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Vol. 02 Issue 4, Fall/Winter 1997

Family History and Breast Cancer Risk: Genetics, Lifestyle, Environment, or All of the Above?
The Ribbon 

Many women know that a "family history" of breast cancer presents a woman with an increased risk of breast cancer. Epidemiological studies tell us that having a "first-degree relative," - that is, a mother, sister, or daughter - who was diagnosed with breast cancer before age 60, means that a woman has twice the likelihood of developing breast cancer compared to a woman who has no first-degree relatives with the disease. If there are two first-degree relatives with breast cancer, a woman's risk is four to six times that of a woman with no first-degree relatives with the disease.

What explains the fact that breast cancer can "run in the family?" There have been dramatic recent advances in understanding several "breast cancer genes," including BRCA1 and BRCA2, and their range of possible mutations. With the publicity surrounding these findings, there may be a tendency to assume that strong family histories of breast cancer result from genetically inherited predisposition alone.

Scientists can confidently say that inherited genetic alterations account for 5 - 10% of breast cancer in the population. However, the prevalence of these genetic alterations among various populations is not well understood, nor is the actual lifetime risk of developing breast cancer for an individual carrier who has inherited a genetic alteration. Recent studies have resulted in a risk estimate much lower than previously thought for BRCA1 and BRCA2 mutation carriers. While earlier studies based on subjects from high-risk families produced lifetime risk estimates of 85% for BRCA mutation carriers, a newer study based on a wider community estimates the risk to be 56%.

When considering family history as a risk factor for breast cancer, there are many ways in which genetically inherited predisposition may be involved, including: the gene alterations mentioned above; other inherited syndromes such as one which causes increased sensitivity to ionizing radiation; or a risk factor like tallness, which has consistently been shown to be associated with breast cancer risk. Scientists are also studying other genes, such as those related to endogenous hormonal activity.

Cancer is always 'genetic' in that it involves the accumulation of mutations in key genes that control cell division. These mutations can be inherited, occur spontaneously when a cell makes a mistake in copying its DNA, or, can be induced by environmental agents. Therefore, there are other explanations for family clustering of breast cancer which may not involve inherited genetic predisposition. Other possible explanations which involve some established or possible environmental risk factors for breast cancer include:

1) Environmental, occupational, or household carcinogens to which multiple family members or generations may have been exposed. As in-progress epidemiological studies on breast cancer and environmental risk factors, such as the Long Island Breast Cancer Study Project and the Agricultural Health Study, begin providing results, more may be known about geographically-limited chemical exposures and breast cancer risk. These studies are taking extensive personal histories and analyzing a range of biological and environmental samples from participating households. These data will make a large contribution to what is known to date about pesticide and other chemical exposure and breast cancer risk.

The workplace and household are other possible sources of shared exposures to carcinogens. The National Toxicology Program (using animal studies) has identified 35 mammary carcinogens. These chemicals are found in a range of industrial, occupational, and household settings. Some of the mammary carcinogens include certain solvents, dyes, and pharmaceuticals. Further research is needed to identify the extent of exposure to these chemicals and any effects on breast cancer risk. Several studies have identified specific occupations that have a small increased risk of death due to breast cancer. These include female meat-wrappers, polyvinylchloride (PVC) fabricators, nurses and dental hygienists, printers and cosmetologists. Hopefully, these studies and other existing data will spur additional research which provide more information leading to policies resulting in reduced exposures.

2) Shared dietary patterns which either increase or decrease risk. Eating habits are closely tied to family and culture. Epidemiological studies have shown that certain diets are associated with increased or decreased breast cancer rates, and migration studies have shown that Asian women originating from populations with lower risk of breast cancer have an increased risk following migration to the U.S. Many researchers ascribe this shift to dietary changes, although other environmental factors have not been ruled out. With the many disparate food cultures in the U.S., it can be assumed that, to a certain extent, families share those aspects of diet that are either protective or increase the risk of breast cancer.

3) Other culturally-shared patterns of behavior, such as age at first birth and breastfeeding. The age at which a woman gives birth to her first child is associated with breast cancer risk (early first birth being protective). In recent generations, there may be a family pattern for age at the birth of the first child; for example, a family of highly educated women who delay childbearing. Likewise, a culturally-influenced practice such a breastfeeding may follow patterns in families. Some studies have found breastfeeding to be a protective factor against breast cancer. Patterns of weight gain in mid-life, which has shown to be associated with breast cancer risk, may also "run in families," due to certain dietary and physical activity patterns.

Breast cancer has multiple, interacting factors, and family members may share many of the genetic, reproductive, dietary, and environmental risk factors.

In their study of "Relative Weight, Weight Change, Height and Breast Cancer Risk in Asian-American Women," Regina G. Ziegler and her research associates found striking relationships between height and breast cancer risk, weight and breast cancer risk, and recent weight gain and breast cancer risk. Since this population's breast cancer risk differences cannot be explained by genetic predisposition, their study has important, immediate implications for risk reduction. They urge, "further examination of the complex interrelationships between body size and shape, diet, physical activity, and endogenous hormone levels ..."

Modifying factors - that is, those factors that influence whether or not another risk factor for breast cancer results in the disease for an individual - may play a role in whether a person who is genetically predisposed develops breast cancer. In a major study which resulted in lowered estimates of breast cancer risk for BRCA1 and BRCA2 carriers, the data suggests that there is much more variability than previously thought in whether a carrier develops breast cancer. What could explain this variability? The authors suggest that "(t)his variation may be due to chance, to genetic and environmental modifying factors, or to both. The study of families (who are carriers of BRCA mutations) with an apparently low risk of cancer may help elucidate such modifiers ..."

In discussing this and other recent BRCA1 and BRCA2 studies, Bernadine Healey, former director of the National Institute of Health, wrote in the May 15, 1997 New England Journal of Medicine, "(t)hese observations, taken together, underscore the role of modifying factors, whether genetic, hormonal, dietary or environmental, in determining whether a given BRCA mutation causes cancer."

These recent findings and hypotheses show that all the many types of research investigating the pathways to breast cancer - animal toxicological studies, the various types of epidemiological studies, as well as the mechanistic approaches, such as molecular genetics - all complement each other and are critical for eventual prevention of breast cancer, both in families with a strong history of breast cancer, and for those breast cancer cases that occur in women with no family history of the disease, which is greater than 85% of women who have breast cancer.

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Last Update 06.19.00