BRCA Gene Testing Using 23andMe Raw Data
The earliest documented evidence of genetic predisposition for cancer is from the neuroanatomist Paul Broca. His detailed history of 15 members of his wife’s family with breast cancer courted controversy when it was published in 1866. However, with the advent of multi-gene testing panels, it is now possible to perform BRCA gene testing from DNA raw data containing the important BRCA polymorphisms. The raw data is primarily from ancestry genetic testing companies like 23andMe, Ancestry DNA, Family Tree DNA.
The US Food and Drug Administration approved the BRCA gene markers for 23andMe’s health reports in April 2017. These markers are common in people of the Ashkenazi Jewish population. These are more consumer testing than cancer screening reports. Raw data from 23andMe tests are not clinically certified. Increased cancer risk or lack thereof from these reports must be validated using clinical diagnosis.
Prevalence of Breast Cancer:
About one in eight women have a chance of developing breast cancer during an 80-year lifespan. Out of this, 5 to 10% may be due to hereditary factors. Another 10 to 30% may be due to familial inheritance. About 60 to 85% of sporadic cancers develop due to many other factors.
NOTE: A negative result is not absolute. Meaning it does not infer that you are completely immune from developing breast cancer. At the same time testing positive for BRCA genes does not imply that you will develop breast cancer.
Find out more about why you need to take up genetic testing for breast cancer here.
Xcode’s BRCA test from ancestry DNA raw data
Xcode’s BRCA gene testing from the 23andMe DNA raw data panel targets genes which are associated with cancer susceptibility. This includes high penetrance, FDA authorized genes like BRCA1, BRCA2, TP53 as well as genes that have middle and low penetrance levels. These markers are common in people of Ashkenazi Jewish descent. The test can potentially identify the risk for breast cancer. This information can be used to develop personalized screening schedules and preventive strategies to reduce risk. Taking a genetic counseling session using this report can prove very useful.
The report includes the following aspects:
- BRCA Gene Testing and Predisposition to Breast Cancer
Genome-Wide Association Studies (GWAS) have helped in identifying multiple genes associated with an increased risk of developing breast cancer. If you carry many of these high-risk genes then you have an increased risk of developing breast cancer, compared to the general population.
The risk for the following different types of breast cancer can be identified from the BRCA gene testing report:
- Breast cancer risk
- Estrogen Receptor Positive Breast Cancer Risk
- Estrogen Receptor Negative Breast Cancer Risk
- Breast and Ovarian Cancer Risk
- Breast and Other Cancer Risk
- Early Onset Breast Cancer
Read more about predisposition to breast cancer here
- BRCA Gene Testing and Genetic Prognosis:
Prognosis varies between individuals, though the type of cancer may be the same. This may be indicative of genetic aspects. Identifying the extent of genetic influence in prognosis will help plan a better treatment strategy.
Read more about breast cancer prognosis here
- BRCA Gene Testing and Breastfeeding Duration and Breast Cancer Risk
Breastfeeding duration is also associated with the gene variants that an individual carries. The heritability of breastfeeding duration ranges between 44-54%. This is another critical factor in the risk for breast cancer. Increased breastfeeding duration lowers lifetime exposure to estrogen, thereby the risk for breast cancer. Understanding the genetic tendency to breastfeed will help in altering feeding duration to lower risk.
Read more about Breastfeeding duration and breast cancer risk here.
- BRCA Gene Testing and Breast Size and Breast Cancer Risk
The morphology of the breast is associated with breast cancer. The genetic variants which are associated with an increased breast size (non-fat breast tissue) are also indicated in breast cancer. The heritability of breast size is 54%. A lean woman with a breast size of D has 1.8 times increased risk of breast cancer. Understanding the tendency to have an increased breast size will help in structuring personalized exercise routines to lower breast size.
Read more about breast size and breast cancer risk here.
- BRCA Gene Testing and Menopausal Hormone Therapy and Breast Cancer Risk
Menopausal hormone therapy is commonly used by peri and postmenopausal women to overcome symptoms of menopause. Women with certain genetic variants are associated with a higher risk of breast cancer on menopausal hormone therapy. Women with more than 5 or 6 high-risk variants in specific genes were found to have an 86% increased risk for breast cancer on the recent use of menopausal hormone therapy. Understanding the genetic variants carried will help in utilizing menopause symptom reducing strategies that do not increase the risk for breast cancer.
Read more about menopause hormone therapy use and breast cancer risk here.
- BRCA Gene Testing and Hormone Plasma Levels and Breast cancer Risk
Some female hormones have been associated with an increased risk for breast cancer. The level of this hormone decreases drastically postmenopause. However, women with certain genetic variants continue to have increased levels of this hormone even after menopause. Identifying the genetic variants present in an individual will help in determining the plasma levels of female hormones. This will help to deduce unique hormone therapy to lower the level of this hormone and thereby lower the risk of breast cancer.
- BRCA Gene Testing and Breast Cancer Risk In Men:
About 1% of men have an elevated risk for breast cancer. Identifying this risk will help in determining the most effective treatment strategy to lower risk. A woman with an affected brother has a 30% higher risk of developing breast cancer than if her sister was affected.
- BRCA Gene Testing and Chemotherapy and risk of Hypertension:
Chemotherapy has been associated with hypertension but the extent of hypertension is variable and has a genetic aspect. Identifying the risk for hypertension will help in determining suitable treatment strategies. This can be done by BRCA gene testing from Ancestry DNA raw data.
- BRCA Gene Testing and Chemotherapy and risk of alopecia:
Most women find it hard to control hair loss in their battle against breast cancer. Identifying the risk for alopecia on chemotherapy will help in developing more suitable treatment strategies or in better coping mechanisms. It is possible to estimate the risk for alopecia using BRCA gene test results based on DNA raw data.
- BRCA Gene Testing and Response to Chemotherapy
Pharmacotherapeutic studies have been successful in identifying genetic variants that are associated with the susceptibility, toxicity, and efficacy of chemotherapeutic drugs. Using BRCA gene testing from DNA raw data from companies like 23andMe and Ancestry DNA has picked up. It may help identify the genetic response to chemotherapeutic drugs. This will also help in developing personalized treatment plans using drugs that have optimum efficiency with relatively lower toxicity.
As a sign-off note, BRCA and breast cancer are best interpreted and explained by a genetic counselor. Visit your genetic counselor to get the maximum benefits from your BRCA report.