Awareness and Uptake of Direct-to-Consumer Genetic Testing Among Cancer Cases,Their Relatives,and Controls: The Northwest Cancer Genetics Network

Introduction

The translation of single nucleotide polymorphism (SNP) technology into commercial products such as direct-to-consumer (DTC) genetic testing is a controversial issue among members of the genetics and ethics communities. As the name suggests, DTC genetic tests are purchased by the consumer directly from the genetic testing company, without involving a health care provider either to order a test or to interpret the results. Often, these tests report risk for multifactorial diseases, such as cancer or diabetes, using data from SNP analysis and proprietary algorithms to calculate risk. The clinical validity and utility of these tests is questionable (Hunter et al., 2008; Eng and Sharp, 2010). There is concern that inappropriate interpretation of disease risk by the consumer could lead to physical and psychological harm and that many primary care providers are unprepared to discuss and interpret the results of DTC genetic tests (Hunter et al., 2008; McGuire and Burke, 2008; Powell et al., 2011).

The size of the DTC genetic testing market is difficult to estimate because most DTC genetic testing companies are not publicly held (Wright and Gregory-Jones, 2010). To assess this market, Goddard et al. (2006) conducted a representative survey in three states asking about awareness and use of DTC genetic tests. They found that 14% of the population were aware of DTC genetic tests, and less than 1% had used this type of test. Kolor et al. (2009) using the 2008 HealthStyles national survey, found similar prevalence of awareness (22%) and uptake (0.3%) of DTC genetic testing. Given that many of these tests are marketed and accessed online, one might expect that awareness and use of DTC genetic tests would be higher among social networkers. McGuire et al. (2009) found that Facebook users indeed reported higher awareness of DTC genetic testing than was found in national surveys, yet reported use was still fairly low (47% and 6%, respectively). Additionally, the Multiplex Initiative was conducted among a sample of members of the Henry Ford Health System in Detroit, Michigan (Kaphingst et al., 2010). Study participants were offered a multiplex genetic test—similar to those offered through DTC genetic testing companies—that tested for the risk alleles of 15 genetic markers previously associated with eight common chronic diseases. Only 11% of participants chose to receive multiplex testing. These studies indicate interest in and uptake of DTC genetic tests is low among the general population, but it is likely that interest and use will vary among different subgroups, particularly as awareness of the importance of family health history and genetic contributions to disease risk increases.

However, prior studies have not evaluated awareness, interest or use of DTC testing among different segments of the population, particularly among those individuals with cancer or their first-degree relatives. One recent study assessed interest in (but not awareness or use of) genetic testing for modest changes in breast cancer risk among women with a personal and/or family history of breast cancer, finding that three-quarters of these women were interested in testing (Graves et al., 2011). The DTC testing companies 23andMe and Navigenics offer testing for common variants associated with different types of cancer, including breast, colon, prostate, and melanoma (23andMe, 2011; Navigenics, 2011). Furthermore, 23andMe offers carrier testing for three specific BRCA1 and BRCA2 mutations found primarily among those of Ashkenazi Jewish descent (23andMe, 2011). Because of ease of access and the relatively low cost for DTC testing that frequently includes variants associated with cancers, we hypothesize that people with a personal or family history of cancer may be more aware, more interested, and have higher use of these tests than the general population.

Materials and Methods

The Northwest Cancer Genetics Network (NWCGN), funded by the National Cancer Institute (NCI), is a registry of individuals (subjects with cancer, their family members, and controls) who contributed information about individual and family history of cancer and other health conditions, tobacco use, and sociodemographic information (Anton-Culver et al., 2003). The purpose of the NWCGN is to collect and maintain data from a large group of participants to support collaborative investigations on the genetic basis of cancer susceptibility. It was one of the eight original sites contributing to the Cancer Genetics Network (CGN), established by the NCI in 1998 as a nationwide network of centers to specialize in the study of inherited predisposition to cancer. The site for the NWCGN is at the University of Washington.

For the parent NWCGN study, cases were recruited via population-based cancer registries and direct referral from health care providers throughout Western Washington. Controls were randomly selected, within the 5-year age and gender strata, from English-speaking male and female residents of the 3-county study area, and included individuals with cancer to allow for comparisons with a population-based control sample. Some participants self-referred to the registry in response to community awareness and education efforts and included both people with and without cancer. The NWCGN also enrolled first-degree relatives of cases and those who self-referred to the registry. All participants completed core data questionnaires at baseline and have been sent follow-up questionnaires since study entry. The questionnaires cover a variety of topics, including basic demographic information, personal medical history, family medical history, and awareness and use of genetic testing. The NWCGN is the only CGN site to ask questions about DTC genetic tests, and it served as the source of subjects for this study.

From 2008 to 2009, all active NWCGN participants (n=3719) were mailed a follow-up survey that included questions about awareness, intention, and actual use of DTC genetic tests (Table 1). These questions, derived from state-added questions on Michigan's Behavioral Risk Factor Surveillance System survey in 2009, were pilot-tested by the Michigan Department of Community Health.

Individuals who responded to any of these questions were considered eligible for the present study. Participants who responded “yes” to Question 3 and/or “already had genetic testing” to Question 5 were considered to have had DTC genetic testing. Interest in genetic testing was defined as answering “considering having genetic testing,” “probably will have genetic testing,” or “definitely will have genetic testing” to Question 5.

For the present study of DTC genetic testing, participants were categorized into four groups based on their referral method and cancer status. Those categorized as “Cases” were recruited through a health professional or a cancer registry and had cancer at the time they were recruited to the NWCGN study. The most frequent cancers reported at the NWCGN study baseline were melanoma (34%), thyroid (16%), breast (12%), skin (12%), and prostate (9%). “Relatives” were the first-degree family members of those identified as having had cancer at recruitment, but who themselves had not had cancer at the time they were recruited to the NWCGN study. The “Controls” category was made up of study participants who had not had cancer at the time of recruitment to the NWCGN and were not a first-degree relative of a case. Although the parent study included people with cancer at baseline among the population-based controls, in the present study, we excluded people who had a personal history of cancer at recruitment from the “Control” category to clarify interpretation of results. Finally, the “Self-referral” category was composed of both individuals with and without cancer at recruitment (39% and 61%, respectively). Because those who self-referred to the NWCGN may be more interested in genetics than those who were actively recruited, we chose to keep “Self-referral” as a separate category rather than incorporate these participants into “Cases” and “Controls.”

Family history of cancer was assessed as the number of cancer cases reported normalized by the number of family members reported. This ratio was then categorized into four groups based on the percent of family members reported to have had cancer, where the highest category was individuals reporting cancer in 25% or more of relatives (roughly the highest quartile) and the lowest category was individuals who reported no family history of cancer.

This study was approved by the University of Washington Human Subjects Division, and all subjects provided informed consent to participate.

Means and proportions were calculated for continuous and categorical variables, respectively. Analysis of variance was used to compare means, and the chi-squared test was used to compare categorical variables across categories of participant type. Logistic regression analysis was used to calculate odds ratios (OR). All analyses were conducted using the STATA 8 statistical software package.

Results

A total of 1267 participants in the NWCGN responded to the survey (34% response rate). The average age of respondents was 62.4 years. Sixty-four percent of respondents were women. Most respondents had at least some college education; only 14% reported attaining a high school diploma or less (Table 2). Forty-nine percent of respondents reported awareness of DTC genetic tests. Of those, 19% reported interest in using a DTC genetic test and 0.9% reported having used a DTC genetic test. There were significant differences in awareness, interest, and use of DTC genetic tests by participant type (Table 3). Additionally, those who self-referred to the NWCGN were five times more likely to report a family history of cancer compared to controls (OR: 5.45 [2.46-12.05], p<0.001). Cases were not more likely to report a family history of cancer compared to controls (p=0.15).

Discussion

Awareness of DTC genetic testing was higher among this highly educated sample of individuals with cancer, their relatives, controls, and self-referrals compared to awareness in national studies (49% vs. 14% or 22%) (Goddard et al., 2006; Kolor et al., 2009). Whether they had a history of cancer or not, those who self-referred into the NWCGN study were more aware of DTC testing than were other participant types. This finding suggests that those who are highly motivated and interested in research are also aware of DTC genetic testing. NWCGN participants recruited as cancer cases were also more aware of DTC genetic testing compared to controls. Additionally, participants with the strongest family histories of cancer were more aware of DTC genetic testing compared to those without a family history of cancer, even after adjusting for participant type. Higher educational attainment was also associated with awareness of DTC genetic testing, echoing findings of the Multiplex Initiative (Kaphingst et al., 2010).

Although awareness of DTC genetic testing was higher in the NWCGN compared to other studies, in contrast to Graves and colleagues' study of women at high risk for breast cancer in which 77% expressed definite interest in genetic testing for modest changes in breast cancer risk, only 19% of NWCGN participants who were aware of DTC genetic testing were also interested in obtaining testing (Graves et al., 2011). The interest in testing in the NWCGN sample is similar to the findings from the Multiplex Initiative, in which 11% of study participants ultimately decided to undergo multiplex genetic testing (Kaphingst et al., 2010). Additionally, although study participants who were recruited as cancer cases and participants who self-referred to the study were more aware of DTC genetic testing, neither they nor relatives of the cancer cases were more interested in obtaining testing compared to controls. However, having a family history of cancer in 25% or more of relatives was strongly associated with interest in DTC genetic testing. These findings suggest that having a family history per se does not drive interest in DTC genetic testing, but rather the strength of the family history motivates DTC genetic testing interest.

Less than 1% of our study sample reported having had a DTC genetic test, which is very similar to findings from national surveys (Goddard et al., 2006; Kolor et al., 2009). However, over half of these participants gave discordant answers to questions assessing DTC use. These participants also reported hearing about DTC testing through their health care provider (instead of through a DTC medium) and gave specifics about the kind of test they received that are characteristic of clinical genetic tests rather than DTC tests. Taken together, this evidence suggests that these participants were confused about what DTC genetic testing is and likely did not engage in DTC testing. If this is true, our DTC use prevalence estimate is inflated by about 50%; the prevalence of DTC awareness and interest are also likely overestimated. Furthermore, DTC use, interest, and awareness prevalence estimates assessed by population-based surveys may be similarly overestimated, due to a possible conflation of DTC and clinical genetic testing in the general population.

Demographically, our sample is highly educated, which limits the generalization of our results, even to other individuals with cancer and their relatives. Further, all data were self-reported, thus our data could be affected by recall bias.

Further studies are needed to assess the prevalence of DTC genetic testing awareness, interest, and use in DTC testing among individuals with a positive family history of disease. Additionally, our finding that more than half of our participants who reported DTC genetic testing appeared to confuse DTC testing with traditional clinical genetic testing points to a need for additional clarification of true testing modality on future surveys assessing DTC awareness, interest, and use. Additional questions on the health care provider's involvement in testing and specimen tested (i.e., blood versus buccal swab), for example, may help elucidate whether a participant reporting DTC testing likely received testing through this modality.