A Cohort Study of Hereditary Ovarian Cancer Risk Prediction Models and Pathogenesis Exploration
Conditions: Ovarian Neoplasms
Sponsor: Peking University Third Hospital

A Cohort Study of genetic ovarian cancer risk prediction models and
pathogenesis exploration
NCT06564428
2025-06-03

Program design
[ Design of the study methodology ]
The aim of this project is to establish a bidirectional multicenter cohort of hereditary
ovarian cancer and to describe the clinicopathologic features of hereditary ovarian
cancer patients in our country. The risk prediction model of ovarian cancer for
Chinese was established by following-up analysis of clinical and pathological
information, genetic test results and detailed family history, to predict the risk of
cancer in first-degree relatives of carriers of pathogenic/suspected pathogenic
mutations, and to guide the intervention management of high-risk population of
cancer.
The study will identify novel tumor-causing mutations/predisposing genes by gene
sequencing in a special family with hereditary tumor.
[ Eligibility, exclusion and withdrawal criteria ]
Topic 1: The clinicopathological features and gene mutation characteristics of
hereditary ovarian cancer
Case Group (hereditary ovarian cancer) inclusion criteria:
1) Epithelial ovarian cancer, age ≥18 years
2) The pathological diagnosis was clear, and the germ line pathogenic/suspected
pathogenic mutations were detected in the gene (the mutation interpretation was based
on ACMG genetic variation classification standard and guide)
Control Group (non-hereditary ovarian cancer) inclusion criteria:
1) Epithelial ovarian cancer, age ≥18 years
2) The pathological diagnosis was clear, and no germ line pathogenic or suspected
pathogenic mutation was detected by gene detection
Exclusion criteria:
1) Non-epithelial ovarian cancer was confirmed by pathology
2) No gene detection was performed

Topic 2: To construct a genetic ovarian cancer risk prediction model (to predict the
risk of ovarian cancer in first-degree relatives)
Case Group (hereditary ovarian cancer) inclusion criteria:
1) Female first-degree relatives of patients with hereditary ovarian cancer (Case
Group 1).
2) The first-degree relatives were tested for pathogenic or suspected pathogenic
mutation of germ line.
3) Ovarian cancer.
Control Group (non-hereditary ovarian cancer) inclusion criteria:
1) Female first-degree relatives of patients with hereditary ovarian cancer.
2) The first-degree relatives were tested for pathogenic or suspected pathogenic
mutation of germ line.
3) No ovarian cancer.
Exclusion criteria:
1) Female first-degree relatives did not undergo genetic testing.
Topic 3: To explore new tumor-causing mutations based on a special hereditary
ovarian cancer family
In subject 1, a few patients in control group had no known germline pathogenic or
suspected pathogenic mutation, however, it is suspected to be hereditary ovarian
cancer (≥3 patients with ovarian cancer/breast cancer in the family, 2 generations of
patients with the disease) based on the family history.
Case Group (hereditary ovarian cancer) inclusion criteria:
1) Ovarian cancer/breast cancer patients in a special hereditary ovarian cancer family.
2) The pathological diagnosis was clear, and the gene detection (whole exome
sequencing) did not detect the known pathogenic or suspected pathogenic mutation of
germ line.
The control group was included
1) The female patients with special hereditary ovarian cancer, whose age was ≥18
years old, did not have cancer.

2) No known germline pathogenic or suspected pathogenic mutation was detected by
gene detection (whole-exome sequencing).
Exclusion criteria:
1) No gene detection (whole-exome sequencing) was performed.
[ Study duration and follow-up ]
Topic 1:
Time
Content
After the
diagnosis
①personal history (age, BMI, oral contraceptive use, hormone
replacement therapy use, tubal ligation)
②menstrual marriage and childbearing history (whether or not
menopause, menopausal age, menarche age, the number of
births)
③personal history of tumor (history of malignant tumor, tumor
type, pathological type, tumor stage, age of onset)
④family history of cancer (family history of cancer or not,
number/person of cancer in first/second/third degree relatives,
relationship with patients, tumor type, pathological type, tumor
stage, age of onset, gene detection)
⑤results of gene detection (detection items, specimen type,
mutation, mutated gene, cDNA change, amino acid change,
mutation type, mutation significance)
Three years
after the
surgery
(Every 3-6
months)
Treatment,
physical
examination,
tumor
markers,
imaging
examination;
Genetic mutation, family history of cancer
After three
years
Treatment,
physical
examination,
tumor
markers,
imaging
examination;

(Every 6
months)
Genetic mutation, family history of cancer
Topic 2:
Time
Content
The same
time of the
gene test
①Personal history (age, BMI, oral contraceptive use, hormone
replacement therapy use, tubal ligation)
②Menstrual history of marriage and childbearing (whether
menopause, age of menopause, age of menstruation, number of
births)
③Personal history of tumor (whether there is a history of
malignant tumor, tumor type, pathological classification, tumor
stage, age of onset)
④Family history of cancer (whether there is a family history of
malignant
tumor,
the
number
of
first/second/third
degree
relatives suffering from malignant tumor, the relationship with
patients, tumor type, pathological classification, tumor stage, age
of onset, and genetic testing)
⑤Genetic test results (test items, specimen type, mutation or not,
mutant gene, cDNA change, amino acid change, mutation type,
mutation significance)
After the gene
test
(Every 6
months)
Have a tumor or not (if the subject have any, age and
pathological type);
Carry
germline
pathogenic/suspected
pathogenic
mutation,
family history of tumor.
Data management
1. Data Entry
Data collection will be obtained by team staff via the Case Report Form (CRF). As a

part of the clinical data management system, the case report form for data collection is
jointly negotiated and prepared by the project leader and the clinical epidemiology
Research Center, and the experts are invited to discuss and modify it for use. The data
collation process includes automated validation procedures and manual validation to
ensure the completeness and accuracy of the data entered into the case report form.
When the data does not match, the data can be queried, and the team staff can verify
and modify the entered data.
2. Contents and methods of data verification and management
According to the data entered in the case report form, medical supervision is
conducted regularly to ensure the accuracy of data entry, and medical problems are
discussed separately.
3. Data Archiving
After data entry and verification are completed as required, the case report form shall
be filed and stored in numbered order, and be filled with a retrieval catalogue for
reference. Electronic data files, including databases, inspection programs, analysis
programs, analysis results, coding and explanatory files, should be classified and
stored in different disks or recording media with multiple backups, properly stored to
prevent damage. All original files shall be kept for the period specified accordingly.

Statistical analysis
1. By
collecting
clinicopathological
characteristics
of
the
enrolled
subjects,
appropriate statistical methods such as univariate analysis, multi-factor analysis,
Chi-square test and survival analysis were selected for descriptive analysis.
2. Through follow-up analysis of clinical and pathological information, genetic test
results, detailed family history and other factors, a tumor risk prediction model was
established
to
predict
the
risk
of
cancer
in
first-degree
relatives
of
pathogenic/suspected pathogenic mutation carriers.
①The risk of hereditary tumor is preliminarily determined according to the family
map, and the risk of hereditary tumor in a family member is further calculated through
a mathematical model by combining individual clinicopathological information,
genetic test results and detailed family history. The statistical methods were Bayes
analysis, nomogram model, Logistic regression, cox regression, etc.
②Validation of the ovarian cancer risk prediction model: Expand the sample size of
the genetic ovarian cancer cohort, and evaluate the sensitivity, specificity, AUC curve,
positive predictive value and other indicators of the established model.

Informed consent
Protocol name: A Cohort Study of genetic ovarian cancer risk prediction models and
pathogenesis exploration
Setting: the Third Hospital of Peking University
Main researcher: Chief gynecologist Guo Hongyan
Patient name:
Initials:
Patient's address:
Patient's number:
We cordially invite you to participate in the“Cohort study of genetic ovarian cancer
risk prediction models and pathogenesis exploration”. Here are some questions you
may be interested in:
[Background]
The mortality rate of ovarian cancer is the highest in female genital malignant tumors.
About 75% of the patients were in the advanced stage at the time of diagnosis, and the
5-year survival rate was less than 30% . 10% -20% of ovarian cancers are related to
genetic factors.
The study of hereditary ovarian cancer is helpful to find out the susceptible population
of ovarian cancer, so as to intervene, prevent and diagnose ovarian cancer early.
Secondly, cancer susceptibility genes are closely related to targeted therapy, and the
study of Genetic predisposition is beneficial to the exploration and guidance of
individualized and precise therapy.
The special changes of genetic information in hereditary ovarian cancer patients make
them different from non-hereditary ovarian cancer patients in diagnosis, treatment and
prevention. Gene detection can not only make molecular pathological stratification of
ovarian cancer patients and identify the target of targeted therapy, but also provide
evidence for risk assessment and early prevention of the carrier's relatives, to make
the genetic risk assessment and clinical management of ovarian cancer more
individualized and accurate. However, there is a lack of large-scale cohort of
hereditary ovarian cancer in China, and data on genetic characteristics and pedigree
analysis are still scarce.

[ Objective ]
The aim of this project is to establish a prospective multicenter cohort of hereditary
ovarian cancer, based on which genetic ovarian cancer risk prediction models and
pathogenesis-related studies will be conducted. For the first time, this project will
establish an ovarian cancer risk prediction model suitable for Chinese people to guide
the prevention and intervention of high-risk population of tumor, to explore the new
pathogenesis of ovarian cancer, to guide the early diagnosis of hereditary ovarian
cancer, and to promote the individualized and accurate diagnosis and treatment of
hereditary ovarian cancer.
[Study design]
The aim of this project is to establish a bidirectional multi-center cohort of hereditary
ovarian cancer and to describe the clinical and pathological features of hereditary
ovarian cancer patients in our country. The risk prediction model of ovarian cancer for
Chinese was established by following-up analysis of clinical and pathological
information, genetic test results and detailed family history, to reduce the risk of
cancer in first-degree relatives of carriers of pathogenic/suspected pathogenic
mutations, and to guide the intervention management of high-risk population of
cancer.
The study will identify novel tumor-causing mutations/predisposing genes by gene
sequencing in a special family with hereditary tumor at the same time.
Topic 1: The clinicopathological features and gene mutation characteristics of
hereditary ovarian cancer
Case Group (hereditary ovarian cancer) inclusion criteria:
1) Epithelial ovarian cancer, age ≥18 years.
2) The pathological diagnosis was clear, and the germline pathogenic/suspected
pathogenic mutations were detected in the gene (the mutation interpretation was based
on ACMG genetic variation classification standard and guide).

Control Group (non-hereditary ovarian cancer) inclusion criteria:
1) Epithelial ovarian cancer, age ≥18 years.
2) The pathological diagnosis was clear, and no germline pathogenic or suspected
pathogenic mutation was detected by gene detection.
Exclusion criteria:
1) Non-epithelial ovarian cancer was confirmed by pathology.
2) No gene detection was performed.
Topic 2: To construct a genetic ovarian cancer risk prediction model (to predict the
risk of ovarian cancer in first-degree relatives)
Case Group (hereditary ovarian cancer) inclusion criteria:
1) Female first-degree relatives of patients with hereditary ovarian cancer (Case
Group 1).
2) The first-degree relatives were tested for pathogenic or suspected pathogenic
mutation of germ line.
3) Ovarian cancer.
Control Group (non-hereditary ovarian cancer) inclusion criteria:
1) Female first-degree relatives of patients with hereditary ovarian cancer.
2) The first-degree relatives were tested for pathogenic or suspected pathogenic
mutation of germ line.
3) No ovarian cancer.
Exclusion criteria:
2) Female first-degree relatives did not undergo genetic testing.
Topic 3: To explore new tumor-causing mutations based on a special hereditary
ovarian cancer family
In subject 1, a few patients in control group had no known germline pathogenic or
suspected pathogenic mutation, however, it is suspected to be hereditary ovarian
cancer (≥3 patients with ovarian cancer/breast cancer in the family, 2 generations of
patients with the disease) based on the family history.

Case Group (hereditary ovarian cancer) inclusion criteria:
1) Ovarian cancer/breast cancer patients in a special hereditary ovarian cancer family.
2) The pathological diagnosis was clear, and the gene detection (whole exome
sequencing) did not detect the known pathogenic or suspected pathogenic mutation of
germ line.
The control group was included
1) The female patients with special hereditary ovarian cancer, whose age was ≥18
years old, did not have cancer.
2) No known germline pathogenic or suspected pathogenic mutation was detected by
gene detection (whole-exome sequencing).
Exclusion criteria:
2) No gene detection (whole-exome sequencing) was performed.
[ Study test ]
Genetic testing
[ Study duration and follow-up ]
If you are involved in this study, you will need to receive multiple telephone or
outpatient follow-up visits.
Patients with ovarian cancer and mutation carriers will be followed up within 3 years
(every 3-6 months) and 3 years (every 6 months) after surgery.
If you participate in Project 2, you will be followed up at the time of the genetic test
and every 6 months after the genetic test.
The frequency of follow-up was 2 times per year for carriers of pathogenic/suspected
pathogenic mutations in the family.
The follow-up included detailed medical history and family history, pelvic
examination, blood routine and biochemical tests, serum CA125 level,
ultrasound/CT/MRI and other imaging examinations.
[ Risks ]

Due to technical limitations, the results of our genetic test are only for this sample and
only for scientific research. If you need further clinical decision-making, clinical
genetic testing can be performed again to guide decision-making.
[ If these drugs are used in the study, the study can not be continued ]
Blood samples and information are collected without the use of immune suppressive
drug and without the presence of any drug or alcohol abuse.
[ Expenses and compensation ]
This study will exempt you from the cost of genetic testing for family members other
than the proband.
[ Benefit ]
In this study, you can obtain the genetic test results of relevant family members, for
early screening and genetic block reference. And the results of this study can provide
great help for more hereditary ovarian cancer families.
[ Possible reasons for termination ]
Your participation in the trial is voluntary, you can refuse to participate or withdraw
from the trial in any way at any stage of the trial without discrimination or retaliation,
and your medical treatment and rights will not be affected. If your research physician
feels that it is not in your best interest to continue the study, he or she may decide to
withdraw you from the study. If this occurs, you will be notified and your research
physician will discuss the other options available to you.
[ New information ]
You will be informed of any new research findings and new treatments that arise in
the course of your research.
[ Privacy and confidentiality ]

During the study period, your name, gender and other personal data will be replaced
with code names or numbers, and be strictly confidential. Only the relevant doctors
know your data and your privacy will be well protected. The results may be published
in a journal, but will not reveal any of your personal information.
[ How to communicate with doctors and researchers during treatment ]
If you have any questions related to this study, please contact Dr. Li Yuan at
18610689868; If you need to know about the participants' rights during the study, you
can contact the Ethics Committee Office of Peking University Third Hospital at
(010)8226557182265176.
[ Notification Statement ]
“I have informed the subject of the background, objectives, steps, risks and benefits of
the study (cohort study of genetic ovarian cancer risk prediction models and
pathogenesis exploration) , given him/her sufficient time to read the informed consent,
discuss with others, and answer questions about the study; I have informed the subject
that he/she can contact (the researcher) at any time when he/she encounters problems
related to the study, and that he/she can contact the General Office of Scientific
Research Ethics of Peking University Third Hospital whenever he/she encounters
problems related to his/her rights/interests, and provided accurate contact details; I
have informed the subject that he/she can withdraw from the study at any time
without any reason; I have informed the subject that he/she will be given a copy of the
informed consent, which includes my signature and his/her signature.”
Signature of the researcher who obtain informed consent
___________________________
Contact telephone
__________________
Date
_________________

[ Statement of informed consent ]
I have been informed of the background, objectives, procedures, risks and benefits of
the study. I had enough time and opportunity to ask questions and I was satisfied with
the answers. I was also told who to contact when I had questions, grievances,
concerns, or wanted further information. I have read this informed consent form,
agreed to participate in this study, and promised to provide researchers with
information, laboratory test results are true and effective. I know that I can withdraw
from this study at any time without any reason. I was told that I would receive a copy
of this informed consent form, which included my signature and that of the
researcher.
Signature of the subject
___________________________
Contact telephone
__________________
Date
_________________