Comprehension of skin cancer genetic risk feedback in primary care patients

Abstract

Few studies have examined comprehension and miscomprehension of genetic risk feedback for moderate-risk genes in the general population. We examined the prevalence and nature of accurate and inaccurate genetic risk feedback comprehension among those who received genetic testing for melanocortin-1-receptor (MC1R) gene variants that confer moderate melanoma risk. Participants (N = 145 Albuquerque, NM) were tested as part of a randomized controlled trial. Two weeks after receiving MC1R genetic risk feedback, participants answered open-ended questions regarding their reactions to the MC1R feedback report. Participants’ comprehension of their feedback (average-risk or higher-risk for melanoma) was evaluated through qualitative analysis of open-ended responses. Most participants demonstrated comprehension of their feedback results (i.e., 63% of average-risk participants [ARPs]; 51% of higher-risk participants [HRPs]). Miscomprehension was evident in fewer participants (i.e., 16% of ARPs, 11% of HRPs). A few ARPs misunderstood the purpose of testing, whereas a few HRPs reported confusion about the meaning of their risk feedback. Some participants’ responses to the open-ended questions were too ambiguous to ascertain comprehension or miscomprehension (i.e., 21% of ARPs, 38% of HRPs). Taken together, these findings suggest that genetic testing feedback for MC1R risk variants is largely comprehensible to general population participants. This study adds to the work examining comprehension and usage of common, moderate risk genetic information in public health contexts. However, to maximize the utility of genetic risk information in the general population, further research is needed to investigate and address areas where common genetic risk feedback misunderstandings occur.

Supplementary Information

The online version contains supplementary material available at 10.1007/s12687-021-00566-9.

Introduction

The process of genetic sequencing is more efficient and cost-effective than ever before, increasing the availability of genetic testing to the general population (Horton and Lucassen 2019). Through genetic testing, individuals can receive information about disease risk. While traditionally, the focus of genetic testing was to determine the presence of rare, highly penetrant mutations that confer significantly increased risk for certain diseases; now, members of the general public have greater access to testing for relatively common gene variants that confer modestly increased risk for more prevalent diseases (Berberich et al. 2018). Though widespread availability of genetic testing and risk feedback may empower those tested with increased health risk awareness and motivation to improve their health through risk-reducing behavior changes (Schaper and Schicktanz 2018; Frieser et al. 2018), there is also concern that individuals may misunderstand their results, potentially leading to distress, misuse of limited healthcare resources, or disregard of relevant risk information (Hamilton and Robson 2019; Frueh et al. 2011).

Several recent studies have shown that genetic risk feedback can be highly comprehensible to the general population (Kaphingst et al. 2012; Kaufman et al. 2012; Ostergren et al. 2015). However, comprehension may vary by type of result received. For instance, in a study by Lipkus et al. (2004), genetic risk feedback was provided to smokers concerning whether they were average- or high-risk for lung cancer based on glutathione S-transferase Mu 1 (GSTM1) genetic testing. Those who received high-risk feedback were more likely to inaccurately recall their results compared to those who received average-risk feedback, which the authors attribute to defensive processing of threatening information. Receipt of higher-risk feedback may elicit more disbelief or confusion than average-risk feedback, especially when risk implicates common habits and preferred behaviors. In a study conducted by Aktan-Collan et al. (2001), participants were offered testing for MutL homolog 1 (MLH1) gene mutations associated with 80–90% lifetime risk of colon cancer. One month after results receipt, those who received mutation negative findings had a significantly higher rate of accurate comprehension of colon cancer risk feedback compared to those who were mutation positive. The aforementioned study examines comprehension of genetic risk feedback provided after testing for mutations associated with significantly increased disease risk. However, genetic testing for relatively common gene variants associated with modestly increased disease risk is increasingly available to the general population. Few studies have examined comprehension of genetic risk feedback for mutations that confer only moderately increased disease risk.

In the current study, we examine comprehension of skin cancer risk feedback for the melanocortin-1 receptor (MC1R) gene. The presence of any variant of the MC1R gene is associated with moderately increased melanoma risk. Such variants are frequently occurring, found in the majority (~ 60%) of individuals of European descent (Pasquali et al. 2015). Across varied populations with European ancestry, including those with darker pigmentary phenotypes, nine frequently occurring MC1R variants have been identified that are associated with a 1.5- to 2.7-fold increased risk of developing melanoma (Pasquali et al. 2015). As such, provision of feedback on MC1R variants presents an opportunity for relevant, actionable skin cancer risk information for large segments of the general population (Kanetsky and Hay 2018).

Our study aim is to describe responses related to comprehension and miscomprehension of MC1R genetic risk feedback two weeks after receipt. While prior studies have found generally high levels of risk feedback comprehension (Kaphingst et al. 2012; Kaufman et al. 2012; Ostergren et al. 2015; Molster et al. 2009), we focused on describing any miscomprehension based on whether participants received average- or higher-risk feedback.

Materials and methods

Participants

This study was part of a randomized controlled trial that examined uptake and utility of genetic testing (R01 CA181241, Hay/Berwick, MPIs), where primary care patients were offered genetic testing for MC1R gene variants. Participants were eligible for the trial overall if they were registered as patients in University of New Mexico (UNM) outpatient primary care clinics for at least six months, assigned a UNM primary care physician, aged ≥ 18 years, and fluent in English or Spanish (Hay et al. 2018). The participants included in the current study were those randomized to receive a genetic testing offer, who then chose to get tested, and later completed a comprehension assessment regarding their genetic testing results (N = 145).

As reported previously (Kaphingst et al. 2021), participants who underwent testing (N = 145) ranged in age from 23 to 79 years (mean age 55 years); most (79.3%) were female; 64% were non-Hispanic White, 32% were Hispanic, and 4% were of other racial/ethnic backgrounds; about half (55.8%) had an income of less than $50,000; about 10% had a high school degree/GED or less, 21% had some college, and 70% had an associate degree or higher.

Procedure

Eligible individuals who accepted participation in this trial were randomized 1:5 to a wait list control condition (n = 101) or an intervention condition (i.e., offer of genetic testing for MC1R, n = 499). Participants who were randomized to receive an offer of MC1R genetic testing were invited to log onto the study website to review pretest educational materials, consisting of three modules available in English or Spanish, regarding skin cancer and MC1R testing (see Appendix A for pretest materials). After completing these modules, participants registered their decision on whether they wanted MC1R testing. Participants could only elect testing after reviewing the educational modules. Participants who chose genetic testing were mailed a test kit and could provide a saliva sample for testing.

Participants who underwent genetic testing as part of the trial (Hay et al. 2018, 2017) received a results report with their genetic risk feedback (either average-risk feedback, based on the presence of no MC1R variants associated with melanoma risk; or higher-risk feedback, based on the presence of at least one MC1R variant [Rodríguez et al. 2017]; see Appendix B for the results report). This feedback was designed using plain language and clear communication guidelines, modeled after the Multiplex Initiative (Kaphingst et al. 2012), and adapted for the current trial through further cognitive testing (Kaphingst et al. 2021; Rodríguez et al. 2017). Participants were contacted by study staff to complete a comprehension assessment 2 weeks after receiving results, and the participants who completed this assessment (N = 145) represented the analytic sample for the present study. The UNM Institutional Review Board approved all study procedures and materials, and all participants provided written informed consent.

Data analysis

Participants’ comprehension of their MC1R genetic risk feedback was ascertained using their spontaneous responses to the following open-ended prompts: (1) “Please tell me the most important thing you remember from the report.”; (2) “Anything else you thought was important?”; (3) “People can have different reactions to genetic test results. …In your own words, how did you feel about getting your test results?”.

Participants’ responses were recorded verbatim. Response data were coded with respect to comprehension dimensions. The analysis team consisted of three trained qualitative coders (JB, SC, EK) to achieve analyst triangulation, a strategy to increase validity of results via use of multiple investigators who separately interpret data and then cross-verify results (Denzin 2009). The team met to collaboratively define the following coding categories: “comprehension of results” and “miscomprehension of results.” Comprehension of genetic test results was established if (1) a participant correctly noted whether they had an MC1R gene variant and/or (2) whether their results indicated they were at average or higher risk for melanoma, and (3) when a participant did not show “Miscomprehension” (outlined next). Miscomprehension was established if a participant had an erroneous understanding of any of the following: (1) whether they had a MC1R gene variant, (2) whether their results indicated they were at average or higher risk for melanoma, or (3) the purpose of MC1R genetic testing. Participants whose spontaneous responses to the aforementioned questions were too brief or vague to ascertain their level of comprehension were coded to a third category, “unable to determine comprehension.” The coders independently applied these coding categories to transcripts of each participants’ responses to open-ended questions. Then, they met to compare and reconcile discrepancies. The frequency and percentages of all coding categories were calculated.

Next, team members reviewed the data using a thematic analysis approach to explore comprehension of MC1R genetic risk feedback in depth (Kvale and Brinkmann 2009; Patton 2015). They independently reviewed the interview data to identify themes, based on frequency and saliency, regarding comprehension of MC1R genetic test results. Themes were identified within each of the two risk feedback groups (average-risk participants [ARPs] and higher-risk participants [HRPs]), as well as across the entire sample. Finally, the team met to discuss their independently identified themes and to resolve any discrepancies. During this meeting, the team created a final consensus list of themes and selected representative quotes (Table 1). Themes that emerged are described below, both across risk feedback groups, as well as those that are unique to either the average- or higher-risk feedback groups.

Table 1.

Themes, subthemes, and selected quotes related to comprehension of MC1R genetic test results (n = 145)

Theme	Risk feedback group	Subtheme	Representative quotes
Most participants, comprehended their results	Across risk feedback groups	(None)	“I do not have a risk type and I have a 1 in 100 risk of getting skin cancer.” (ARP) “I have a greater possibility for skin cancer—3 times the general population.” (HRP)
A few misunderstandings of results were noted	Across risk feedback groups	Some believed that MC1R testing indicated the presence/absence of a gene	“I do not have the gene that was being screened for.” (ARP) “I have the gene related to a increased skin cancer risk.” (HRP)
		Some had deterministic thinking, believing results indicated whether one is susceptible or predisposed to melanoma	“I’m not susceptible to melanoma.” (ARP) “I’m predisposed to melanoma.” (HRP)
		Some incorrectly recalled their results	“(I) am not average risk.” (ARP) “Glad to see I wasn’t higher risk.” (HRP)
	Average-risk participants	Some misunderstood the purpose of MC1R genetic testing, considering it a diagnostic or predictive test	“I don’t have skin cancer.” (ARP) “I was not going to get skin cancer- I’m average risk.” (ARP)
	Higher-risk participants	Some voiced confusion about the risk feedback report, with some expressing difficulty finding relevant information and others with interpreting statistics	“I was confused. I didn’t see my risk factor or understand where to find my risk results.” (HRP) “That I was 3 out of 100. I wasn’t quite sure what it means.” (HRP)

Note: ARP = average-risk participant, HRP = higher-risk participant

Results

Comprehension

The majority of participants (n = 81/145, 56%) accurately comprehended their results, with 63% (n = 36/57) of ARPs and 51% (n = 45/88) of HRPs falling into the “comprehension” category. As such, most participants expressed understanding of whether their MC1R genetic testing results indicated they had an MC1R gene variant and/or whether they were at average or higher risk for melanoma. For example, one ARP stated, “I have an average risk for getting skin cancer” while another ARP said, “I do not have a risk type and I have a 1 in 100 risk of getting skin cancer.” In a similar vein, a HRP stated, “I have a greater possibility for skin cancer – 3 times the general population.”

Additionally, many participants indicated accurate comprehension that MC1R gene variants were associated with a modest increase in melanoma risk. For example, one HRP stated, “I have a higher than average likelihood of developing skin cancer. Though the percentage of likelihood was small, it was important to note that it was higher than normal.” Many participants spoke to their understanding that MC1R genetic test results provided information about susceptibility towards melanoma, but that it was not deterministic. Indeed, participants often acknowledged other factors that contributed to melanoma risk (e.g., lack of sun protection). For example, one HRP stated, “I am at higher risk for skin cancer…It confirmed what (I) suspected. And I am more conscious now of making sure that I am as protected as possible.”

Miscomprehension

Overall, few participants reported elements of miscomprehension (n = 19, 13% overall; n = 9/57, 16% of ARPs; n = 10/88, 11% of HRPs). Some types of miscomprehension were seen across both average and higher risk groups; several participants indicated their belief that MC1R genetic testing detected the presence or absence of a gene. For example, one ARP said, “I do not have the gene that was being screened for,” while a HRP commented, “I have the gene related to a(n) increased skin cancer risk.” In a related way, some thought they were either susceptible or not susceptible to melanoma. Finally, across risk feedback groups, a few participants incorrectly reported their result category. For example, an ARP stated “(I) am not average risk,” while a HRP said they felt “glad to see I wasn’t higher risk.”

Miscomprehension by risk feedback group

Average-risk feedback

The quality of misunderstanding differed to some extent between the two groups. Among ARPs, a relatively common misunderstanding involved the purpose of MC1R genetic testing. A few ARPs incorrectly believed that it was a diagnostic test for current melanoma, making comments like, “I don’t have skin cancer.” A few others in this risk feedback group believed the test definitively predicted whether they would develop future melanoma, with statements like, “I was not going to get skin cancer. I’m average risk.”

Higher-risk feedback

Several HRPs voiced confusion about the meaning of their results. A few of these HRPs were confused by the way the information was presented, with one HRP saying, “I was confused. I didn’t see my risk factor or understand where to find my risk results.” A few other HRPs found it difficult to interpret the probabilities presented, making statements like, “I was 3 out of 100. I wasn’t quite sure what it means.”

Unable to determine comprehension

Some participants (n = 45, 31% overall; n = 12/57, 21% of ARPs; n = 33/88, 38% of HRPs) offered responses to the open-ended prompts that did not contain enough information to cleanly categorize them as either comprehending or miscomprehending the results of their MC1R genetic testing, and these individuals were assigned to the category “unable to determine comprehension.” Such responses included information not relevant to comprehension per se, with an ARP saying, “Everything was fine” and a HRP saying, “I have risk.”

Discussion

As interest in and uptake of testing for common gene variants increases in the general population, it is important to examine and understand the nature of potential patterns of miscomprehension of genetic risk feedback. In the current study, 56% of all participants (63% of ARPs and 51% of HRPs) who received MC1R genetic test risk feedback correctly interpreted their feedback. These participants correctly reported whether they had an MC1R gene variant and/or whether they were at average or higher risk for melanoma. Many correctly understood that the presence of MC1R gene variants did not indicate that they would develop melanoma with certainty, but that sun protection would be important in reducing their future risk, consistent with other recent work clarifying accurate comprehension of relative risk levels (Kaphingst et al. 2012; Kaufman et al. 2012) as well as perceptions of combined genetic and environmental risks of disease (Hoell et al. 2021).

While uncommon, the most frequently noted misunderstanding involved participants stating that they “have” or “do not have the gene.” This response may reflect common limited understandings of genetic principles underlying genetic testing for disease risk (Smerecnik et al. 2008). Participants may not understand that testing was for variant forms of the MC1R gene, rather than the presence or absence of the gene itself, despite the provision of written information that clarified this fact. On the other hand, these interpretations may also reflect essentialist language, or the use of easier to produce “unqualified, direct sentences” rather than “qualified, multicausal sentences” (Condit 2019). Essentialist language is often used in mainstream media and communication among laypeople, such as the use of the “BRCA gene” as a shorthand substitute for “risk-increasing variant of the BRCA gene” (Condit 2019). Therefore, it is possible that some of the participants who stated they “have” or “do not have the gene” may have been choosing to use simplified speech, while still implicitly understanding their genetic test results that indicate whether they “have” or “do not have a risk-increasing variant of the MC1R gene.”

When clinicians deliver genetic risk feedback information, it is important to acknowledge that patients may prefer to use verbal presentations and lay terms rather than relying on numeric explanations of risk. As Condit explains, some scientists employ a “deficit model” and presume experts, who often rely on statistics to share risk, have the correct approach rather than laypeople (Condit 2010). However, in a qualitative study examining how healthy participants make sense of genetic risk information, Viberg Johansson and colleagues found that many laypeople consider genetic risk as a binary concept, where “either you have risk or you don’t” instead of considering risk in terms of numeric probabilities (Viberg Johansson et al. 2018). This may explain why some individuals in “unable to determine comprehension category” of the present study made vague statements, like “I have risk.” Viberg Johansson and colleagues suggest that laypeople’s understanding of genetic risk as a binary concept may not be an irrational miscomprehension, but rather a heuristic strategy that facilitates health decision-making (Viberg Johansson et al. 2018). In the future, it may be beneficial for researchers and clinicians to develop effective verbal presentations of genetic risk for the general population that incorporate lay terms rather than relying on numeric explanations of risk.

Interestingly, a greater proportion of HRPs compared to ARPs were coded as “unable to determine comprehension” (38 vs 21%, respectively). This may reflect efforts by higher-risk individuals to downplay their risk in order to avoid threatening emotions such as fear, rather than to adopt precautions to address their higher risk (Witte 1992, 1994). Those participants who have vague, noncommittal responses may be choosing a defensive strategy (Witte and Allen 2000). While only a minority (n = 19, 13%) miscomprehended their risk, ARPs who miscomprehended their findings showed optimism about not having melanoma currently, which may reflect misinterpretation of average risk feedback as a negative diagnostic finding (Stuttgen et al. 2020). In contrast, HRPs who misinterpreted their findings reported confusion, trouble navigating the risk feedback report, or difficulty understanding probabilistic information on melanoma risk. This is consistent with work showing that misunderstandings about statistics and genetics can fuel each other; minimization and denial can further bolster these misunderstandings in those who receive higher-risk results (Klitzman 2010). Adequate numeracy facilitates the accurate interpretation of statistics (U.S. Department of Education 2017); however, a significant proportion of the US population (29%) has low numeracy. As such, it may be beneficial to tailor post-test counseling based on risk feedback type; ARPs may benefit from counseling that clarifies that their results do not indicate lowered disease risk, whereas HRPs may benefit from additional support managing emotions and interpreting statistics.

Our study is limited in that the use of open-ended prompts may have not fully explicated elements of comprehension of MC1R genetic testing feedback. However, our strategy was useful in identifying the most salient elements of testing in participants’ perspective. Future studies could include both quantitative and qualitative items to comprehensively assess comprehension of MC1R genetic risk feedback. A major strength of this study involved its greater diversity, both ethnically and socioeconomically, compared to many other translational genomic studies, which enhances the generalizability of results (e.g., Suther and Kiros 2009; Bloss et al. 2011; Hensley Alford et al. 2011). However, the sample being studied has a relatively high level of education compared to the general population, which may limit the generalizability of results. Another strength of this study is the use of plain language and clear communication principles in developing the risk feedback materials sent to our participants, which may have helped with comprehension (Kaphingst et al. 2021).

Conclusion

Our results corroborate previous studies that suggest that the general population has a high level of comprehension of genetic risk feedback, since a large proportion understood the results of MC1R for melanoma risk, regardless of risk feedback type. Though the majority of participants demonstrated comprehension of their genetic risk feedback, this study identified some misunderstandings that limited comprehension of results, including misperceptions that differed by feedback type. These findings, which provide useful information on how comprehension differed by risk status, may help dictate educational needs to tailor delivery of genetic risk information, optimizing the use of feedback regarding moderate genetic risk in primary care and public health settings.

Supplementary Information

Below is the link to the electronic supplementary material.

Author contribution

Erva Khan: conceptualization, investigation, writing—original draft. Kimberly A. Kaphingst: conceptualization, investigation, writing – original draft. Kirsten Meyer White: data curation, investigation, project administration, writing—review and editing. Andrew Sussman: investigation, writing—review and editing. Dolores Guest: investigation, writing – review and editing. Elizabeth Schofield: formal analysis, visualization, writing—review and editing. Yvonne T. Dailey: investigation, writing—review and editing. Erika Robers: data curation, investigation, project administration, writing—review and editing. Matthew R. Schwartz: investigation, writing—review and editing. Yuelin Li: formal analysis, methodology, visualization, writing—review and editing. David Buller: investigation, writing—review and editing. Keith Hunley: investigation, writing—review and editing. Marianne Berwick: funding acquisition, investigation, supervision, writing—review and editing. Jennifer L. Hay: conceptualization, funding acquisition, investigation, supervision, writing—original draft.

Funding

This study was supported in part by the National Cancer Institute’s Research Grant (R01 CA181241), Support/Core Grant (P30 CA008748), and Training Grant (T32 CA009461). This research was partially supported by UNM Comprehensive Cancer Center Support Grant NCI P30CA118100 and the Behavioral Measurement and Population Science shared resource.

Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Declarations

Ethics approval

The UNM Institutional Review Board approved all study procedures and materials, and all participants provided a written informed consent for participation in the study.

Consent to participate

The UNM Institutional Review Board approved all study procedures and materials, and all participants provided a written informed consent for participation in the study.

Conflict of interests

The authors declare no competing interests.