Korean patients with hereditary cancer: a prospective multicentre cohort study protocol exploring psychosocial and health outcomes

Abstract

Introduction

Although genetic testing for hereditary cancers is increasing, data on health attitudes based on genetic pathogenicity are limited. This cohort study aims to establish three subcohorts based on genetic testing results to assess the health impact of genetic variations. This study evaluates changes in participant quality of life (QoL), unmet needs and mental health over time based on their genetic variant status.

Methods and analysis

This prospective cohort study will recruit 1435 patients with suspected hereditary cancer who have undergone BRCA1/2 or next-generation sequencing (NGS) testing. The study began in July 2023 and will continue until December 2027. By 2026, participants will be surveyed up to four times annually during their outpatient visits. The survey consists of 342 items across 5 domains: comorbidities (96), health behaviours (80), QoL (41), unmet needs (75) and mental health (50). Data were collected using 11 validated surveys. In addition, information on the chronic diseases, cancer diagnoses, medical history and treatment history of participants will be extracted from their electronic medical records to analyse their health status and cancer treatment experiences. Genetic variant data from BRCA1/2 and NGS will be used to classify participants into three subcohorts: pathogenic variants, variants of uncertain significance and undetectable mutations. A three-generation pedigree that includes details such as the year of cancer diagnosis, age at diagnosis, cancer type, survival status of family members and age at death will be constructed for each participant. The collected data will be linked to secondary sources such as cancer registries and National Health Insurance Service data to provide a comprehensive analysis of the impact of hereditary cancer on health and survival.

Ethics and dissemination

The study protocol was approved by all the Ethics Committees: the National Cancer Center IRB (NCC2023-0179), the Samsung Medical Center IRB (SMC2023-09-057), the Yonsei University Health System, Severance Hospital IRB (4-2023-0627), the Hanyang University Guri Hospital IRB (GURI2023-08-021) and the Keimyung University IRB (DSMC IRB 2024-05-048). The study outcomes will be disseminated through conference presentations, peer-reviewed publications and social media.

Trial registration number

KCT0009460.

Correspondence to Dr Sun-Young Kong; [email protected]

Strengths and limitations of this study

• The Korean hereditary cancer cohort study is a large-scale multicentre study conducted at five major university hospitals in Korea, targeting 1435 patients.

• The study is designed to track participants through annual surveys over 5 years, analysing long-term health outcomes, changes in quality of life and unmet healthcare needs based on genetic variant status. This will help understand the evolving healthcare needs of patients with hereditary cancer.

• Participants are classified into three subcohorts based on pathogenic variants, variants of uncertain significance and undetectable variants (no detectable), allowing for a precise analysis of differences in health outcomes according to genetic status.

• The participating hospitals are concentrated in metropolitan areas, the study does not include patients from rural regions, which may limit the external validity of the results.

• There may be challenges in achieving statistical significance when analysing smaller subgroups with rarer genetic mutations or specific conditions.

Introduction

The diagnosis of hereditary cancers has steadily increased, primarily owing to the introduction of BRCA1/2 genetic testing and advancements in next-generation sequencing (NGS)^1–3 (figure 1). Hereditary cancers account for 5%–10% of all cancer cases and are mostly inherited in an autosomal-dominant manner.⁴ This often results in the sharing of identical genetic variants among family members, which significantly affects familial health management.

Figure 1. Trends in hereditary cancer diagnostic testing in Korea from 2017 to 2022. The data for this figure were sourced from the Health Insurance Review and Assessment Service Big Data Open Portal. It illustrates the increase in the number of next-generation sequencing-based genetic panel tests conducted annually to diagnose hereditary diseases in Korea.

Hereditary cancers generally occur at a younger age and pose a higher cancer risk compared with sporadic cancers. Individuals with pathogenic variants (PVs) in the BRCA1 and BRCA2 genes have a 65%–80% and 45%–85% risk of developing breast cancer, respectively, and a 37%–62% and 11%–23% risk of developing ovarian cancer, respectively.⁵ However, the genetic variants that cause hereditary cancer are often unidentifiable during genetic testing on individuals suspected of hereditary cancer. Variants of uncertain significance (VUS) are detected in many cases. A VUS is defined as a genetic variant for which the association with the disease has not been clearly established. Current scientific knowledge and available data cannot classify these variants as pathogenic or benign. Additionally, no known mutations or variants have been identified in some cases.^{6 7}

Uncertainty and confusion regarding various genetic test results and their management can lead to severe psychological stress in patients with hereditary cancer, including anxiety, depression and fear of cancer recurrence.⁸ In addition, sharing genetic information with family members can cause tensions and conflicts within families. Moreover, the lack of genetic counselling makes it difficult for individuals to make informed decisions regarding health management and preventive measures.⁹ Living with the risk of hereditary cancer has long-term effects, including continuous health surveillance, lifestyle adjustments and the possibility of preventive surgeries, which substantially affect the overall quality of life (QoL) in patients and family members who share genetic components.¹⁰ In addition, clinical management becomes ambiguous when a personal or family history of hereditary cancer is suspected but an uncertain variant is detected.¹¹ Given the limited research on uncertain variants, it is necessary to conduct additional data analyses on these variants.¹² To enhance clinical studies targeting hereditary cancer, it is essential to prioritise patients with detailed family histories, including pedigrees and to incorporate a broad range of pathogenic genetic variants.¹³ Establishing cohorts that include patients with VUS or inconclusive test results can provide valuable control groups and aid in the consistent interpretation of genetic findings.¹⁴

Existing research on patients with hereditary cancer has primarily focused on white women, neglecting the diverse racial and cultural contexts of patients worldwide.^15–17 Studies involving Asian populations are relatively rare, and large-scale investigations targeting Koreans are almost non-existent.^{18 19} Consequently, there is a critical lack of systematic data on the QoL, mental health and medical needs of Korean patients with hereditary cancer. This study aims to bridge this gap by establishing a multi-institutional cohort of patients with hereditary cancer in Korea to analyse long-term changes in health status, QoL and mental health.

Despite the rapid increase in hereditary cancer, the exact number of hereditary cancers is small. Thus, it is essential to establish a multi-institutional cohort to collect substantial data and systematically study the health problems of patients with hereditary cancer and those who are suspected to have hereditary cancer without established causative variants. Previous studies have highlighted the unmet needs of healthcare providers concerning hereditary cancers, including the lack of clinical guidelines, need for reduced testing costs and necessity for additional testing for undiagnosed hereditary cancers.²⁰ The provision of tailored healthcare may address unmet healthcare needs, improve health outcomes and enhance QoL. Therefore, the present study aimed to identify long-term health impacts of genetic variations. This study further aimed to evaluate changes in QoL, unmet needs and mental health according to genetic variant status to promote health improvement and QoL. This approach will also support the development and validation of personalised healthcare technologies.

Methods and analysis

Study aim

In this study, we established a prospective cohort of Korean patients with hereditary cancer (table 1). Three subcohorts will be formed based on the genetic test variant results: patients with PV, VUS and no detectable mutations (ND).

Table 1

Project research question and hypotheses

Questions	Hypotheses
How do the long-term health impacts differ among patients with hereditary cancer characterised by pathogenic variants (PV), variants of uncertain significance (VUS) and undetected (ND) variants?	Patients with PV will experience higher cancer incidence rates and more health complications over the long term than those with VUS and ND variants.
What is the relationship between genetic variant status and changes in quality of life among patients with hereditary cancer over time?	Patients with PV will experience greater stress and anxiety than those with VUS and ND variants, leading to a more considerable decline in quality of life scores over time.
How do unmet healthcare needs and mental health outcomes differ based on genetic variant status in patients with hereditary cancer?	Patients with PV will require more healthcare services and psychological support and will have higher rates of mental health issues, such as anxiety and depression, than those with VUS and ND variants.

Study design

This study is a prospective multicentre cohort study conducted in five hospitals: National Cancer Center, Samsung Medical Center, Severance Hospital, Hanyang University Guri Hospital and Keimyung University Dongsan Hospital. The research protocols are as follows (figure 2):

• Participant registration: Researchers at each participating institution explained the study objective, research procedures and methods, potential risks and discomfort associated with participation, and the right of patients suspected of having hereditary cancer to voluntarily withdraw from the study at any time. Informed consent was obtained from the participants for study participation and the use of human biological materials. Relevant data, including family history, clinical data, genetic test results and blood samples, are collected after enrolling the participants. Blood samples stored in the Department of Laboratory Medicine were collected as specified in the informed consent form. Specifically, residual blood samples of at least 4 mL in EDTA bottles were collected. Next, plasma and buffy coat were separated and stored at −80°C. These residual blood samples were used to identify the risk factors and prognostic predictors of hereditary cancer.

• Survey: The survey is conducted over a 5-year period, with four annual follow-up surveys after the baseline. The survey consists of 342 items across 5 domains: comorbidities, health behaviours, QoL, unmet needs and mental health.

• Expected cohort output: The data collected in this study will provide foundational information for clinical and genetic research on hereditary cancers in Korea. These data will help establish clinical guidelines for patients with hereditary cancer, propose policies for patient management and support and promote clinical advancements through detailed and practical clinical research on hereditary cancer.

• Short-term outcome: The short-term goals of this study are to evaluate changes in QoL, identify unmet needs and assess mental health and health behaviours. QoL encompasses the overall patient well-being, including physical, mental and social health. Unmet needs refer to the demands of patients not currently met by existing healthcare services. Survey tools validated for patients with cancer are used to evaluate how the QoL of the participants changes. Baseline QoL scores and changes will be analysed at each follow-up.

  Additionally, the study annually tracks changes in participant mental health by evaluating depression, suicidal thoughts, anxiety, fear of cancer recurrence and disease awareness using standardised survey tools. It also analyses how knowledge of genetic status affects lifestyle choices and preventive health measures through the annual monitoring of health behaviours. Unmet needs are assessed using comprehensive survey tools designed to capture general and hereditary cancer-specific requirements, helping identify the most common unmet needs among patients.

• Long-term outcome: The long-term objectives of this study are as follows: (1) To track cancer incidence and analyse causes of death. This will involve the monitoring of new cancer cases and systematic analysis of the causes of death through annual follow-ups, including medical records, self-reports and official death records; (2) We use secondary data linkages to track cancer incidence and analyse the causes of death. This involves using the system of data integration established by authorised institutions to protect personal information and link secondary data sources, such as the cancer registry and National Health Insurance (NHI) Service data. This approach aims to obtain more accurate and comprehensive data on cancer incidence and causes of death.

Figure 2. Establishing a protocol logic for the hereditary cancer cohort. QoL-CS, Quality of Life-Cancer Survivor; PHQ-9, Patient Health Questionnaire-9; CNAT, Comprehensive Needs Assessment Tool in cancer; MINI, Mini International Neuropsychiatric Interview; GAD-7, Generalised Anxiety Disorder-7; BIPQ, Brief Illness Perception Questionnaire; EORTC-QLQ-C30, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30; EQ-5D-5L, EuroQol 5-Dimension 5-Level.

Inclusion criteria

The high risk of cancer among patients with suspected hereditary cancer is attributed to genetic factors, such as family history, age at cancer onset and the occurrence of specific cancer types in multiple family members.^{21 22}

According to the 2012 NHI coverage guidelines in Korea, BRCA1/2 PV testing is recommended for patients with breast cancer and ovarian cancer who meet the following criteria: a family history of breast or ovarian cancer within second-degree relatives, early-onset breast cancer (diagnosed at age ≤40 years), bilateral breast cancer, concurrent breast and ovarian cancer, male breast cancer or multiple primary cancers. The NHI coverage guidelines revised in 2020 further recommended BRCA1/2 PV testing for patients with breast cancer with a family history of the disease, ovarian cancer, male breast cancer, metastatic prostate cancer or pancreatic cancer within third-degree relatives; early-onset breast cancer (diagnosed at age ≤40 years); triple-negative breast cancer diagnosed at age ≤60 years; bilateral breast cancer; concurrent breast cancer with ovarian or pancreatic cancer; male breast cancer or epithelial ovarian cancer (including fallopian tube and primary peritoneal cancer), excluding histologically pure mucinous ovarian cancer. Additionally, NGS has been conditionally covered with 50% co-payment since March 2017, and the co-payment rate increased to 80% in December 2023.

This study included patients suspected of hereditary cancer who underwent genetic counselling and related genetic testing, regardless of insurance coverage status. Based on the results of genetic testing, patients were categorised into three groups: PV (PV or likely PV), VUS and not detected (likely benign or benign).

According to the American College of Medical Genetics and Genomics (ACMG) guidelines, genetic variants are classified into five categories: pathogenic, likely pathogenic, uncertain significance, likely benign and benign.²³ However, this study categorised patients into three groups—PV, VUS and ND—to systematically evaluate the clinical and psychological indicators of patients with hereditary cancer. This classification established a group of patients with clinically significant variants closely associated with the disease, while also including groups of patients with VUS and those with no detected variants as comparative cohorts. These groups served as valuable control cohorts for future clinical research. By doing so, the study aimed to provide a detailed evaluation of the clinical and psychological characteristics of each group and to better understand the impact of genetic testing results on the health and QoL of patients with hereditary cancer.

Study population estimate

The extent to which patient-centred decision-making is implemented in clinical settings in South Korea remains largely understudied. Consequently, evidence on this topic often relies on international literature. A study conducted at a tertiary university hospital in South Korea reported that 37.4% of orthopaedic patients engaged in patient-centred decision-making. Additionally, a national survey of the general population indicated that 33.5%–44.3% of individuals prefer shared decision-making between patients and healthcare providers.²⁴

In this study, we hypothesised that the rate of patient-centred decision-making without intervention would be approximately 30%. We further assumed that using a tailored decision-making tool would increase this rate by 10%, increasing it to a total of 40%. A two-proportion test with a significance level (α) of 5% and a power (1–β) of 85% was performed based on these assumptions. The required sample size was calculated to be 405 patients in each group. When the power was set to 80%, the required sample size was 354 patients per group, resulting in a total of 708 patients.

Considering an estimated drop-out rate of 20% and the fact that the number of patients with PV was expected to be lower than that of those with VUS or negative variants, the target sample size was adjusted. The final target sample size was set at 1435 patients to ensure equal enrollment of patients with PV and those with VUS or negative variants. Sample size estimation was conducted to establish a cohort of Korean patients with hereditary cancer.

Data collection items

This study collected clinical, survey, genetic variant and pedigree data from the participants.

• Clinical data: Clinical data were directly extracted by researchers with access to electronic medical records. These data included histories of chronic diseases (eg, hypertension, diabetes and heart disease), cancer diagnosis (year of diagnosis, age at diagnosis, and type and stage of cancer), and surgeries related to cancer treatment (date of surgery, type and outcome). Treatment history included the current and past types, duration, and outcomes of anticancer therapies (chemotherapy, radiotherapy and hormone therapy), including related side effects and complications. The test results include health assessment outcomes, such as general blood tests, cancer marker tests, ECGs and pulmonary function tests. Imaging data include the results and interpretations of imaging tests conducted during cancer diagnosis and treatment, such as Computed Tomography (CT), Magnetic Resonance Imaging (MRI), Positron Emission Tomography (PET) and ultrasonography. Anthropometric data include patient weight, height, body mass index and other measurements. Obstetric, menstrual, breastfeeding and hormone use histories are also included for female patients.

• Surveys: The surveys were designed to be completed within 20 min to facilitate ease of response for the participants and were structured to be administered as interviewer-administered questionnaires. The survey tools were tailored to different time points: at the time of cancer diagnosis; during treatment (typically four months postdiagnosis); and at 1, 2, 3 and 4 years intervals postdiagnosis. These surveys collect detailed information on lifestyle factors, environmental exposures and other health-related data.

• Genetic variants: Genetic mutation data were obtained using BRCA1/2 or NGS panel testing (online supplemental table S1). Based on these results, patients were classified into three subcohorts: PV, VUS and ND.

• Family history and pedigree: Pedigree data were collected by the participants after they were educated on how to construct a pedigree chart encompassing three generations. This includes information on the years of cancer diagnosis, age at diagnosis and type of cancer among family members, as well as whether the family member is deceased and their age at death. This structured approach ensures comprehensive data collection and analysis suitable for the research objectives.

• Biospecimen collection: Biological samples are collected from the blood of participants in accordance with protocols outlined in the informed consent documentation, with storage facilitated by the Department of Laboratory Medicine. Specifically, we use residual blood samples collected following clinical blood collection. A minimum of 4 mL of residual blood is collected in EDTA tubes. Postcollection, the plasma and buffy coat are separated and stored in an ultra-low temperature freezer at −80°C. These residual blood samples will be used to identify risk factors and prognostic predictors associated with hereditary cancer. This approach is integral for improving the accuracy of assessing genetic risk factors and clinical prognoses related to hereditary cancer.

Survey tools and data collection

Data were collected as follows: Baseline surveys are initially conducted with participants following receipt of their genetic test results. Subsequently, annual follow-up surveys will be conducted for 4 years from the baseline survey data. Surveys were self-administered through questionnaires or telephone interviews. Participants were provided with explanations by well-trained nurses who assisted them in completing the questionnaires or in conducting telephone surveys to record their responses.

In this study, data were collected from participants using 11 different survey tools (table 2).

Table 2

An overview of survey questionnaire

Area	N of items	Subarea	Survey tool
Comorbidities	96	–	Korea National Health and Nutrition Examination Survey
Health behaviour	80	Obesity and weight management
		Alcohol consumption
		Mental health
		Smoking/secondhand smoke/smoking cessation
		Oral health
		Physical activity
		Sleep health
		Dietary habits
Quality of life	41	Quality of life in patients with cancer	EORTC-QLQ-C30
		General quality of life	EQ-5D-5L
Unmet needs	75	Comprehensive needs assessment	CNAT
		Hereditary cancer-specific needs assessment	Development of additional items
Mental health	50	Depression	PHQ-9
		Suicide	MINI
		Anxiety	GAD-7
		Fear of cancer recurrence	QOL-CS
		Disease awareness	BIPQ

BIPQ, Brief Illness Perception Questionnaire; CNAT, Comprehensive Needs Assessment Tool in cancer; EORTC-QLQ-C30, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30; EQ-5D-5L, EuroQol 5-Dimension 5-Level; GAD-7, Generalised Anxiety Disorder-7; MINI, Mini International Neuropsychiatric Interview; PHQ-9, Patient Health Questionnaire-9; Qol-CS, Quality of Life-Cancer Survivor.

• Comorbidities: The current medical diagnostic status of the study participants was recorded using the Korea National Health and Nutrition Examination Survey.²⁵ Major chronic conditions included hypertension, diabetes and cardiovascular diseases. In addition, the presence of malignant tumours such as gastric cancer, liver cancer, colorectal cancer and other conditions was noted. Detailed information on comorbidities, including age at diagnosis and current treatment status, was collected to comprehensively assess the health status of participants and to analyse the occurrence and treatment status of comorbidities.

• Health behaviours: The Korea National Health and Nutrition Examination Survey consists of eight detailed items for evaluating health-related behaviours.^{25 26} (1) Obesity and weight management were assessed using self-reported weight changes and weight management methods over the previous year. (2) Alcohol consumption was evaluated by measuring the frequency and quantity of alcohol consumption to assess the health risk factors related to alcohol consumption. (3) General mental health status was assessed using standardised questions. (4) Smoking status, passive smoking exposure, as well as cessation attempts and intention were evaluated to assess smoking-related health risks. (5) Oral health status was assessed through self-reporting of dental hygiene habits and oral health problems. (6) Physical activity was assessed by measuring the frequency, duration and intensity of physical activity. (7) Sleep health was assessed by evaluating sleep duration, quality and disturbances to identify sleep-related issues. (8) Finally, dietary habits were evaluated by assessing the frequency and diversity of food intake. A comprehensive evaluation of individual health habits and lifestyles was conducted through responses to each item used as foundational data for health promotion.

• QoL: The general and cancer-specific QoL was assessed using the EuroQol 5-Dimension 5-Level (EQ-5D-5L) questionnaire to measure five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety or depression.²⁷ Each dimension was evaluated on a 5-point scale and scored from 1 (no problem) to 5 (severe problem). The responses were subsequently combined to express a five-digit number representing health status. This facilitated a comprehensive assessment of general QoL levels. The QoL of patients with cancer was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC-QLQ-C30), which consists of functional (physical, role, emotional, cognitive and social functioning), symptom (fatigue, nausea, vomiting, pain, dyspnoea, insomnia, loss of appetite, constipation, diarrhoea and financial difficulties), an overall health status and single-item scales.²⁸ Each item was evaluated on a Likert scale ranging from 1 (not at all) to 4 (very much), with higher scores indicating better functional status and worse symptom burden.

• Unmet needs: This assessment comprised comprehensive and hereditary cancer-specific needs. Comprehensive needs were assessed using the Comprehensive Needs Assessment Tool in cancer (CNAT) to evaluate the following subdomains: information and education, psychological issues, medical staff, physical symptoms, hospital facilities and services, family/interpersonal issues, religious/spiritual issues, and social support.²⁹ Each item was rated from 0 (not at all needed) to 3 (extremely needed). Specific needs related to hereditary cancer were assessed using the Study for HeredItary questionnaire Development questionnaire developed by the research team, with a focus on information and education, psychological issues, medical services and social support.³⁰ Each item was rated on a scale of 0 (not at all needed) to 3 (extremely needed). Scores for each item were calculated to determine the level of need, with higher scores indicating a greater need.

• Mental health: This evaluation comprises five detailed areas: depression, suicide risk, anxiety, fear of cancer recurrence and illness perception. The depression domain was assessed using the Patient Health Questionnaire-9 (PHQ-9) to evaluate nine depressive symptoms, with each item scored from 0 (not at all) to 3 (nearly every day). This yielded a total score of 0–27, with higher scores indicating higher levels of depression.³¹ Furthermore, suicide risk was assessed using the Mini International Neuropsychiatric Interview (MINI) questionnaire to evaluate the suicide risk levels of respondents based on their thoughts, plans and attempts. Each item was scored as yes (1 point) or no (0 points).³² The anxiety domain was assessed using the Generalized Anxiety Disorder-7 (GAD-7) questionnaire to evaluate seven anxiety symptoms. Each item was scored from 0 (not at all) to 3 (nearly every day), yielding a total score of 0–21; higher scores indicate higher anxiety levels.³³ Moreover, fear of cancer recurrence was assessed using the Quality of Life-Cancer Survivor (QOL-CS) questionnaire to measure the concerns of cancer survivors about recurrence from various aspects. Each item was scored from 0 (not at all) to 3 (very much), with higher scores indicating greater fear of cancer recurrence.³⁴ Illness perception was assessed using the Brief Illness Perception Questionnaire (BIPQ) to measure the perceptions and attitudes of patients towards the disease. The BIPQ consists of nine items that are each scored on a scale of 0–10, with higher scores indicating stronger negative perceptions of the disease.³⁵ The scores for each item are summed to calculate the overall illness perception score, with higher scores indicating stronger negative perceptions of the disease.

Study plan

The study commenced in July 2023. Following participant enrolment and discussions among the research team, 11 survey instruments were used to comprehensively collect baseline data in the first year. Subsequent follow-up surveys are scheduled annually, with the scope and items to be determined based on an analysis of the first year’s results.

Data management

The data were collected by well-trained nurses who directly interacted with the participants to administer the survey. The nurses provided detailed explanations of the survey questions and content to ensure that the participants responded completely and accurately. Each participant was assigned a unique research identification number to anonymise the data. These identifiers were used to enter data into a deidentified database, thereby protecting personal information and maintaining privacy.

The collected data were reviewed and validated monthly. To enhance the accuracy and completeness, an automated system was employed to identify and correct out-of-range values, missing fields and input errors, ensuring the integrity of the data. Monthly meetings were held with all researchers to discuss issues arising during data collection and seek solutions, facilitating protocol adherence and continuous improvement.

Access to the database was strictly controlled; the analytical database was encrypted and restricted to essential members of the research team. These procedures were established to maintain high standards of data integrity, privacy and security while promoting continual protocol compliance and improvement through regular oversight and discussions.

Data linkage

This study initially collected baseline data through annual surveys over the first 4 years. From the fifth year onwards, we will conduct a long-term follow-up study by linking secondary data sources, including the cancer registry, National Health Insurance Service (NHIS) and mortality data from Statistics Korea. This approach will facilitate a systematic analysis of cancer incidence, secondary cancers, the onset of other diseases and causes of mortality among participants.

Pseudonymised data were used to ensure the protection of personal information. Data linkage will be performed securely and reliably through a pseudonym information integration system provided by the NHIS, Health Insurance Review and Assessment Service and Korea Health Industry Development Institute.

The linked data will be used for various analyses, including the tracking of cancer incidence, analysis of mortality causes, examination of secondary cancer occurrences and investigation of comorbid chronic diseases.

Patient and public involvement

Our study aims to integrate the needs of patients with hereditary cancer into the research process and effectively disseminate research findings to them. By collaborating with patient representatives, we seek to actively incorporate the perspectives of both patients and the general public, ensuring that the study is designed and conducted in alignment with their real-world needs and interests.

In this study, we will collect survey data on the health behaviours, QoL, unmet medical needs and mental health of patients with hereditary cancer. Based on this data and feedback from patient representatives, we aim to identify additional research questions that reflect patient experiences and perspectives. This approach will help ensure that the study addresses the actual needs of patients and generates meaningful and practical results. We plan to invite groups of patients with hereditary cancer to share the study findings and evaluate how they interpret and perceive the results. This process will allow us to refine the findings and present them in a way that is easily understandable to a broader audience.

We will further collaborate with patient representatives to develop strategies for effectively disseminating research output, ensuring that the plain language summary is clear and accessible to all.

Ethics and dissemination

The study protocol has been approved by the Ethics Committees of the participating institutions: the National Cancer Center Institutional Review Board (IRB) (NCC2023-0179), the Samsung Medical Center IRB (SMC2023-09-057), the Yonsei University Health System, Severance Hospital IRB (4-2023-0627), the Hanyang University Guri Hospital IRB (GURI2023-08-021) and the Keimyung University IRB (DSMC IRB 2024-05-048). Each IRB is responsible for overseeing all aspects of the study to ensure compliance with ethical standards. All participants who agree to take part in the study will sign an informed consent form. The study protocol has been registered with the Clinical Research Information Service in Korea under the registration number KCT0009460, and the study results will be presented at both national and international conferences. The research data will be linked with related institutions and deposited at the National Cancer Data Center. Personal identifiable information will be encrypted and stored separately from other research data.

Discussion

Most studies on hereditary cancer have been conducted in Western populations, with only small-scale studies focusing on Korean populations.³⁶ Previous multiethnic Asian cohort studies involving 1056 patients with suspected hereditary breast cancer have provided insight into the prevalence of genetic variants across various Asian ethnicities, including Chinese, Malay, Indian and Middle Eastern populations.³⁷ These studies highlighted the genetic diversity and risk variations among these groups and demonstrated the feasibility and effectiveness of guideline-based panel testing in Asians with suspected hereditary breast cancer. BRCA1/2 and multigene panel tests have been covered by health insurance since 2018 in Japan.³⁸ However, there remains a need for medical staff and patient education to improve access to genetic testing and counseling. Risk-reducing mastectomy and bilateral salpingo-oophorectomy are performed at rates of 19.3% and 24.1%, respectively in Japan, with many institutions considering their introduction. These studies emphasise the specific needs for and genetic diversity in the management of hereditary cancers across various Asian populations. Furthermore, they demonstrate the need for tailored genetic testing panels, comprehensive risk assessments, and development of region-specific guidelines for effective management and prevention strategies.

Research on Korean populations is insufficient compared to Western studies, and Korea lacks integrated management of patients with hereditary cancer.³⁹ Some variability has been observed in the risk assessment for secondary cancers, preventive surgeries and screening recommendations across medical institutions. Additionally, there is a need for comprehensive studies on genetic testing and management of families.

Korean guidelines for BRCA mutation carriers include screening recommendations for breast and ovarian cancers in women and breast and prostate cancers in men.⁴⁰ Additionally, screening principles for other cancers, such as pancreatic, gastric and colorectal cancers, have been proposed. However, there is a lack of clear evidence regarding the appropriate timing and methods for screening these cancers, limiting their practical application. In contrast, the guidelines in the USA and the UK provide more detailed and systematic strategies for managing hereditary cancers. The NCCN guidelines in the USA emphasise regular monitoring and early detection of various cancers, including breast, ovarian, pancreatic cancers and melanoma, with specific and detailed recommendations tailored to each cancer type.⁴¹ Similarly, the NICE guidelines in the UK adopt a broader approach, encompassing high-risk individuals with BRCA1/2 or TP53 mutations. These guidelines provide tailored surveillance strategies and recommendations for preventive surgeries based on family history and individual risk factors (online supplemental table S2).⁴²

Our study aims to establish a cohort of patients with hereditary cancer in Korea by collecting substantial data to address the unmet healthcare needs of these patients. This will enable tailored medical interventions and support services that consider the genetic, environmental and cultural characteristics of the Korean population.

This study has some limitations. First, the participating hospitals are concentrated in metropolitan areas. This limits the collection of data from patients with hereditary cancer who reside in rural areas. This restriction reduces the external validity of the study and increases the risk of overlooking important information related to the characteristics of hereditary cancers in patients residing in rural areas. Second, the accuracy of the survey data has limitations. Respondents may not accurately report their health status or may rely on memory when answering questions about comorbidities or family histories, leading to a recall bias that can undermine the reliability of the study results. Therefore, it is essential to use objective data sources, such as electronic medical records, and to collect data through multiple verification processes to enhance data reliability.

This study aims to elucidate the practical issues and challenges faced by Koreans during the diagnosis and treatment of hereditary cancer. We formed three cohorts: patients with PV, VUS and negative variants. We aim to identify the specific needs of each variant group and propose a comprehensive care plan. This approach will support genetic counseling and testing accessibility, communication with healthcare providers, psychological support and decision-making regarding treatment and preventive measures.

Our study will contribute to a better understanding of the genetic and environmental factors involved in hereditary cancers. The collection of survey data from participants will provide insights into their health behaviours, QoL and unmet needs and elucidate differences among the cohorts. We will also collect genomic data and biospecimens to secure samples for future research and develop a variant risk assessment model using PV prediction. This will further reveal the factors influencing the onset and progression of hereditary cancers and facilitate the development of personalised treatment and prevention strategies.

Finally, establishing a cohort of Korean patients with hereditary cancer will lead to further research in the field of hereditary cancer in Korea. This will consequently address the specific medical needs of this population. Moreover, our findings will highlight the importance of equitable healthcare access and support for the development of medical and health policies aimed at ensuring a healthy life for all individuals.

We would like to extend our sincere gratitude to all the participants for their invaluable contributions to this study. We thank the National Cancer Center, Samsung Medical Center, Hanyang University College of Medicine, Yonsei University College of Medicine and Keimyung University Dongsan Hospital for their unwavering support and collaboration throughout this study. We would like to extend special thanks to the clinical research coordinators and clinicians who were instrumental in the data collection and patient follow-up processes. We also acknowledge the contributions of the Cancer Big Data Center of the National Cancer Center and the survey administrators for their meticulous efforts in ensuring the accuracy and integrity of the collected data.

Ethics statements

Patient consent for publication

Not applicable.

Footnote

X @77192ncc

BP and S-YK contributed equally.

Contributors J-KK drafted the manuscript. M-AJ, JEP, DW, J-SH, K-BK, BP and S-YK contributed to the study design and conception, as well as the overall study planning. J-KK, BP and S-YK critically revised the manuscript and prepared the final version. All authors contributed to the revision of the manuscript and approved the final version for submission. S-YK is responsible for the overall content as guarantor. We partly used ChatGPT4 to translate from Korean to English.

Funding This work was supported by the Korean Cancer Survivors Healthcare R&D Project through the National Cancer Center, which is funded by the Ministry of Health and Welfare, Republic of Korea (Grant numbers RS-2023-CC13920 (NCC-23F1850)).

Competing interests None declared.

Patient and public involvement Patients and/or the public were involved in the design, or conduct, or reporting, or dissemination plans of this research. Refer to the Methods section for further details.

Provenance and peer review Not commissioned; externally peer reviewed.

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