Chinese National Human Genome Center at Shanghai

The Shanghai Human Genome Research Center was established in March 1998, and was designated as the Chinese National Human Genome Center at Shanghai (CHGC) on October 29.

Scientific Objectives: To align with the scientific frontier of international genomics research and to meet the major needs of China's biomedical development, to participate in international competition and cooperation in human genome sequencing and gene identification, and to further conduct China-specific medical genomics research.

Development Strategies: To establish a technical platform to allow structural and functional genomic research, to improve the overall level of genomic research in China through joint mechanisms, and to contribute to the establishment and industrialization of China's biomedical innovation system.

Based on multi-omics research and combined with the concepts of systems biology, utilizing artificial intelligence as well as big data technology, CHGC is committed to providing first-class molecular biology technology services, clinical molecular diagnostic test products, and health management services.

As of October 18, 2021, whole BRCA1/2 exome screening has been performed on 269,290 individuals, to build the largest database and biobank of BRCA1/2 germline mutations among a healthy population in the world.

High-end chips, leading genetic technology

A low-cost, high-throughput, high-quality BRCA whole exome screening program was established, which has had a highly positive impact on the early diagnosis, screening, and precise treatment of breast and ovarian cancers.

CHGC has specialized in genetic testing services for over 20 years

5-10% of tumors are caused by genetic variations

Hereditary tumors are defined as tumors caused by germline pathogenic mutations in relative genes and aggregated within families.

·Approximately 5-10% of cancers stemmed from genetic variations

·and have a 50% chance of passing on the risk of cancer to the next generation

·BRCA1, a tumor suppressor gene, is involved in the regulation of a variety of cellular processes, including transcription, protein ubiquitination, cell cycle regulation, and homologous recombination DNA damage repair. Germline mutations of the BRCA1 gene may lead to hereditary breast and ovarian cancer  syndrome (HBOC), an autosomal dominant disorder that increases the risk of breast and ovarian cancer. In addition, germline mutations of the BRCA1 gene may also lead to an increased risk of prostate and pancreatic cancers.

·BRCA2, a tumor suppressor gene, is involved in the transcription, cell cycle regulation, and homologous recombination DNA damage repair processes. Germline mutations of the BRCA2 gene may cause HBOC syndrome, an autosomal dominant disorder that increases the risk of breast and ovarian cancer. Further, germline mutations of the BRCA2 gene significantly increase the risk of prostate cancer, pancreatic cancer, and other malignancies.

4-fold increased risk of recurrence of contralateral breast cancer in patients with BRCA gene mutations, at 10 years after initial breast cancer diagnosis

Significance of BRCA genetic testing in healthy populations

The significance of active health management has been demonstrated by a manner in which accurate knowledge of genetic risk via BRCA genetic testing has allowed precise prevention before disease onset.

lPARP inhibitors are the first cancer drugs targeting germline mutations, and BRCA gene mutations are the preferred PARP inhibitor-sensitive biomarkers.
lFour PARP inhibitors have been approved for marketing in China, and seven others are being tested in clinical trials.
lAs many as 10 indicators have been approved or are being investigated, and there will be drugs available for more cancer types in the future.

Significance of BRCA genetic testing in patients

Stage I: Research findings(11,000 cases)

BMJ (2018): Prevalence of BRCA1/BRCA2 pathogenic variations in a Han Chinese population
 

Stage 2: September 2018 - August 2021

From September 2018 to August 2021, a total of 238,627 iKang Group customers have undergone BRCA genetic testing, of which 1,295 customers were found to have pathogenic variants of the BRCA gene, with an incidence of 0.54%. In other words, there is 1 BRCA pathogenic variant carrier per 185 Han Chinese individuals, meaning there are approximately 7.03 million BRCA pathogenic variant carriers among approximately 1.3 billion Han Chinese individuals.
 

Among the 182,566 people who had received both BRCA genetic testing and mammography, 975 cases with BRCA pathogenic variants were detected, of which 341 cases had mammography results showing breast nodules, with a detection rate of 34.97%, which was higher than the overall average detection rate of 25.68% for breast nodules in iKang.
 

The tumor marker glycoprotein 15-3 (CA15-3) is also one of the common indicators used to screen for breast cancer, and blood CA15-3 levels are significantly elevated during breast cancer. Analysis has shown that 13,821 individuals undergoing routine health examinations in Chengdu area who received BRCA genetic testing also received glycoantigen 15-3 testing. The detection rate of elevated glycoantigen 15-3 was 3.95% (3/76) in carriers of BRCA pathogenic variantsand 0.96% (132/13,745) in non-caarriers.
 

（As of 18 October 2021: 269,290 cases）

Does the test need to be performed every year?

No, this BRCA test is a germline genetic test and only needs to be performed once in a lifetime.

If the result is negative, does that mean I won't get the disease?

No, a negative result only means you have no risk of developing the disease because of mutations in the BRCA gene.

If the result is positive, does that mean I have a disease?

No, it is simply a genetic mutation and present health status requires diagnosis by a medical professional.

I already have the disease, why is the result negative?

This BRCA test is a germline genetic test that is only needed once in a lifetime. Currently, only approximately 10% to 15% of breast cancers involve a BRCA mutation, and there are other pathogenic genes that may lead to breast/ovarian cancer for which a larger PANEL testing package is recommended.

What is the difference between a negative and a positive test result?

A positive test result indicates a higher risk of disease. Depending on the test results, different medical tests would be recommended for different age groups, and the importance and treatment of some pathological signs would be different. There would also be a great difference in the methods, degree, and frequency of subsequent medical tests. In addition, the psychological stress to the subject is also different.

What are the implications of BRCA genetic testing?

BRCA testing may suggest if the subject may be at risk of hereditary tumor. It may also suggest if the subject should take appropriate preventive measures and live a healthy life to reduce the risk of a disease. BRCA testing also suggests that those at high risk should receive targeted health check-ups and early screening for early diagnosis and treatment as well as improvement of survival rate. For those with a family history, testing can relieve their psychological stress and prompt them to take scientifically sound preventative measures.

Does the presence of breast cancer have any effect on the results of genetic testing?

There is no effect. We perform germline genetic testing, which is determined at birth, and not tumor tissue testing. Whether or not you have breast cancer has no effect on the genetic test results.

How many people are tested positive?

The carrier rate of the BRCA pathogenic variants in the Chinese population is approximately 0.5%.

If the person already has the disease, how can a positive test result help the patient?

Individuals carrying BRCA1 or BRCA2 mutations are at a higher risk of developing new cancers, and knowledge of the BRCA gene status can help develop risk intervention plans or identify other potential tumor risks at the early treatment stage. Individualized targeted therapy exists for female patients with breast, ovarian, and pancreatic cancers and male patients with prostate and pancreatic cancers who carry deleterious germline mutations of BRCA. More importantly, the patients’ test results have significant implications for the health and prevention of the family members.

If the person carries a mutation in BRCA1 or BRCA2 gene but has no family history of ovarian or breast cancer, should they still be concerned?

Individuals carrying a BRCA1 or BRCA2 mutation are at a higher risk of developing breast and ovarian cancer, regardless of the presence of a family history. Therefore, it remains a concern.

Is BRCA genetic testing also available for men?

Although breast cancer is rare in men, men who carry the BRCA gene mutation are more likely to develop prostate, pancreatic, colon, and rectal cancer. Therefore, men can also be screened. In addition, a man who carries the mutation also has a 50 percent chance of passing on the mutation to his children, whether he has developed cancer or not.

What is the accuracy of BRCA genetic testing?

The accuracy rate of detecting germline pathogenic mutations is over 99%. The samples are tested using the MGISEQ-2000 high-throughput sequencer with a medical device registration certificate, and the detection region covers all coding regions of the BRCA1/2 gene. The germline variations are tested with an average sequencing depth of 200X or higher and a Q30 data ratio of 75% or higher, which is at the top international level. A sequencing depth of 200X or higher + a Q30 data ratio of 75% or higher + unique data analysis method ensures that the accuracy of the tested germline variation is above 99%.