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Kari Hemminki - One of the best experts on this subject based on the ideXlab platform.
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concordant and discordant Familial Cancer Familial risks proportions and population impact
International Journal of Cancer, 2017Co-Authors: Christoph Frank, Jan Sundquist, Akseli Hemminki, Kari HemminkiAbstract:Relatives of Cancer patients are at an increased risk of the same (concordant) Cancer but whether they are at a risk for different (discordant) Cancers is largely unknown - beyond well characterized hereditary Cancer syndromes - but would be of major scientific and clinical interest. We therefore decided to resolve the issue by analyzing Familial risks when family members were diagnosed with any discordant Cancers. We compared the population impact of concordant to discordant Familial Cancer. The Swedish Family-Cancer Database (FCD) was used to calculate Familial relative risks (RRs) for family members of Cancer patients, for the 27 most common Cancers. Population attributable fractions (PAFs) were estimated for concordant and discordant family histories. Discordant Cancers in the family were detected as significant risk factors for the majority of Cancers, although the corresponding RRs were modest compared to RRs for concordant Cancers. Risks increased with the number of affected family members with the highest RRs for pancreatic (2.31), lung (1.69), kidney (1.98), nervous system (1.79) and thyroid Cancers (3.28), when 5 or more family members were diagnosed with discordant Cancers. For most Cancers, the PAF for discordant family history exceeded that for concordant family history. Our findings suggest that there is an unspecific genetic predisposition to Cancer with clinical consequences. We consider it unlikely that shared environmental risk factors could essentially contribute to the risks for diverse discordant Cancers, which are likely driven by genetic predisposition. The identification of genes that moderately increase the risk for many Cancers will be a challenge.
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population landscape of Familial Cancer
Scientific Reports, 2015Co-Authors: Christoph Frank, Mahdi Fallah, Jan Sundquist, Akseli Hemminki, Kari HemminkiAbstract:Public perception and anxiety of Familial Cancer have increased demands for clinical counseling, which may be well equipped for gene testing but less prepared for counseling of the large domain of Familial Cancer with unknown genetic background. The aim of the present study was to highlight the full scope of Familial Cancer and the variable levels of risk that need to be considered. Data on the 25 most common Cancers were obtained from the Swedish Family Cancer Database and a Poisson regression model was applied to estimate relative risks (RR) distinguishing between family histories of single or multiple affected first-degree relatives and their diagnostic ages. For all Cancers, individual risks were significantly increased if a parent or a sibling had a concordant Cancer. While the RRs were around 2.00 for most Cancers, risks were up to 10-fold increased for some Cancers. Familial risks were even higher when multiple relatives were affected. Although Familial risks were highest at ages below 60 years, most Familial cases were diagnosed at older ages. The results emphasized the value of a detailed family history as a readily available tool for individualized counseling and its preventive potential for a large domain of non-syndromatic Familial Cancers.
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the population impact of Familial Cancer a major cause of Cancer
International Journal of Cancer, 2014Co-Authors: Christoph Frank, Mahdi Fallah, Jan Sundquist, Kari HemminkiAbstract:The population attributable fraction (PAF) defines the proportion of a disease that would be prevented if the exposure to a particular risk factor was avoided. Familial risk is a known risk factor for many Cancers, but an unbiased estimation of the PAF for Familial risk requires a large study population to include rare Cancers. PAFs and their corresponding standardized incidence ratios (SIRs) were calculated for Familial relative risk among first-degree relatives (FDRs) and second-degree relatives (SDRs) diagnosed with the same (concordant) invasive or in situ Cancers. Calculations were based on the Swedish Family-Cancer Database considering 8,148,737 individuals. To assess environmental effects, PAFs were also calculated for concordant Cancers among spouses. Almost all Cancers showed a significant Familial risk. The highest PAFs were found for the common Cancers of the prostate (13.94%), breast (7.46%) and colorectum (6.78%) among the FDRs. In the FDRs, the overall PAF for any concordant Cancer was 4.20%, but in the SDRs, it was only 0.34%. The overall PAFs for in situ Cancers were 0.86% and 0.56% for the FDRs and SDRs, respectively. The overall independent Familial PAF was 5.96% for the invasive and in situ Cancers in the FDRs and SDRs. The Cancers between spouses yielded an overall PAF of 0.14%. For esophageal Cancer, the risk among spouses was higher than the Familial risk. Our study shows that the overall Familial PAF of 5.96%, although underestimated for sex-specific Cancers, ranks as the third most common population burden after tobacco smoking and unhealthy diet.
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effect of multiplicity laterality and age at onset of breast Cancer on Familial risk of breast Cancer a nationwide prospective cohort study
Breast Cancer Research and Treatment, 2014Co-Authors: Elham Kharazmi, Kari Hemminki, Tianhui Chen, Steven A Narod, Kristina SundquistAbstract:The objective of this nationwide prospective cohort study is to find out the risk of breast Cancer (BC) in relatives of patients with multiple BCs by laterality and age at diagnosis of first BC. Having family history of single (HR 1.8; 95 % CI 1.8–1.9) or multiple (HR 2.7; 95 % CI 2.6–2.9) BC was associated with higher risk of BC. Those with an FDR with contralateral BC at any age had the highest risk of Familial Cancer except at age 60) having a FDR with contralateral BC at an advanced age (≥80). Despite the common belief that later onset breast Cancer is more associated with sporadic breast Cancer, our data suggest that breast Cancer at any age in the family is associated with some increase in the Familial risk, though that risk decreases as the age of onset increases. Contralateral and multiple ipsilateral breast Cancers might be associated with distinct shared Familial risk factors. Our results have implication for genetic counseling and urge gene identification studies.
Bettina Meiser - One of the best experts on this subject based on the ideXlab platform.
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psychosocial and behavioral impact of breast Cancer risk assessed by testing for common risk variants protocol of a prospective study
BMC Cancer, 2017Co-Authors: Tatiane Yanes, Gillian Mitchell, Maryanne Young, Bettina Meiser, Jane Halliday, Rajneesh Kaur, Kristine Barlowstewart, Tony Roscioli, Paul A JamesAbstract:The ‘common variant, common disease’ model predicts that a significant component of hereditary breast Cancer unexplained by pathogenic variants in moderate or high-penetrance genes is due to the cumulative effect of common risk variants in DNA (polygenic risk). Assessing a woman’s breast Cancer risk by testing for common risk variants can provide useful information for women who would otherwise receive uninformative results by traditional monogenic testing. Despite increasing support for the utility of common risk variants in hereditary breast Cancer, research findings have not yet been integrated into clinical practice. Translational research is therefore critical to ensure results are effectively communicated, and that women do not experience undue adverse psychological outcomes. In this prospective study, 400 women with a personal and/or high risk family history of breast Cancer will be recruited from six Familial Cancer centers (FCCs) in Australia. Eligible women will be invited to attend a FCC and receive their personal polygenic risk result for breast Cancer. Genetic health professionals participating in the study will receive training on the return of polygenic risk information and a training manual and visual aids will be developed to facilitate patient communication. Participants will complete up to three self-administered questionnaires over a 12-months period to assess the short-and long-term psychological and behavioral outcomes of receiving or not receiving their personal polygenic risk result. This is the world’s first study to assess the psychological and behavioral impact of offering polygenic risk information to women from families at high risk of breast Cancer. Findings from this research will provide the basis for the development of a new service model to provide polygenic risk information in Familial Cancer clinics. The study was retrospectively registered on 27th April 2017 with the Australian and New Zealand Clinical Trials Group (Registration no: ACTRN12617000594325; clinical trial URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372743 ).
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the impact of predictive genetic testing for hereditary nonpolyposis colorectal Cancer three years after testing
Genetics in Medicine, 2007Co-Authors: Veronica Collins, Bettina Meiser, Obioha C Ukoumunne, Clara Gaff, James D B St John, Jane HallidayAbstract:Background: To fully assess predictive genetic testing programs, it is important to assess outcomes over periods of time longer than the 1-year follow-up reported in the literature. Methods: We conducted a 3-year study of individuals who received predictive genetic test results for previously identified Familial mutations in Australian Familial Cancer Clinics. Questionnaires were sent before attendance at the Familial Cancer clinic and 2 weeks, 4 months, 1 year, and 3 years after receiving test results. Psychological measures were included each time, and preventive behaviors were assessed at baseline and 1 and 3 years. Psychological measures were adjusted for age, gender, and baseline score. Results: The study included 19 carriers and 54 non-carriers. We previously reported an increase in mean Cancer-specific distress in carriers at 2 weeks with a return to baseline levels by 12 months. This level was maintained until 3 years. Non-carriers showed sustained decreases after testing with a significantly lower level at 3 years compared with baseline (P < 0.001). These scores tended to be lower than those for carriers at 3 years (P = 0.09). Mean depression and anxiety scores did not differ between carriers and non-carriers and, at 3 years, were similar to baseline. All carriers and 7% of non-carriers had had a colonoscopy by 3 years, and 69% of 13 female carriers had undergone gynecological screening in the previous 2 years. Prophylactic surgery was rare. Conclusion: This report of long-term data indicates appropriate screening and improved psychological measures for non-carriers with no evidence of undue psychological distress in carriers of hereditary nonpolyposis colorectal Cancer mutations.
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psychological impact of genetic testing for Cancer susceptibility an update of the literature
Psycho-oncology, 2005Co-Authors: Bettina MeiserAbstract:This article presents an overview of the rapidly evolving body of literature on the psychological impact of genetic testing for hereditary breast/ovarian Cancer susceptibility, hereditary non-polyposis colorectal Cancer (HNPCC) and Familial adenomatous polyposis (FAP). Uptake of genetic testing for BRCA1/2 and HNPCC-related mutations is more consistently related to psychological factors, rather than sociodemographic variables. Most studies on the psychological impact of genetic testing amongst individuals who have never been affected by Cancer demonstrate that non-carriers derive significant psychological benefits from genetic testing, while no adverse effects have been observed amongst carriers. These benefits are more clear-cut for HNPCC, compared to hereditary breast/ovarian Cancer, reflecting differences in risk management options. The few studies available on individuals affected with Cancer indicate that the impact of genetic testing is mediated and amplified by their former experience of Cancer. Future directions and challenges of research in this area are reviewed. In particular, more empirical data are needed on the broader impact of genetic testing on those with inconclusive results or results of uncertain significance. As genetic testing is becoming available for other types of Familial Cancer, additional investigations will be needed as there is evidence to suggest that the impact of genetic testing may be unique to each type of Familial Cancer. Copyright © 2005 John Wiley & Sons, Ltd.
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psychological impact of genetic testing for hereditary non polyposis colorectal Cancer
Clinical Genetics, 2004Co-Authors: Bettina Meiser, Veronica Collins, Clara Gaff, Jane Halliday, R Warren, Djb St John, Ma Young, K Harrop, Judith E BrownAbstract:: The psychological impact of predictive genetic testing for hereditary non-polyposis colorectal Cancer (HNPCC) was assessed in 114 individuals (32 carriers and 82 non-carriers) attending Familial Cancer clinics, using mailed self-administered questionnaires prior to, 2 weeks, 4 months and 12 months after carrier status disclosure. Compared to baseline, carriers showed a significant increase in mean scores for intrusive and avoidant thoughts about colorectal Cancer 2 weeks (t = 2.49; p = 0.014) and a significant decrease in mean depression scores 2 weeks post-notification of result (t = -3.98; p < 0.001) and 4 months post-notification of result (t = -3.22; p = 0.002). For non-carriers, significant decreases in mean scores for intrusive and avoidant thoughts about colorectal Cancer were observed at all follow-up assessment time points relative to baseline. Non-carriers also showed significant decreases from baseline in mean depression scores 2 weeks, 4 months and 12 months post-notification. Significant decreases from baseline for mean state anxiety scores were also observed for non-carriers 2 weeks post-notification (t = -3.99; p < 0.001). These data indicate that predictive genetic testing for HNPCC leads to psychological benefits amongst non-carriers, and no adverse psychological outcomes were observed amongst carriers.
Jane Halliday - One of the best experts on this subject based on the ideXlab platform.
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psychosocial and behavioral impact of breast Cancer risk assessed by testing for common risk variants protocol of a prospective study
BMC Cancer, 2017Co-Authors: Tatiane Yanes, Gillian Mitchell, Maryanne Young, Bettina Meiser, Jane Halliday, Rajneesh Kaur, Kristine Barlowstewart, Tony Roscioli, Paul A JamesAbstract:The ‘common variant, common disease’ model predicts that a significant component of hereditary breast Cancer unexplained by pathogenic variants in moderate or high-penetrance genes is due to the cumulative effect of common risk variants in DNA (polygenic risk). Assessing a woman’s breast Cancer risk by testing for common risk variants can provide useful information for women who would otherwise receive uninformative results by traditional monogenic testing. Despite increasing support for the utility of common risk variants in hereditary breast Cancer, research findings have not yet been integrated into clinical practice. Translational research is therefore critical to ensure results are effectively communicated, and that women do not experience undue adverse psychological outcomes. In this prospective study, 400 women with a personal and/or high risk family history of breast Cancer will be recruited from six Familial Cancer centers (FCCs) in Australia. Eligible women will be invited to attend a FCC and receive their personal polygenic risk result for breast Cancer. Genetic health professionals participating in the study will receive training on the return of polygenic risk information and a training manual and visual aids will be developed to facilitate patient communication. Participants will complete up to three self-administered questionnaires over a 12-months period to assess the short-and long-term psychological and behavioral outcomes of receiving or not receiving their personal polygenic risk result. This is the world’s first study to assess the psychological and behavioral impact of offering polygenic risk information to women from families at high risk of breast Cancer. Findings from this research will provide the basis for the development of a new service model to provide polygenic risk information in Familial Cancer clinics. The study was retrospectively registered on 27th April 2017 with the Australian and New Zealand Clinical Trials Group (Registration no: ACTRN12617000594325; clinical trial URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372743 ).
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the impact of predictive genetic testing for hereditary nonpolyposis colorectal Cancer three years after testing
Genetics in Medicine, 2007Co-Authors: Veronica Collins, Bettina Meiser, Obioha C Ukoumunne, Clara Gaff, James D B St John, Jane HallidayAbstract:Background: To fully assess predictive genetic testing programs, it is important to assess outcomes over periods of time longer than the 1-year follow-up reported in the literature. Methods: We conducted a 3-year study of individuals who received predictive genetic test results for previously identified Familial mutations in Australian Familial Cancer Clinics. Questionnaires were sent before attendance at the Familial Cancer clinic and 2 weeks, 4 months, 1 year, and 3 years after receiving test results. Psychological measures were included each time, and preventive behaviors were assessed at baseline and 1 and 3 years. Psychological measures were adjusted for age, gender, and baseline score. Results: The study included 19 carriers and 54 non-carriers. We previously reported an increase in mean Cancer-specific distress in carriers at 2 weeks with a return to baseline levels by 12 months. This level was maintained until 3 years. Non-carriers showed sustained decreases after testing with a significantly lower level at 3 years compared with baseline (P < 0.001). These scores tended to be lower than those for carriers at 3 years (P = 0.09). Mean depression and anxiety scores did not differ between carriers and non-carriers and, at 3 years, were similar to baseline. All carriers and 7% of non-carriers had had a colonoscopy by 3 years, and 69% of 13 female carriers had undergone gynecological screening in the previous 2 years. Prophylactic surgery was rare. Conclusion: This report of long-term data indicates appropriate screening and improved psychological measures for non-carriers with no evidence of undue psychological distress in carriers of hereditary nonpolyposis colorectal Cancer mutations.
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psychological impact of genetic testing for hereditary non polyposis colorectal Cancer
Clinical Genetics, 2004Co-Authors: Bettina Meiser, Veronica Collins, Clara Gaff, Jane Halliday, R Warren, Djb St John, Ma Young, K Harrop, Judith E BrownAbstract:: The psychological impact of predictive genetic testing for hereditary non-polyposis colorectal Cancer (HNPCC) was assessed in 114 individuals (32 carriers and 82 non-carriers) attending Familial Cancer clinics, using mailed self-administered questionnaires prior to, 2 weeks, 4 months and 12 months after carrier status disclosure. Compared to baseline, carriers showed a significant increase in mean scores for intrusive and avoidant thoughts about colorectal Cancer 2 weeks (t = 2.49; p = 0.014) and a significant decrease in mean depression scores 2 weeks post-notification of result (t = -3.98; p < 0.001) and 4 months post-notification of result (t = -3.22; p = 0.002). For non-carriers, significant decreases in mean scores for intrusive and avoidant thoughts about colorectal Cancer were observed at all follow-up assessment time points relative to baseline. Non-carriers also showed significant decreases from baseline in mean depression scores 2 weeks, 4 months and 12 months post-notification. Significant decreases from baseline for mean state anxiety scores were also observed for non-carriers 2 weeks post-notification (t = -3.99; p < 0.001). These data indicate that predictive genetic testing for HNPCC leads to psychological benefits amongst non-carriers, and no adverse psychological outcomes were observed amongst carriers.
Jan Sundquist - One of the best experts on this subject based on the ideXlab platform.
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concordant and discordant Familial Cancer Familial risks proportions and population impact
International Journal of Cancer, 2017Co-Authors: Christoph Frank, Jan Sundquist, Akseli Hemminki, Kari HemminkiAbstract:Relatives of Cancer patients are at an increased risk of the same (concordant) Cancer but whether they are at a risk for different (discordant) Cancers is largely unknown - beyond well characterized hereditary Cancer syndromes - but would be of major scientific and clinical interest. We therefore decided to resolve the issue by analyzing Familial risks when family members were diagnosed with any discordant Cancers. We compared the population impact of concordant to discordant Familial Cancer. The Swedish Family-Cancer Database (FCD) was used to calculate Familial relative risks (RRs) for family members of Cancer patients, for the 27 most common Cancers. Population attributable fractions (PAFs) were estimated for concordant and discordant family histories. Discordant Cancers in the family were detected as significant risk factors for the majority of Cancers, although the corresponding RRs were modest compared to RRs for concordant Cancers. Risks increased with the number of affected family members with the highest RRs for pancreatic (2.31), lung (1.69), kidney (1.98), nervous system (1.79) and thyroid Cancers (3.28), when 5 or more family members were diagnosed with discordant Cancers. For most Cancers, the PAF for discordant family history exceeded that for concordant family history. Our findings suggest that there is an unspecific genetic predisposition to Cancer with clinical consequences. We consider it unlikely that shared environmental risk factors could essentially contribute to the risks for diverse discordant Cancers, which are likely driven by genetic predisposition. The identification of genes that moderately increase the risk for many Cancers will be a challenge.
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population landscape of Familial Cancer
Scientific Reports, 2015Co-Authors: Christoph Frank, Mahdi Fallah, Jan Sundquist, Akseli Hemminki, Kari HemminkiAbstract:Public perception and anxiety of Familial Cancer have increased demands for clinical counseling, which may be well equipped for gene testing but less prepared for counseling of the large domain of Familial Cancer with unknown genetic background. The aim of the present study was to highlight the full scope of Familial Cancer and the variable levels of risk that need to be considered. Data on the 25 most common Cancers were obtained from the Swedish Family Cancer Database and a Poisson regression model was applied to estimate relative risks (RR) distinguishing between family histories of single or multiple affected first-degree relatives and their diagnostic ages. For all Cancers, individual risks were significantly increased if a parent or a sibling had a concordant Cancer. While the RRs were around 2.00 for most Cancers, risks were up to 10-fold increased for some Cancers. Familial risks were even higher when multiple relatives were affected. Although Familial risks were highest at ages below 60 years, most Familial cases were diagnosed at older ages. The results emphasized the value of a detailed family history as a readily available tool for individualized counseling and its preventive potential for a large domain of non-syndromatic Familial Cancers.
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the population impact of Familial Cancer a major cause of Cancer
International Journal of Cancer, 2014Co-Authors: Christoph Frank, Mahdi Fallah, Jan Sundquist, Kari HemminkiAbstract:The population attributable fraction (PAF) defines the proportion of a disease that would be prevented if the exposure to a particular risk factor was avoided. Familial risk is a known risk factor for many Cancers, but an unbiased estimation of the PAF for Familial risk requires a large study population to include rare Cancers. PAFs and their corresponding standardized incidence ratios (SIRs) were calculated for Familial relative risk among first-degree relatives (FDRs) and second-degree relatives (SDRs) diagnosed with the same (concordant) invasive or in situ Cancers. Calculations were based on the Swedish Family-Cancer Database considering 8,148,737 individuals. To assess environmental effects, PAFs were also calculated for concordant Cancers among spouses. Almost all Cancers showed a significant Familial risk. The highest PAFs were found for the common Cancers of the prostate (13.94%), breast (7.46%) and colorectum (6.78%) among the FDRs. In the FDRs, the overall PAF for any concordant Cancer was 4.20%, but in the SDRs, it was only 0.34%. The overall PAFs for in situ Cancers were 0.86% and 0.56% for the FDRs and SDRs, respectively. The overall independent Familial PAF was 5.96% for the invasive and in situ Cancers in the FDRs and SDRs. The Cancers between spouses yielded an overall PAF of 0.14%. For esophageal Cancer, the risk among spouses was higher than the Familial risk. Our study shows that the overall Familial PAF of 5.96%, although underestimated for sex-specific Cancers, ranks as the third most common population burden after tobacco smoking and unhealthy diet.
Ingrid Winship - One of the best experts on this subject based on the ideXlab platform.
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prevalence of palb2 mutations in australasian multiple case breast Cancer families
Breast Cancer Research, 2013Co-Authors: Zhi Ling Teo, Ingrid Winship, Daniel J Park, Elena Provenzano, Catherine A Chatfield, Fabrice Odefrey, Tu Nguyendumont, James G Dowty, John L HopperAbstract:Introduction Population-based studies of breast Cancer have estimated that some PALB2 mutations confer a breast Cancer risk (penetrance) comparable to the average pathogenic mutation in BRCA2. As this risk is of clinical relevance, we sought to identify mono-allelic PALB2 mutations and determine their frequencies in multiple-case breast Cancer families attending Familial Cancer Clinics in Australia and New Zealand.
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cultural enhancement of a clinical service to meet the needs of indigenous people genetic service development in response to issues for new zealand maori
Clinical Genetics, 2007Co-Authors: R V Port, Nick Gravish, Julie Arnold, D. Kerr, Ingrid WinshipAbstract:The delivery of good health care services within clinical settings is predicated by an understanding of the needs of the stakeholders*. Most of the information generated to date on the transfer of mutational analysis to clinical service has been within a Eurocentric model favouring individual autonomy. It is predictable that this model does not easily translate for other cultures. Current genetic technology has elucidated the molecular basis of many diseases. In Familial Cancer and other late-onset disorders, there is now the possibility of ‘prediction’ where a high risk conferred by family history can be confirmed or negated by genetic testing. In paediatric disorders, prediction is offered in the form of prenatal or pre-implantation genetic diagnosis. We report on the processes undertaken in an attempt to provide a culturally sensitive service for the Maori people of Aotearoa, New Zealand.