Proliferating lists of genetic mutations linked to hereditary cancers have expanded the promise of more precise risk estimates and more targeted therapies, but they have also exacerbated the problem of how to judiciously offer, explain, and act upon the growing body of knowledge. That tension may be true everywhere. Multiple studies, though, have shown how it can be ratcheted up by cultural differences in perceptions of the prophylactic measures’ utility, in views of autonomy and privacy, and in decision-making among medical providers, patients, and their relatives.

In other words, what might seem to be a clear course of action in one country may be anything but in another. One overriding factor is whether such testing is even routinely offered. In Iceland, researchers tested all patients diagnosed with colorectal cancer over a decade for Lynch syndrome mutations.1 In China, however, a recent study found that genetic counseling services and routine molecular testing are still rarely available for patients believed to be at risk for the syndrome.2

Beyond availability, the degree to which medical providers can and do promote such tests to patients can vary widely by country. Cultural notions of the individual can likewise affect whether and how targeted genetic therapies are actively pursued. What constitutes freedom? Does it include not only the freedom to know about an inherited mutation that elevates the risk of cancer and about therapies targeting that mutation but also the freedom to not know? Moreover, what does autonomy mean in the context of different cultures where collective decision-making or even decisions in the absence of the patient are the standard?

A right to not know

In a small 2021 study from Switzerland, researchers interviewed 18 patients and two counseling physicians to examine how notions of autonomy influence decision-making over whether to undergo predictive genetic testing for hereditary breast and ovarian cancer syndrome or Lynch syndrome.3

All participating patients either had a family history of cancer or were previously diagnosed with it at a young age. Lead author Bettina M. Zimmermann, PhD, a postdoctoral fellow at the Institute for Biomedical Ethics at the University of Basel in Switzerland, says that the country’s Human Genetic Testing Act requires genetic counseling to be “nondirective” and emphasizes patients’ and family members’ “right not to know.” Swiss law also requires genetic counseling before and after predictive genetic testing from a specialized medical doctor. In contrast to the United States, such counseling is almost always performed by a medical geneticist, oncologist, or another physician instead of an accredited genetic counselor.

Three of the 18 patient participants refused genetic testing. As in the United States, Dr Zimmerman says, individual autonomy is highly valued, and she observed very little pressure among study participants to undergo the predictive testing. “Family did play a role in decision-making in the sense that they were often involved by the patient into the decision-making process. But the ultimate decision to get genetic testing is always made by the individual patient,” she says.

“Because each person has a right to know, but at the same time also a right not to know genetic risk information, this leads to potential dilemmas if individuals from the same family have divergent preferences,” Dr Zimmerman and her coauthors wrote. Some patients, she says, did take family interests into account even when they conflicted with their own preferences, such as performing a genetic test to help to clarify the potential risk for their children.

In a second study, Dr Zimmerman and her colleagues found that decision-making about whether to take the genetic test followed what they called a “control–fate continuum” based on the individual’s life philosophy.4 “Those in need [of] control decide differently compared with those leaving their future to fate,” she and her colleagues wrote. Even within Switzerland, the authors concluded, the study “illustrates the enormous interpersonal variability of the genetic testing decisionmaking process.”

As with other studies conducted around the world, however, Dr Zimmerman says that some cultural factors in Switzerland could potentially limit the applicability of her work elsewhere. In comparison with the United States, for example, “it is easier to say no to genetic testing,” she says. Although US physicians may generally recommend testing for cancer predisposition if they expect a medically actionable result, Swiss medical professionals are barred from making an explicit recommendation. “Instead, they would, in a neutral way, explain the risks and benefits of such a test, including potential future risks to privacy or discrimination, psychosocial risks, and preventive options available,” Dr Zimmerman says. That cautious neutrality with genetic technologies, she adds, is likely due less to perceptions of autonomy than to sensitivity over the history of eugenics in Nazi Germany.

A focus on family decisions

Decision-making elsewhere can be heavily shaped by other cultural values. In China, medical decisions and ethics are influenced by the belief system of Confucianism, usually involve the entire family, and sometimes occur without consulting the patient. In one survey study, 100% of US internists interviewed for the study and 90% of their counterparts in China said that they would tell a terminally ill patient about an AIDS diagnosis.5 In sharp contrast, 95% of the US internists but none of the Chinese internists would tell a patient with advanced cancer about the diagnosis. Furthermore, when family members’ preferences regarding the continuation of chemotherapy conflicted with those of a patient with advanced cancer, 65% of the Chinese internists sided with the family, whereas only 5% of the US internists did.

Family-weighted decision-making may influence how preventive care and the disclosure of positive genetic tests for hereditary cancers are handled as well. One recent study hinted at the largely unmet need for such testing in China: By screening tissues from nearly 4200 patients with colorectal cancer, the study estimated an overall Lynch syndrome prevalence of at least 2.7%, which was comparable to that found in Western populations.2 The retrospective study concluded that a selective strategy for Lynch syndrome screening should be considered for routine clinical testing.

Even when screening is widely available, concepts of autonomy, the right “not to know,” and other country-specific factors may heavily influence participation rates and thus the most effective strategies. A recent randomized trial of colon cancer screening among presumptively healthy men and women aged 55–64 years in Poland, Norway, and Sweden initially seemed to suggest a lower than expected benefit from colonoscopy.6 The big caveat, however, is that of those “invited” to receive the screening, only 42% acted upon it. If all invitees had undergone a colonoscopy, the researchers calculated, the lowered risks of colorectal cancer and colorectal cancer–related death would have been more on par with expectations.

Furthermore, the colonoscopy rates among “invited” study participants varied widely by country: from 61% in Norway to 40% in Sweden and 33% in Poland. Men were more likely to undergo screening than women in Norway and Poland, but not in Sweden. Although the study did not explain the sizeable difference, cancer screening programs likely would need to address it to maximize the benefits and to determine whether similar country-specific influences might present obstacles to predictive genetic testing.

Finally, the testing experience itself could influence whether a patient’s relatives decide to undergo testing. In the United States, most research on how genetic test results are communicated and received by patients has focused primarily on non-Hispanic White families who are mutation-positive for high-risk hereditary cancers. A 2019 study assessed the posttest reactions of patients at three cancer genetics clinics, including 26% who spoke only Spanish and 30% who had attained a high school education or less.

Roughly 80% of the patients wanted to know all their test results, even the variants of uncertain significance. For the most part, the study suggested, they were able to understand the results and did not regret having been tested. “It didn’t seem like overwhelming information,” says study coauthor Allison W. Kurian, MD, MSc, a professor of medicine, epidemiology, and population health at Stanford University in Palo Alto, California. “But I think it all depends on how people are counseled and what they have access to.”

If an overarching goal of predictive genetic testing is to expand risk stratification and medical interventions, providers may need to broaden their understanding of the cultural context of their patients and patients’ relatives and the many intertwining factors that help to guide decision-making.