Hereditary Cancer
Hereditary cancer and cancer genetics
Overview
All cancers are caused by changes to materials in our bodies called “genes.” These are units of information in every cell of our bodies. Everyone has two copies of each gene, one from each parent. During development, genes tell our cells what type of tissue to become—a skin cell vs. a muscle cell, for example—and in later life, when to divide and make more cells. Genes also determine which proteins to make based on the type of cell and its needs. Some genes tell our bodies how to repair damage from environmental toxins, sun exposure, dietary factors, hormones, and other influences, or tell our cells when to stop growing.
When changes called “mutations” occur in the genes, certain cells can grow out of control and cause cancer. Gene mutations that can lead to cancer usually happen later in life. Over time, these changes occur as a result of the aging process, from exposure to things such as smoke, hormones, certain viruses, certain chemicals or from dietary influences. Not all damage to our cells leads to cancer, however, because our bodies have many methods for repairing damage and because we are all born with two copies of these damage-repairing genes.
When mutations occur in both copies of a gene and cannot be repaired, the damage can lead to uncontrolled growth of the cell, which can lead to cancer. Cancer usually develops slowly, often involving multiple steps (damage to multiple genes), over a period of several years.
What is hereditary cancer?
Hereditary cancers occur when a person is born with a change or mutation in a single copy of a protective gene pair. Because people with an inherited mutation have only one working copy of a protective gene, damage to that remaining gene may occur in fewer steps and over a shorter period of time. This change can increase the risk for certain cancers in different parts of the body. The medical community uses the term "genetic susceptibility" to describe the fact that people with an inherited mutation have an increased risk for cancer.
The change does not increase the risk for every type of cancer and not everyone who is born with a gene change will develop cancer; risks vary according to the exact mutation that was inherited. Many other factors affect the risk of cancer in someone born with a gene mutation. Scientists do not know all the factors that determine whether or not a person with a gene change will develop cancer over the course of his or her lifetime.
The term “hereditary cancer syndrome” describes an inherited gene mutation that increases the chance to develop one or more types of cancer. For instance, the main hereditary breast cancer syndromes—caused by mutations in the BRCA1 or BRCA2 genes—are also associated with an increased risk for ovarian cancer. The main hereditary colon cancer syndrome, called Hereditary Nonpolyposis Colorectal Cancer (HNPCC), can also be associated with an increased risk for ovarian cancer or uterine cancer. Other, more rare cancer syndromes can be associated with a wide variety of cancers.
Hereditary vs. sporadic cancers
Cancer is a common disease, so most families will have some members who have had cancer. We don’t know the cause of most cancer, but we do know that most cancer is not due to a single inherited change in a gene. Cancer that is not due to an obvious inherited pattern is called “sporadic cancer.” It is believed that most— perhaps 90%—of all cancers are sporadic. This means even if cancer does not run in a family, a family member can still be at risk for some type of cancer in his or her lifetime.
Sporadic cancer and hereditary cancer differ in several ways that may affect health care decisions:
- Hereditary cancer tends to occur at an earlier age than the sporadic form of the same cancer, so screening and risk-lowering recommendations for cancer may be different and may begin at an earlier age for members of a family with an inherited gene mutation.
- Multiple family members may have inherited the same gene changes which raise the risk for certain cancers.
- Hereditary gene changes can be passed on to children.
- Individuals who have inherited a gene change may be at a higher risk for more than one type of cancer. In people who have already been diagnosed with a cancer, this may affect their cancer treatment or follow-up care.
- Specific screening or risk-lowering options exist for individuals who know they are at high risk for certain types of hereditary cancer.
Signs of hereditary breast and ovarian cancer (HBOC)
Most cancer is not due to inherited mutations. About 10-15% of cancers are hereditary, depending on the type of cancer. Therefore, one or two cases of cancer in a family does not necessarily mean that there is a hereditary cancer syndrome in that family.
Many factors can help determine if the cancer in a family is hereditary, including the presence of certain types of cancer occurring in the same family (for example breast cancer and ovarian cancer, or colon cancer and uterine cancer); the age of onset of cancer (particularly with breast cancer and colon cancer, cancer diagnosed before age 50 is considered more significant); and the number of relatives with cancer and their relationship to each other.
Hereditary cancer risk can be passed down from either side of the family, so when looking at your family medical history, you need to consider relatives on both your mother’s and your father’s sides of the family.
When looking at a family history of cancer, genetics specialists like to examine at least three generations of medical history if that information is available. Cancer in a first-degree relative (parent, child, or sibling) holds more significance than a second degree relative (grandparent, grandchild, uncle, aunt, niece, or nephew). And cancer in a second-degree relative holds more significance than cancer in a third-degree relative (cousin, great-grandparent, great-aunt, or great-uncle). In general the closer the relationship between family members with cancer, the more significant the cancer may be in a family, however, experts also look at the overall pattern of cancer within a family going back several generations to determine the likelihood that the cancer is hereditary.
Several different cancer syndromes have been identified. For each there is a particular set of signs indicating the syndrome may be present within a family. It is important to speak with an expert in cancer genetics if you think there may be a cancer syndrome in your family.
FORCE focuses on the most common hereditary breast and ovarian cancer syndromes.
Signs of an hereditary breast-ovarian cancer syndrome may include but are not limited to:
- Breast cancer at age 45 or younger
- Breast cancer in both breasts in a woman at any age
- Both breast and ovarian cancer in the same woman
- Two or more family members with ovarian cancer and/or breast cancer, especially if the breast cancer was diagnosed at or before age 50
- At least one family member with breast cancer and one with ovarian cancer
- Breast cancer in men
- Ashkenazi Jewish heritage and ovarian cancer at any age or breast cancer before age 60
- A number of relatives on the same side of the family with breast or ovarian cancer and one of these cancers:
- Prostate cancer
- Pancreatic cancer
- Melanoma
Other factors may indicate a hereditary cancer syndrome within a family. It is important to seek the opinion of a specialist in cancer genetics if you believe the cancer in your family may be hereditary. For more information on finding a cancer genetics specialist, visit FORCE’s information section on this topic.
Other hereditary cancers
Changes in BRCA1 and BRCA2 are most closely associated with increased risk for breast cancer and ovarian cancer.
Other cancer syndromes can increase the risk for breast or ovarian cancer and may have other signs as well:
- Hereditary Non-Polyposis Colorectal Cancer (HNPCC) is a hereditary syndrome that can increase the risk for the following cancers:
- colon (particularly under age 50)
- ovarian
- endometrial (uterine)
- stomach
- small intestine
- bile duct
- Cowden Syndrome can increase the risk for the following cancers:
- breast
- thyroid (non-medullary)
- Cowden Syndrome can also cause distinct skin lesions
- Peutz-Jegher Syndrome can increase the risk for the following cancers:
- colon
- breast
- pancreas
- Peutz-Jegher Syndrome can also cause multiple pigmented spots on lips and inner cheeks
- Li-Fraumeni Syndrome can increase the risk for the following cancers:
- breast
- sarcomas (bony and soft-tissue)
- brain tumors
- childhood adrenocortical carcinomas
Other hereditary mutations have been identified that don’t increase the risk for breast or ovarian cancers but do increase the risk for other cancers. Any family with multiple individuals with the same cancer, very young onset cancers, or rare cancer types should consult with a genetics specialist regarding whether the cancer in family might be hereditary.
Additionally, there are families with multiple cases of breast cancer and/or ovarian cancer in which no mutation has been identified. These familial cancers likely have a hereditary component but the genetic cause has not yet been identified.
Other websites
In The Family
Developed by Kartemquin Films, the producers of the documentary In The Family, this website has links to articles and resources of interest to anyone concerned about hereditary breast and ovarian cancer
National Human Genome Research Institute
NHGRI is the division of the National Institute of Health (NIH) which focuses on research and resources related to genetics. The website contains links to a wide array of research and educational materials focused on genetics.
PDQ
(Physicians Data Query): Genetics of Breast and Ovarian
Cancer
Written for physicians, this summary covers the subject in depth. It is
updated monthly by the National Cancer Institute.
Talking Glossary of Genetic
Terms
Produced by the National Human Genome Research Institute.
Further reading - books
Am I Next in Line?
by Monique Achtman, a cancer pre-vivor and FORCE member. This book tells her family’s personal story and includes other families’ stories of hereditary cancer.
Apron Strings: Inheriting Courage, Wisdom and... Breast Cancer
by Diane Tropea Greene
Although dealing with a very serious topic, Apron Strings is an upbeat and optimistic look at what can be learned from the past, and all that the future has in store. When faced with adversity – faith, love, humor and the power of the human spirit will always prevail.
Blood Matters: From Inherited Illness to Designer Babies, How the World and I Found Ourselves in the Future of the Gene
by Masha Gessen
In 2004 genetic testing revealed that Masha Gessen had a mutation that predisposed her to ovarian and breast cancer. As she wrestled with a wrenching personal decision (what to do with such knowledge) Gessen explored the landscape of this brave new world, speaking with others like her and with experts including medical researchers, historians, and religious thinkers.
Positive Results
by Joi Morris and Ora Gordon, MD
One part memoir, three parts guidebook, Positive Results explains in a clear and steady manner the myths and realities of “the breast cancer genes.”
Pretty Is What Changes: Impossible Choices, The Breast Cancer Gene, and How I Defied My Destiny, by Jessica Queller
This book chronicles Jessica's journey with hereditary cancer in her family and genetic testing and highlights the difficult decisions that many living with hereditary cancer have had to face.
Further reading - articles (advanced reading)
Referral for cancer genetics consultation: a review and compilation of risk assessment criteria
Heather Hampel, K Sweet, J A Westman1, K Offit and C Eng.
Journal of Medical Genetics. Volume 41, Issue
2: p. 81-91, February 2004.
TGFBR1*6A
and cancer risk: A meta-analysis of seven case-control studies
Virginia G. Kaklamani, Nanjiang Hou, Yiansong Bian, Jennifer Reich,
Kenneth Offit, Loren S. Michel, W.S. Rubinstein, Alfred Rademaker,
Boris Pasche.
Journal of Clinical Oncology. Volume 21, Issue
17: p. 3236-3243, September 2003.
Frequency
of CHEK2*1100delC in New York breast cancer cases and controls
Kenneth Offit, Heather Pierce, Tomas Kirchhoff,
Prema Kolachana, Beth Rapaport, Peter Gregersen,
Steven Johnson, Orit Yossepowitch, Helen Huang,
Jaya Satagopan, Mark Robson, Lauren Scheuer, Khedoudja
Nafa, Nathan Ellis.
BMC Medical Genetics. Volume 4, Issue 1: p.1,
January 2003.
Breast
cancer genetics in African Americans
Olufunmilayo I. Olopade, M.B., B.S., James D. Fackenthal, Ph.D.,
Georgia Dunston, Ph.D., Michael A. Tainsky, MD, Ph.D., Francis Collins,
M.D., Ph.D., Carolyn Whitfield-Broome, Ph.D. Cancer. Volume
97, Issue S1: p. 236-245, December 2002.
A
CHEK2 genetic variant contributing to a substantial fraction of
familial breast cancer
Pia Vahteristo, Jirina Bartkova, Hannaleena Eerola, Kirsi Syrjäkoski,
Salla Ojala, Outi Kilpivaara, Anitta Tamminen, Juha Kononen, Kristiina
Aittomäki, Päivi Heikkilä, Kaija Holli, Carl Blomqvist,
Jiri Bartek, Olli-P. Kallioniemi, and Heli Nevanlinna.
American Journal of Human Genetics.
Volume 71, Issue 2: p. 432-438, August 2002.
Low-Penetrance
susceptibility to breast cancer due to CHEK2*1100delC in noncarriers of BRCA1
or BRCA2 mutations
The CHEK2-Breast Cancer Consortium. Nature Genetics.
Volume 1: p. 55-59, May 2002.