Family Cancer Syndromes: Hereditary Risk and Family History

Introduction: Cancer and Inherited Gene Mutations

Cancer has become a common disease worldwide, and its prevalence is such that in many families at least one person has been affected. Researchers have noted that some forms of cancer tend to run in certain families. Often, common risk factors such as smoking — which can affect multiple family members — or obesity, which also tends to run in families, contribute to this pattern and have an influence on the prevalence of cancer within a family (American Cancer Society).

However, in some cases a set of abnormal genes passed along from generation to generation is the cause of cancer. While this phenomenon is often termed "inherited cancer," it is the defective or abnormal gene that is inherited, and which leads to the development of cancer in individuals of a particular family carrying that abnormal gene. Research has shown that cancers resulting directly from gene defects — called mutations — account for about 5% to 10% of all cancers (American Cancer Society).

DNA, Genes, and Chromosomes

Abnormal genes — pieces of DNA — are the cause of cancer. Genes carry information for cells to make the proteins the body needs, to destroy damaged cells, and to maintain the balance of cells in the body. All aspects of the human body, such as hair color, eye color, and height, are controlled by genes. The likelihood of developing cancer is also partly controlled and affected by genes.

A mutation is the term given to an abnormal change in a gene. There are two types of mutations, or changes in gene character: inherited and acquired. There are two copies of most genes — one from each parent — and cells start out with one mutation when there is a genetic abnormality. A cancer susceptibility gene is created when the other copy of the gene stops working due to an acquired mutation, which can lead to the development of cancerous cells and foster the growth of tumors.

Family Cancer Syndromes: When Should I Worry?

While certain causes of cancer running in the family could be due to bad habits like smoking, others are caused by an inherited gene mutation that results in a family cancer syndrome. Several indicators suggest that a family cancer syndrome may be present.

These indicators include: an uncommon or rare type of cancer such as kidney cancer; cancers that develop at a young age; multiple cancer types in a single individual, such as both breast and ovarian cancer in a woman; cancer developing in both paired organs, such as both kidneys or both breasts; more than one childhood cancer found in siblings; and cancer developing in the sex not usually affected, such as breast cancer in a man.

Family History and Prevalence of Certain Types of Cancer

After non-melanoma skin cancer, breast cancer is the most common and frequently detected cancer in women, and it causes more deaths than all other forms of cancer except lung cancer. Studies have found that among adult populations, 5% to 10% of women belong to a family in which either a mother or sister has or had breast cancer. The prevalence is doubled for women with either a first-degree relative (FDR) or a second-degree relative with breast cancer, as documented across case-control and cohort studies (Dungan).

Using volunteer and population-based samples, several studies have assessed the risk of developing breast cancer. Pooled findings from multiple studies indicate that the relative risk of breast cancer is 2.1, with a 95% confidence interval. The number of relatives affected by breast cancer, the age of an individual at diagnosis, the prevalence of bilateral or multiple ipsilateral breast cancers in a family member, and the occurrence of breast cancer in male relatives are all factors that increase an individual's risk of developing the disease (Colditz).

A study based on the Swedish Family Cancer Database found that women whose mother or sister has breast cancer run a significantly greater risk of developing the disease. That study found a hazard ratio of 1.8 for women with just one instance of the disease in the family, compared to a value of 2.7 for women belonging to a family with a history of multiple breast cancers (Kerber and O'Brien).

While reproductive complications, demographic factors, and lifestyle choices can all contribute to the development of ovarian cancer, a family history of the disease is one of the single most important risk factors. A large meta-analysis of 15 published studies found that the risk of ovarian cancer had a ratio of 3.1 in families with a history of the disease.

There have been frequent reports of familial clustering of prostate cancer, in a pattern similar to breast and colon cancer. High-risk inherited genetic factors and family history of prostate cancer susceptibility genes are believed to account for 5% to 10% of prostate cancer cases. Family history has been identified as a major risk factor for prostate cancer in large case-control and cohort studies representative of various populations (Friebel, Domchek, and Rebbeck). While the risk is increased by the prevalence of the disease in the family, it is inversely proportional to age — that is, families with a history of prostate cancer have a greater chance of developing the disease at a young age than the general population. Several population-based studies have examined risks associated with family history, and their data are considered generalizable (Chlebowski et al.).

A meta-analysis comprising 33 epidemiologic case-control and cohort-based studies found that men were at greater risk when their brothers had the disease than when their fathers were affected. X-linked or recessive inheritance is believed to be a possible explanation, although the precise reason for this difference in risk has not yet been determined. The number of close relatives affected by the disease has been found to be directly proportional to individual risk. The incidence of first-degree relatives being affected by prostate cancer before age 65 also increases an individual's risk directly.

The risk of a woman developing endometrial cancer is significantly influenced by family history, even though a hyperestrogenic state is considered the most common predisposing factor for the disease. Hereditary causes are believed to account for approximately 3% to 5% of uterine cancer cases in women (Weissman, Weiss, and Newlin). Lynch syndrome is the primary hereditary endometrial cancer syndrome and is believed to have a population prevalence of 1 in 300 to 1 in 1,000 individuals (Elfayomy and Soliman).

Conclusion

From the discussions above it can be concluded that the prevalence of certain types of cancer has been found to be linked to family history of the disease. The risk factor for breast, ovarian, prostate, and endometrial cancer is directly linked to a family history of the disease. However, the degree of risk depends on a number of factors within that family history, including the age of onset, sex, and the closeness or distance of the relationship between an individual and affected relatives.

References

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Chlebowski, Rowan T. et al. "Influence of Estrogen Plus Progestin on Breast Cancer and Mammography in Healthy Postmenopausal Women: The Women's Health Initiative Randomized Trial." Obstetrical & Gynecological Survey 58.11 (2003): 735–737. Web.

Colditz, Graham A. "Family History, Age, and Risk of Breast Cancer." JAMA 270.3 (1993): 338. Web.

Dungan, J.S. "The Decrease in Breast-Cancer Incidence in 2003 in the United States." Yearbook of Obstetrics, Gynecology and Women's Health 2008 (2008): 209–210. Web.

Elfayomy, Amr K., and Badeea S. Soliman. "Risk Factors Associated with the Malignant Changes of Symptomatic and Asymptomatic Endometrial Polyps in Premenopausal Women." J Obstet Gynecol India 65.3 (2014): 186–192. Web.

Friebel, T. M., S. M. Domchek, and T. R. Rebbeck. "Modifiers of Cancer Risk in BRCA1 and BRCA2 Mutation Carriers: Systematic Review and Meta-Analysis." JNCI Journal of the National Cancer Institute 106.6 (2014): dju091. Web.

Kerber, Richard A., and Elizabeth O'Brien. "A Cohort Study of Cancer Risk in Relation to Family Histories of Cancer in the Utah Population Database." Cancer 103.9 (2005): 1906–1915. Web.

Weissman, Scott M., Shelly M. Weiss, and Anna C. Newlin. "Genetic Testing by Cancer Site." The Cancer Journal 18.4 (2012): 320–327. Web.

American Cancer Society. "Family Cancer Syndromes." cancer.org, 2015. Web. 12 Nov. 2015.