Hereditary cancer testing: who should test, how, and what it can miss

Hereditary cancer testing, also called cancer genetic testing, looks at your germline DNA: the DNA you were born with, the same in almost every cell. It checks for variants in genes where some changes are known to raise the chance of certain cancers. It doesn’t look for cancer itself, and it isn’t a diagnosis.

Most cancer isn’t inherited. NCI estimates that about 5% to 10% of all cancers are caused by harmful variants passed down from a parent.^[1] Testing speaks to that share, which matters most in families where cancer shows a pattern.

Much of inherited cancer risk traces back to a few well-known syndromes. This is background about genes and cancers. It isn’t a list of what any one test checks, and a gene’s name on a panel doesn’t mean every variant in that gene is checked.

• Breast and ovarian cancer. Harmful variants in BRCA1 and BRCA2 are the best-known cause. They also raise the risk of prostate and pancreatic cancer, and about 1 in 400 people carry one.^[2] BRCA1 and BRCA2 testing, explained; breast cancer genetic testing covers the genes beyond them.
• Colorectal (colon) and endometrial cancer. Lynch syndrome comes from a variant in MLH1, MSH2, MSH6, PMS2 or EPCAM, and about 1 in 279 people have it.^[3][4] Lynch syndrome, explained.
• Colorectal cancer with many polyps. Familial adenomatous polyposis comes from variants in APC and causes hundreds to thousands of polyps.^[5]
• Prostate and pancreatic cancer. These can run in families too, and BRCA1 and BRCA2 variants are among the inherited changes linked with both.^[2]

A result with no variant found can’t rule out inherited cancer risk.

NCI and CDC describe the patterns that suggest cancer in a family may be inherited. Any one of them is enough to raise with a clinician:^[1][6]

• Your own cancer diagnosis, now or in the past, or a close relative’s.
• A known variant in a cancer gene in any blood relative.
• Cancer diagnosed younger than usual in you or a relative: colon cancer before 50, for example.
• The same or linked cancers in several close relatives: breast with ovarian cancer, or colon with endometrial cancer.
• Two or more separate cancers in one person, or cancer in both organs of a pair, such as both breasts.
• An unusual cancer in the family, such as a man with breast cancer.
• Jewish ancestry from Ashkenazi or Eastern European communities, when breast and ovarian cancer also run in the family.

The U.S. Preventive Services Task Force (USPSTF) reviewed BRCA testing for women in 2019. It asks clinicians to check for a personal or family history of breast, ovarian, tubal or peritoneal cancer, or ancestry linked with BRCA1 or BRCA2 variants, and to refer women with raised risk for genetic counseling, then testing if indicated. It recommends against routine BRCA assessment and testing for women with none of that history.^[7]

A clinician-ordered test usually reads each gene in full and can look for missing or repeated pieces of a gene; an at-home test of selected variants checks only the variants on its list, so it can miss rare ones.^[9] If you or a close relative has had cancer, the clinical route is the one to start with. At-home or clinical testing? sets the two side by side.

• A variant found. A risk finding, not a diagnosis. If it came from a test of selected variants, ask your clinician to confirm it with a clinical test before any decision.^[10] After a positive BRCA result walks through the next steps.
• No variant found. Reassuring only for the variants the test checked. It doesn’t rule out inherited risk, and your family history still counts.
• An uncertain result. A variant of uncertain significance is one whose effect isn’t known yet. It isn’t a reason to act on its own; your clinician reads it alongside your history.^[1]

Prostate cancer can run in families too: harmful BRCA1 and BRCA2 variants raise its risk as well as that of breast, ovarian and pancreatic cancer.^[2] A father or brother with prostate cancer alongside breast, ovarian or pancreatic cancer in the family is a reason to talk to your clinician.^[1] Prostate cancer genetic testing covers the other genes, who should test and the limits.

GeneCancer, our at-home test of selected variants by genotyping, does not check RAD51C, RAD51D or HOXB13, genes that some clinician-ordered panels include.

A result with no variant found can’t rule out inherited cancer risk.

For people with no personal or family history of cancer, GeneCancer is our at-home option. Checks selected variants across 108 genes, including BRCA1 and BRCA2, by genotyping. It looks at chosen positions rather than whole genes, so a clinical test could find variants it misses, and a result with none found doesn’t rule out inherited risk. Take any variant it finds to your clinician to confirm with a clinical test.

Selected variants only, by genotyping. Not a full-gene test.

• Whether you have cancer now. It isn’t a diagnosis. If you have symptoms, see your doctor.
• Whether you will get cancer. A variant raises risk. It doesn’t decide the outcome.
• That you are in the clear. Only about 5% to 10% of cancers come from inherited variants,^[1] so whatever the result, the screening your clinician advises still stands.
• What to do next. Choices about screening, medicines or surgery are for you and your clinician, once any finding is confirmed.