs1632250, rs1863347 and rs1755787 showed association with multifocality (OR = 1.85, p = 0.001, OR = 1.98, p = 0.001 and OR = 1.76, p = 0.003 respectively) and N stage (OR = 1.79, p = 0.014, OR = 1.73, p = 0.023 and OR = 1.81, p = 0.013, respectively) in microPTC (n = 328) while rs368187 was associated with M stage (OR = 0.56, p = 0.034) in cPTC. Our results disclose multiple variants associated with PTC and clinical features in the 14q13 superlocus. We suggest that translational genotype/phenotype studies should take into account not only somatic mutations but also germline variants.

9.
Horm Cancer ; 9(6): 433-439, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30088223

RESUMO

There are limited data on the role of neck ultrasound (US) in the surveillance of patients with follicular thyroid cancer (FTC). Here, we analyze the likelihood of US to find structural disease in patients with FTC and evaluate if initial American Thyroid Association (ATA) risk stratification and the response to therapy categories [the latter based on thyroglobulin (Tg) levels] modify that likelihood. We conducted a retrospective cohort study of 32 patients with FTC in our institution. We included all patients with well-differentiated FTC who underwent total thyroidectomy and radioactive iodine (RAI) treatment without neck structural disease at the time of RAI and with Tg and US at least 6 months after RAI. After a median follow-up of 4.3 years, two patients (6.3%) had structural disease by US. None of the 18 patients with initial ATA low-risk disease had structural disease by US in contrast to higher, but not significant, frequency of 18.2% (2/11) in patients with initial ATA high-risk disease (p = 0.14). Based on Tg levels, 24/32 patients had excellent response to therapy and 8/32 had biochemical incomplete/indeterminate response. None of the patients with excellent response had structural disease by US versus 2/8 (25%) patients with biochemical incomplete/indeterminate response all of whom had other sites of structural disease (p = 0.054). Our findings suggest that neck US in FTC is unlikely to find structural disease with initial low-risk ATA or excellent response to therapy but can detect structural disease in some patients with initial ATA high-risk or incomplete/indeterminate responses to therapy.

10.
J Clin Oncol ; 36(29): 2961-2968, 2018 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-30161022

RESUMO

PURPOSE: Lynch syndrome due to pathogenic variants in the DNA mismatch repair genes MLH1, MSH2, and MSH6 is predominantly associated with colorectal and endometrial cancer, although extracolonic cancers have been described within the Lynch tumor spectrum. However, the age-specific cumulative risk (penetrance) of these cancers is still poorly defined for PMS2-associated Lynch syndrome. Using a large data set from a worldwide collaboration, our aim was to determine accurate penetrance measures of cancers for carriers of heterozygous pathogenic PMS2 variants. METHODS: A modified segregation analysis was conducted that incorporated both genotyped and nongenotyped relatives, with conditioning for ascertainment to estimates corrected for bias. Hazard ratios (HRs) and corresponding 95% CIs were estimated for each cancer site for mutation carriers compared with the general population, followed by estimation of penetrance. RESULTS: In total, 284 families consisting of 4,878 first- and second-degree family members were included in the analysis. PMS2 mutation carriers were at increased risk for colorectal cancer (cumulative risk to age 80 years of 13% [95% CI, 7.9% to 22%] for males and 12% [95% CI, 6.7% to 21%] for females) and endometrial cancer (13% [95% CI, 7.0%-24%]), compared with the general population (6.6%, 4.7%, and 2.4%, respectively). There was no clear evidence of an increased risk of ovarian, gastric, hepatobiliary, bladder, renal, brain, breast, prostate, or small bowel cancer. CONCLUSION: Heterozygous PMS2 mutation carriers were at small increased risk for colorectal and endometrial cancer but not for any other Lynch syndrome-associated cancer. This finding justifies that PMS2-specific screening protocols could be restricted to colonoscopies. The role of risk-reducing hysterectomy and bilateral salpingo-oophorectomy for PMS2 mutation carriers needs further discussion.

11.
JAMA Oncol ; 4(8): 1059-1065, 2018 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-29710224

RESUMO

Importance: Prophylactic bilateral salpingo-oophorectomy is recommended for BRCA1 mutation carriers to prevent ovarian cancer. Whether or not hormone replacement therapy (HRT) initiated after oophorectomy is associated with an increased risk of breast cancer has not been evaluated in a prospective study. Objective: To determine the association between HRT use and BRCA1-associated breast cancer. Design, Setting, and Participants: A prospective, longitudinal cohort study of BRCA1 and BRCA2 mutation carriers from 80 participating centers in 17 countries was conducted between 1995 and 2017 with a mean follow-up of 7.6 years. Participants had sought genetic testing for a BRCA1 or BRCA2 mutation because of a personal or family history of breast and/or ovarian cancer. Carriers of BRCA1 mutation with no personal medical history of cancer who underwent bilateral oophorectomy following enrollment were eligible for the cohort study. Exposures: A follow-up questionnaire was administered every 2 years to obtain detailed information on HRT use. A left-truncated Cox proportional hazard analysis was used to estimate the hazard ratios (HRs) and 95% CIs associated with the initiation of HRT use postoophorectomy. Main Outcomes and Measures: Incident breast cancer. Results: A total of 872 BRCA1 mutation carriers with a mean postoophorectomy follow-up period of 7.6 years (range, 0.4-22.1) were included in this study. Mean (SD) age of participants was 43.4 (8.5) years. Among these, 92 (10.6%) incident breast cancers were diagnosed. Overall, HRT use after oophorectomy was not associated with an increased risk of breast cancer. The HR was 0.97 (95% CI, 0.62-1.52; P = .89) for ever use of any type of HRT vs no use; however, the effects of estrogen alone and combination hormonal therapy were different. After 10 years of follow-up, the cumulative incidence of breast cancer among women who used estrogen-alone HRT was 12% compared with 22% among women who used estrogen plus progesterone HRT (absolute difference, 10%; log rank P = .04). Conclusions and Relevance: These findings suggest that use of estrogen after oophorectomy does not increase the risk of breast cancer among women with a BRCA1 mutation and should reassure BRCA1 mutation carriers considering preventive surgery that HRT is safe. The possible adverse effect of progesterone-containing HRT warrants further study.

12.
Breast Cancer Res Treat ; 171(2): 421-426, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29774471

RESUMO

PURPOSE: In the general population, an early age at first full-term birth confers protection against the risk of developing breast cancer. The relationship between age at first birth and breast cancer risk is not clear for women with a mutation in the BRCA1 or BRCA2 gene. Thus, we undertook a case-control study of women with a BRCA1 or BRCA2 mutation to study the effects of age at first full-term birth matched for other reproductive factors. METHODS: Information about reproductive factors, including age at first birth as well as medical history, was collected from a routinely administered research questionnaire. There were 2,295 matched pairs of women with a BRCA1 or BRCA2 mutation included in the final analysis. RESULTS: There was no significant difference in the mean age at first full-term birth among the BRCA1 (24.9 vs. 25.2; P = 0.10) or BRCA2 mutation carriers (26.5 vs. 26.6 years; P = 0.80). Findings were similar in the analysis limited to cases who were diagnosed with breast cancer prior to age 45. CONCLUSION: This matched analysis of a large number of BRCA mutation carriers suggests that age at first birth has little influence on BRCA1 or BRCA2 breast cancer risk.

13.
Gynecol Oncol ; 150(1): 85-91, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29793803

RESUMO

OBJECTIVES: For women at high risk of developing ovarian cancer, it is important to provide an accurate recommendation for the optimal age for preventive surgery in order to maximize the preventative effect while delaying symptoms associated with early surgical menopause. The goal of the current study was to estimate age-specific incidence rates of ovarian cancer among women with a BRCA1 or BRCA2 mutation. METHODS: From our international registry, we identified 5689 women with no previous diagnosis of ovarian or fallopian tube cancer or preventive oophorectomy. Women were followed from the date of completion of the baseline questionnaire until either a diagnosis of ovarian or fallopian tube cancer, prophylactic oophorectomy, death or last follow-up. The annual and cumulative incidence rates of ovarian cancer were estimated. RESULTS: Over a mean follow-up period of 4.7 years (ranges 0-22.6), 195 incident ovarian or fallopian tube cancers were diagnosed (169 [86%] ovarian cancers, 22 [11%] fallopian tube cancers and four [2%] cancers that involved both the ovaries and fallopian tubes). Of these, 45 (23%) cancers were diagnosed at preventive surgery (occult cancers). The cumulative risk of ovarian cancer to age 80 was 49% for BRCA1 and 21% for BRCA2 mutation carriers. The mean age at diagnosis was 51.3 years (ranges 33-84) among women with a BRCA1 mutation and 61.4 years (ranges 44-80) among women with a BRCA2 mutation. CONCLUSION: Based on a cumulative risk of 0.55% to age 35 for BRCA1 mutation carriers and of 0.56% to age 45 for BRCA2 mutation carriers, we recommend bilateral salpingo-oophorectomy before age 40, but ideally by age 35, for women with a BRCA1 mutation and by age 45 for those with a BRCA2 mutation to maximize prevention and to minimize adverse effects.


Assuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Mutação , Neoplasias Ovarianas/genética , Adulto , Fatores Etários , Idoso , Proteína BRCA1/metabolismo , Proteína BRCA2/metabolismo , Feminino , Predisposição Genética para Doença , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Adulto Jovem
14.
J Genet Couns ; 27(5): 1291-1301, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29594659

RESUMO

Deciding between increased cancer screening or prophylactic surgery and the timing of such procedures can be a difficult and complex process for women with BRCA mutations. There are gaps in our understanding of involvement of others in the decision-making process for women with BRCA mutations. This study evaluated the management decision-making process of women with BRCA mutations, focusing on the involvement of others. Grounded theory was used to analyze and code risk management decision-making information from interviews with 20 BRCA mutation carriers. Unaffected at-risk participants with a BRCA mutation, those under age 40, and those with no children described having a difficult time making risk management decisions. Physicians were an integral part of the decision-making process by providing decisional support and management recommendations. Family members and other mutation carriers filled similar yet distinct roles by providing experiential information as well as decisional and emotional support for carriers. Participants described genetic counselors as short-term providers of risk information and management recommendations. The study findings suggest that unaffected at-risk women, women under 40, and those who do not have children may benefit from additional support and information during the decision-making process. Genetic counselors are well trained to help women through this process and connect them with resources, and may be under-utilized in long-term follow-up for women with a BRCA mutation.

15.
Int J Epidemiol ; 2018 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-29547931

RESUMO

Background: Although evidence suggests that larger body size in early life confers lifelong protection from developing breast cancer, few studies have investigated the relationship between body size and breast cancer risk among BRCA mutation carriers. Therefore, we conducted a prospective evaluation of body size and the risk of breast cancer among BRCA mutation carriers. Methods: Current height and body mass index (BMI) at age 18 were determined from baseline questionnaires. Current BMI and weight change since age 18 were calculated from updated biennial follow-up questionnaires. Cox proportional hazards models were used to estimate the hazard ratio (HR) and 95% confidence interval (CI). Results: Among 3734 BRCA mutation carriers, there were 338 incident breast cancers over a mean follow-up of 5.5 years. There was no association between height, current BMI or weight change and breast cancer risk. Women with BMI at age 18 ≥22.1 kg/m2 had a decreased risk of developing post-menopausal breast cancer compared with women with a BMI at age 18 between 18.8 and 20.3 kg/m2 (HR 0.49; 95% CI 0.30-0.82; P = 0.006). BMI at age 18 was not associated with risk of pre-menopausal breast cancer. Conclusions: There was no observed association between height, current BMI and weight change and risk of breast cancer. The inverse relationship between greater BMI at age 18 and post-menopausal breast cancer further supports a role of early rather than current or adulthood exposures for BRCA-associated breast cancer development. Future studies with longer follow-up and additional measures of adiposity are necessary to confirm these findings.

16.
J Genet Couns ; 27(4): 885-893, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29404823

RESUMO

Hereditary breast and ovarian cancer syndrome (HBOC) is a cancer predisposition syndrome that affects both men and women, with more significant cancer risk elevations in women. Dissemination patterns regarding familial genetic risk information among females with HBOC are fairly well defined, but knowledge about how males share this information is limited. We interviewed 21 people primarily Ashkenazi Jewish men who were accrued via listserv email through Facing Our Risk of Cancer Empowered (FORCE). Interviews focused on family cancer history, experiences with cancer and genetic testing, motivations to pursue genetic testing and subsequently disclose genetic test results, information-sharing patterns, health care provider response, and participants' emotional support systems. The interviews were transcribed in their entirety, coded, and analyzed based on recurring themes. Eighteen transcripts were used for the analysis. Results were classified into five main themes. Participants (n = 8) were most concerned about cancer risk for their children and female family members, and most (n = 11) mentioned that HBOC provides them increased personal awareness, but has a negligible impact on their life overall (n = 9). Men (n = 11) were interested in a male-focused support group to discuss HBOC and gain knowledge and information. Participants (n = 9) took on active and open communication roles with family members and health care providers. The majority of participants (n = 14) discussed the need for knowledge and awareness among the health care community and general population regarding male HBOC risks. This study serves as a pilot study and provides important and novel insights into psychosocial impacts, communication patterns, encounters with health care professionals, and expressed needs of males with HBOC.

17.
J Genet Couns ; 27(1): 9-15, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29075947

RESUMO

The Code of Ethics (COE) of the National Society of Genetic Counselors (NSGC) was adopted in 1992 and was later revised and adopted in 2006. In 2016, the NSGC Code of Ethics Review Task Force (COERTF) was convened to review the COE. The COERTF reviewed ethical codes written by other professional organizations and suggested changes that would better reflect the current and evolving nature of the genetic counseling profession. The COERTF received input from the society's legal counsel, Board of Directors, and members-at-large. A revised COE was proposed to the membership and approved and adopted in April 2017. The revisions and rationale for each are presented.

18.
Gynecol Oncol ; 147(1): 110-114, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28800943

RESUMO

OBJECTIVE: Analyze the impact of embedding genetic counseling services in gynecologic oncology on clinician referral and patient uptake of cancer genetics services. METHODS: Data were reviewed for a total of 737 newly diagnosed epithelial ovarian cancer patients seen in gynecologic oncology at a large academic medical center including 401 from 11/2011-7/2014 (a time when cancer genetics services were provided as an off-site consultation). These data were compared to data from 8/2014-9/2016 (n=336), when the model changed to the genetics embedded model (GEM), incorporating a cancer genetic counselor on-site in the gynecologic oncology clinic. RESULTS: A statistically significant difference in proportion of patients referred pre- and post-GEM was observed (21% vs. 44%, p<0.0001). Pre-GEM, only 38% of referred patients were actually scheduled for genetics consultation and post-GEM 82% were scheduled (p<0.00001). The difference in the time from referral to scheduling in genetics was also statistically significant (3.92months pre-GEM vs. 0.79months post-GEM, p<0.00001) as was the time from referral to completion of genetics consultation (2.52months pre-GEM vs. 1.67months post-GEM, p<0.01). Twenty-five percent of patients referred post GEM were seen by the genetic counselor on the same day as the referral. CONCLUSIONS: Providing cancer genetics services on-site in gynecologic oncology and modifying the process by which patients are referred and scheduled significantly increases referral to cancer genetics and timely completion of genetics consultation, improving compliance with guideline-based care. Practice changes are critical given the impact of genetic test results on treatment and familial cancer risks.


Assuntos
Aconselhamento Genético/organização & administração , Neoplasias dos Genitais Femininos/genética , Fidelidade a Diretrizes/normas , Serviço Hospitalar de Oncologia/organização & administração , Encaminhamento e Consulta/organização & administração , Adulto , Idoso , Prestação Integrada de Cuidados de Saúde/organização & administração , Feminino , Predisposição Genética para Doença , Neoplasias dos Genitais Femininos/terapia , Acesso aos Serviços de Saúde/organização & administração , Humanos , Pessoa de Meia-Idade , Modelos Organizacionais
19.
Ther Adv Med Oncol ; 9(8): 519-531, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28794804

RESUMO

Ovarian cancer is a heterogeneous disease that encompasses a number of different cellular subtypes, the most common of which is high-grade serous ovarian cancer (HGSOC). Still today, ovarian cancer is primarily treated with chemotherapy and surgery. Recent advances in the hereditary understanding of this disease have shown a significant role for the BRCA gene. While only a minority of patients with HGSOC will have a germline BRCA mutation, many others may have tumor genetic aberrations within BRCA or other homologous recombination proteins. Genetic screening for these BRCA mutations has allowed improved preventative measures and therapeutic development. This review focuses on the understanding of BRCA mutations and their relationship with ovarian cancer development, as well as future therapeutic targets.

20.
Nat Commun ; 8: 14517, 2017 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-28195142

RESUMO

The great majority of thyroid cancers are of the non-medullary type. Here we report findings from a genome-wide association study of non-medullary thyroid cancer, including in total 3,001 patients and 287,550 controls from five study groups of European descent. Our results yield five novel loci (all with Pcombined<3 × 10-8): 1q42.2 (rs12129938 in PCNXL2), 3q26.2 (rs6793295 a missense mutation in LRCC34 near TERC), 5q22.1 (rs73227498 between NREP and EPB41L4A), 10q24.33 (rs7902587 near OBFC1), and two independently associated variants at 15q22.33 (rs2289261 and rs56062135; both in SMAD3). We also confirm recently published association results from a Chinese study of a variant on 5p15.33 (rs2736100 near the TERT gene) and present a stronger association result for a moderately correlated variant (rs10069690; OR=1.20, P=3.2 × 10-7) based on our study of individuals of European ancestry. In combination, these results raise several opportunities for future studies of the pathogenesis of thyroid cancer.


Assuntos
Carcinoma Papilar/genética , Loci Gênicos , Estudo de Associação Genômica Ampla , Neoplasias da Glândula Tireoide/genética , Adulto , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , Cromossomos Humanos/genética , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Frequência do Gene/genética , Predisposição Genética para Doença , Variação Estrutural do Genoma , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Hormônios Hipofisários/análise , Fatores de Risco , Câncer Papilífero da Tireoide , Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/metabolismo , Sequenciamento Completo do Genoma
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