The Cancers People Don't Realize Can Be Hereditary
By Amanda Shrewsbury, MS, CGC
When most people hear the words "hereditary cancer," they automatically think of breast and ovarian cancer, and for good reason, but that association is also one of the biggest reasons people may miss the hereditary risk in their own family history.
Breast and ovarian cancer are the cancers most commonly linked to hereditary cancer risk by most, largely because of how well known the BRCA1 and BRCA2 genes have become. But hereditary cancer risk reaches much further than those two cancers. Prostate, pancreatic, colorectal, uterine, stomach, and even some melanomas can run in families, and the genes involved often connect several different cancers together in ways that are not obvious from the outside.
This matters because people frequently overlook their own risk. When the cancer in a family is colorectal or prostate or pancreatic rather than breast or ovarian, the hereditary connection may never come up, and an opportunity for earlier screening and prevention can be missed. This post walks through common cancers that can be hereditary, with plain-language red flags for each, drawn from current National Comprehensive Cancer Network (NCCN) genetic testing criteria. None of these red flags mean that a cancer is definitely hereditary. They are patterns worth discussing with a genetic counselor.
First, what makes a cancer "hereditary"?
Most cancers are not hereditary. The majority are sporadic, meaning they occur by chance and are not caused by an inherited factor. A smaller share are familial, where cancer clusters in a family more than expected but without a single identified gene. And a distinct subset, generally estimated at 5 to 10 percent of all cancers, are hereditary, caused by a specific pathogenic variant (a genetic change known to increase cancer risk) passed down through a family.
Hereditary cancers tend to leave clues. They often appear at younger ages than usual, show up in multiple relatives on the same side of a family, occur as more than one cancer in the same person, or cluster in particular combinations. Those patterns are what the red flags below are really describing. A single one does not confirm hereditary cancer, but it can be a reason to look closer.
Breast and ovarian cancer (the ones people expect)
We will start with the familiar, because it anchors everything else. Hereditary breast and ovarian cancer is most often associated with the BRCA1 and BRCA2 genes, which together cause Hereditary Breast and Ovarian Cancer (HBOC) syndrome. Other genes, including PALB2 and ATM, can also raise breast and ovarian cancer risk. We cover this in depth in our post on BRCA1 and BRCA2.
Red flags worth discussing with a genetic counselor, based on NCCN criteria, include breast cancer diagnosed at age 50 or younger, triple-negative breast cancer diagnosed at any age, ovarian cancer at any age, male breast cancer at any age, more than one breast cancer in the same person, several relatives on the same side of the family with breast or related cancers, and Ashkenazi Jewish ancestry, which carries a higher frequency of BRCA founder variants (a topic we explore in our post on Ashkenazi Jewish ancestry).
Colorectal cancer
Many people don't realize that colorectal cancer can be hereditary. It is one of the most important hereditary cancers, most often connected to Lynch syndrome, which is caused by variants in the mismatch repair genes (MLH1, MSH2, MSH6, PMS2) and EPCAM. Familial adenomatous polyposis (FAP), caused by the APC gene, is another hereditary cause. We cover Lynch syndrome in detail in our post on Lynch syndrome.
Notably, NCCN now recommends considering hereditary cancer testing for everyone diagnosed with colorectal cancer, a meaningful broadening from earlier guidelines that focused on younger patients. Red flags worth discussing include colorectal cancer diagnosed at a younger-than-usual age, multiple relatives on the same side of the family with colorectal cancer, colorectal cancer appearing alongside uterine or other related cancers in the family, and a known polyposis condition or a large number of colon polyps.
Uterine (endometrial) cancer
Uterine cancer, also called endometrial cancer, is one of the most clinically important hereditary cancers, and one that is often overlooked in conversations about family risk. For women with Lynch syndrome, uterine/endometrial cancer is often the first cancer to appear, sometimes before any colorectal cancer shows up in the family. It can be a sentinel event, the earliest sign that Lynch syndrome is present in a family at all.
Hereditary uterine/endometrial cancer is most often associated with Lynch syndrome, but another condition, Cowden syndrome, caused by mutations in the PTEN gene, can also raise uterine/endometrial cancer risk. Similar to colorectal cancer, NCCN recommends genetic testing for everyone diagnosed with endometrial cancer, regardless of age at diagnosis. Red flags worth discussing include uterine/endometrial cancer diagnosed at a younger-than-usual age, uterine/endometrial cancer occurring in the same person or family as colorectal or ovarian cancer, and a known Lynch syndrome variant in the family. Because uterine/endometrial cancer can be the first clue to Lynch syndrome, recognizing it as potentially hereditary can open the door to earlier screening for an entire family.
Pancreatic cancer
Many people don't realize that pancreatic cancer can be hereditary, and the connection is meaningful. It can be linked to BRCA1 and BRCA2, PALB2, ATM, the Lynch syndrome genes, CDKN2A, and others. NCCN recommends genetic testing for everyone diagnosed with pancreatic cancer, regardless of family history, which reflects how often a hereditary factor is involved. Our post on pancreatic cancer and genetic testing goes deeper.
Red flags worth discussing include any first-degree relative (a parent, sibling, or child) diagnosed with pancreatic cancer, two or more relatives on the same side of the family with pancreatic cancer, and pancreatic cancer appearing alongside breast, ovarian, or melanoma diagnoses in the family.
Prostate cancer
Prostate cancer is one of the most underdiscussed hereditary cancers, even though the connection is well established. It is most associated with BRCA2, and also with BRCA1, ATM, CHEK2, HOXB13, and the Lynch syndrome genes. The link to BRCA2 in particular means prostate cancer often belongs in the same family conversation as breast and ovarian cancer. We cover this in our post on men and hereditary cancer.
NCCN recommends germline genetic testing for men with high-risk, very-high-risk, regional, or metastatic prostate cancer, regardless of family history. Red flags worth discussing include metastatic prostate cancer, aggressive or high-grade prostate cancer, prostate cancer diagnosed at a younger age, and prostate cancer appearing alongside breast, ovarian, or pancreatic cancer in the family.
Stomach (gastric) cancer
Stomach cancer is one of the lesser-known hereditary cancers. The clearest hereditary connection is hereditary diffuse gastric cancer, caused by variants in the CDH1 gene, which is also linked to a specific type of breast cancer called lobular breast cancer. Lynch syndrome can also raise stomach cancer risk.
Red flags worth discussing, based on NCCN and international criteria, include diffuse-type gastric cancer diagnosed at a younger-than-usual age, two or more cases of gastric cancer in a family with at least one confirmed diffuse type, and diffuse gastric cancer appearing alongside lobular breast cancer in the same person or family. The connection between diffuse gastric cancer and lobular breast cancer is one of the clearest examples of how a single gene can link two seemingly unrelated cancers. NCCN now recommends multigene panel testing for individuals diagnosed with gastric adenocarcinoma at any age, though the recommendation carries a lower level of evidence for those diagnosed at age 50 or older.
Melanoma
Melanoma is the cancer almost nobody expects to be hereditary, but a subset is. The best-known hereditary connection is the CDKN2A gene, associated with familial atypical multiple mole melanoma (FAMMM) syndrome, which links melanoma and pancreatic cancer in the same families.
Per NCCN, genetic counseling for CDKN2A testing should be considered when an individual or family has more than two invasive cutaneous melanomas, or a mix of invasive melanoma, pancreatic cancer, and/or astrocytoma diagnoses. Red flags include multiple invasive melanomas in one person, melanoma appearing alongside pancreatic cancer or astrocytoma in the individual or family, and a first-degree relative with pancreatic cancer in a patient with invasive melanoma. It is also important to note that there are other genes associated with risk of hereditary melanoma.
Other cancers that can be hereditary
The cancers above are the most common, but hereditary risk can reach further still. Some hereditary syndromes connect a wider range of cancers. Li-Fraumeni syndrome (caused by the TP53 gene) is associated with a broad spectrum of cancers, often at young ages. Cowden syndrome (PTEN) raises the risk of thyroid, kidney, and other cancers in addition to breast and uterine. Multiple endocrine neoplasia syndromes are associated with endocrine cancers. We cover several of these less common genes in our post on hereditary cancer genes beyond BRCA1, BRCA2, and Lynch syndrome.
The broader point is that hereditary cancer is not limited to a short list. When cancer appears in a family in unusual patterns, it is worth asking whether a hereditary factor could be involved, regardless of the cancer type.
The red flags that apply across all hereditary cancers
If you take only one thing from this post, let it be the patterns that cut across every cancer type above. These are the signals that suggest a hereditary factor could be present, whatever the specific cancer:
- Cancer diagnosed at unusually young ages
- Multiple relatives on the same side of the family with the same cancer or related cancers
- The same person diagnosed with more than one separate cancer
- Specific combinations clustering in a family, such as breast and ovarian, colorectal and uterine, melanoma and pancreatic, or breast and prostate
- A known hereditary cancer variant already identified in the family
- Certain ancestries, such as Ashkenazi Jewish ancestry
Our guide to reading your family health history walks through how to spot these patterns in your own family.
What to do if any of this sounds like your family
Recognizing one of these patterns does not mean a cancer in your family is hereditary, and it certainly does not mean you will develop cancer. What it means is that a conversation could be worthwhile.
A genetic counselor can review your personal and family history in detail, help you understand whether a hereditary factor is likely, and talk through whether genetic testing makes sense for you. If testing is appropriate, the results can guide earlier and more effective screening, prevention options, and decisions for more family members. Our post on what happens during a genetic counseling appointment explains what to expect, and our post on cascade testing covers how a result can help relatives.
Knowing that certain cancers can be hereditary is the first step, because it turns a family history you might have overlooked into information you can act on, and that is exactly the kind of clarity a genetic counselor can help you find.
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References
National Comprehensive Cancer Network. (2026). NCCN clinical practice guidelines in oncology: Genetic/familial high-risk assessment — Breast, ovarian, and pancreatic (Version 3.2026). https://www.nccn.org/
National Comprehensive Cancer Network. (2026). NCCN clinical practice guidelines in oncology: Genetic/familial high-risk assessment — Colorectal, endometrial, and gastric (Version 1.2026). https://www.nccn.org/
National Comprehensive Cancer Network. (2025). NCCN clinical practice guidelines in oncology: Prostate cancer (Version 1.2025). https://www.nccn.org/
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This blog post is for educational purposes only and does not constitute medical advice, diagnosis, or treatment. Always seek the advice of your physician, genetic counselor, or other qualified healthcare provider with any questions you may have regarding a medical condition or your individual health needs.