Race and Cancer Genetics: Lessons From BRCA1

January 1, 2002

The study of cancer in specific populations can offer clues useful in determining the extrinsic and intrinsic factors influencing cancer in all populations. Extrinsic factors are sometimes called "environmental" in the broadest sense of the word. They are modifiable or mutable. Intrinsic factors are more inherent to the individual. They are almost always genetic and are immutable or unchangeable. Targeting research on specific populations is and should be a significant ethical issue.

The study of cancer in specific populations can offer clues useful indetermining the extrinsic and intrinsic factors influencing cancer in allpopulations. Extrinsic factors are sometimes called "environmental" inthe broadest sense of the word. They are modifiable or mutable. Intrinsicfactors are more inherent to the individual. They are almost always genetic andare immutable or unchangeable. Targeting research on specific populations is andshould be a significant ethical issue.

Incidence and cancer outcomes vary among populations, no matter how thepopulations are defined. The American medical literature commonly categorizespopulations by race or ethnicity. A few studies have even categorizedpopulations by socioeconomic status, area of geographic origin, or religion.Since 1994, the National Institutes of Health (NIH) has mandated that virtuallyall NIH-funded clinical research be conducted in such a way that"differences amongst the races and ethnicities can be determined," andit urges researchers to publish results by race, ethnicity, and gender.[1]

Population Categorization

It is unfortunate that we in medicine rarely think in rigorous fashion abouthow we divide and describe populations and what these divisions might imply.Very often, epidemiologic and clinical research using population categorizationswill demonstrate weak correlates with extrinsic influences on biology. Whenconducted using racial and ethnic categorizations, the findings can easily bemistaken as surrogates for, or evidence of intrinsic influences.

While it is true that the incidence and mortality of disease often vary byrace and ethnicity, neither is a biological categorization. Despite commonbelief, race does not equate with genetic homogeneity; rather, it is asociopolitical construct. Racial data, as such, often correlate with manysociopolitical factors that influence health. Ethnicity, while alsosociopolitical, is somewhat more scientific, as it can equate with culture andother environmental influences on health status.

The burgeoning fields of genetic and molecular epidemiology make itimperative that population categorization be better understood.Single-nucleotide polymorphisms, other genetic polymorphisms, and mutations canhave varying prevalences or frequencies among populations, however they aredefined. These differences in risk best relate to familial inheritance.

Indeed, virtually every genetic difference or polymorphism that has beencorrelated or associated with race should be considered familial and not racial.A specific gene or series of genes can be conserved among families. Family as acategorization clearly preserves genetic markers more efficiently than race orethnicity. A complicating factor is that race and ethnicity are also commonlypreserved by family.

Genetic Traits Within a Segregated Population

Much has been made of the higher prevalence of the 185delAG BRCA1 mutation inAshkenazi women. That there is a higher frequency compared to other populationsshould not be all that surprising. A closed society can conserve genetic traitswithin its populace. Segregation on the basis of race, ethnicity, religion,economics, or other factors can lead to an increased prevalence of a specificgene or series of genes in the segregated population. This has been demonstratedin a number of traits and diseases with a defined genetic basis, includingglucose-6-phosphate dehydrogenase (G6PD) deficiency, sickle cell disease, Tay-Sachsdisease, and cystic fibrosis.

Ms. Hoffman rightly notes that the specific mutations of BRCA1 and BRCA2associated with Ashkenazi Jewish women are not monopolized by them. This is alsotrue of many other genetic mutations associated with specific populations.Indeed, G6PD deficiency, sickle cell disease, Tay-Sachs disease, and cysticfibrosis all have higher prevalence in, but are not exclusive to, specificracial and ethnic groups.

Clinicians often use subtle clues in assessing an individual patient anddeveloping clinical suspicions. As such, a physician may perform a sort of"medical racial profiling." This is not wrong, evil, or unwise ifaccomplished with sensitivity and without attaching stigma. Unequivocalassumptions based solely on race, ethnicity, or other grouping should never bemade.


Ms. Hoffman presents a well thought-out discussion on genetic research indefined populations that can easily be expanded to other kinds of researchfocused on defined populations. Within the realm of scientific research, thegathering of data using well-defined population categorizations is reasonable,realizing the need for caveats in interpretation. It is useful to distinguishone group from another, provided the researchers are clear on the nature andsource of variations (eg, cultural, behavioral patterns, or other environmentalinfluences) and their relationship to health outcomes. Membership in a racial,ethnic, or other group may be associated with increased frequency of a specificgenetic marker as well as with behavioral and environmental factors that mayincrease or decrease the likelihood of an illness. Such research must beapproached with extreme caution, sensitivity, and forethought.


1. Freedman LS, Simon R, Foulkes MA, et al: Inclusion of women and minoritiesin clinical trials and NIH Revitalization Act of 1993—The perspective of NIHclinical trialists. Control Clin Trials 16(5): 277-285, 1995.