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Original Research |

Genetic and Environmental Risk Assessment and Colorectal Cancer Screening in an Average-Risk Population: A Randomized TrialRisk Assessment and Colorectal Cancer Screening

David S. Weinberg, MD, MSc; Ronald E. Myers, PhD; Eileen Keenan, MA; Karen Ruth, MS; Randa Sifri, MD; Barry Ziring, MD; Eric Ross, ScM, PhD; and Sharon L. Manne, PhD
[+] Article, Author, and Disclosure Information

From Fox Chase Cancer Center and Jefferson Medical College, Philadelphia, Pennsylvania, and Cancer Institute of New Jersey, New Brunswick, New Jersey.

Acknowledgment: The authors thank James Cocroft, Anett Petrich, Heidi Kelly, Thomas Wolf, and the members of the Fox Chase Cancer Center Cancer Genomics Facility.

Grant Support: By grants R01CA112230 (Dr. Weinberg) and P30 CA006927 from the National Institutes of Health.

Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M14-0765.

Reproducible Research Statement:Study protocol: Available from Dr. Weinberg (e-mail, d_weinberg@fccc.edu). Statistical code and data set: Available from Dr. Ross (e-mail, eric.ross@fccc.edu).

Requests for Single Reprints: David S. Weinberg, MD, MSc, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111; e-mail, d_weinberg@fccc.edu.

Current Author Addresses: Drs. Weinberg and Ross, Ms. Keenan, and Ms. Ruth: Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111.

Dr. Myers: Department of Medical Oncology, Division of Population Science, Thomas Jefferson University, 834 Chestnut Street, Suite 314, Philadelphia, PA 19107.

Dr. Sifri: Department of Family and Community Medicine, Thomas Jefferson University, 1015 Walnut Street, Suite 401, Philadelphia, PA 19107.

Dr. Ziring: Department of Internal Medicine, Thomas Jefferson University, 833 Chestnut Street, Suite 701, Philadelphia, PA 19107.

Dr. Manne: 10 Park Avenue, Apartment 16JH, New York, NY 10016.

Author Contributions: Conception and design: D.S. Weinberg, R.E. Myers, R. Sifri, E. Ross, S.L. Manne.

Analysis and interpretation of the data: D.S. Weinberg, R.E. Myers, K. Ruth, R. Sifri, E. Ross, S.L. Manne.

Drafting of the article: D.S. Weinberg, R.E. Myers, K. Ruth, R. Sifri, B. Ziring, E. Ross, S.L. Manne.

Critical revision of the article for important intellectual content: D.S. Weinberg, R.E. Myers, R. Sifri, S.L. Manne.

Final approval of the article: D.S. Weinberg, R.E. Myers, K. Ruth, R. Sifri, B. Ziring, E. Ross, S.L. Manne.

Provision of study materials or patients: R.E. Myers, R. Sifri, B. Ziring.

Statistical expertise: K. Ruth, E. Ross.

Obtaining of funding: D.S. Weinberg, E. Ross, S.L. Manne.

Administrative, technical, or logistic support: D.S. Weinberg, R.E. Myers, E. Keenan, R. Sifri, B. Ziring, E. Ross.

Collection and assembly of data: D.S. Weinberg, R.E. Myers, E. Keenan, R. Sifri.

Ann Intern Med. 2014;161(8):537-545. doi:10.7326/M14-0765
Text Size: A A A

Background: New methods are needed to improve health behaviors, such as adherence to colorectal cancer (CRC) screening. Personalized genetic information to guide medical decisions is increasingly available. Whether such information motivates behavioral change is unknown.

Objective: To determine whether individualized genetic and environmental risk assessment (GERA) of CRC susceptibility improves adherence to screening in average-risk persons.

Design: 2-group, randomized, controlled trial. (ClinicalTrials.gov: NCT0087360)

Setting: 4 medical school–affiliated primary care practices.

Participants: 783 participants at average risk for CRC who were not adherent to screening at study entry.

Intervention: Participants were randomly assigned to usual care or GERA, which evaluated methylenetetrahydrofolate reductase polymorphisms and serum folate levels. On the basis of prespecified combinations of polymorphisms and serum folate levels, GERA recipients were told that they were at elevated or average risk for CRC.

Measurements: The primary outcome was CRC screening within 6 months of study entry.

Results: Overall screening rates for CRC did not statistically significant differ between the usual care (35.7%) and GERA (33.1%) groups. After adjustment for baseline participant factors, the odds ratio for screening completion for GERA versus usual care was 0.88 (95% CI, 0.64 to 1.22). Within the GERA group, screening rates did not significantly differ between average-risk (38.1%) and elevated-risk (26.9%) participants. Odds ratios for elevated- versus average-risk participants remained nonsignificant after adjustment for covariates (odds ratio, 0.75 [CI, 0.39 to 1.42]).

Limitation: Only 1 personalized genetic and environmental interaction and 1 health behavior (CRC screening) were assessed.

Conclusion: In average-risk persons, CRC screening uptake was not positively associated with feedback from a single personalized GERA. Additional studies will be required to evaluate whether other approaches to providing GERA affect screening utilization differently. These findings raise concern about the effectiveness of moderately predictive assessment of genetic risk to promote favorable health care behavior.

Primary Funding Source: National Institutes of Health.


Grahic Jump Location

Study flow diagram.

CRC = colorectal cancer; GERA = genetic and environmental risk assessment.

Grahic Jump Location




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Risk Assessment and Colorectal Cancer Screening
Posted on October 29, 2014
Thomas F. Imperiale, MD
Indiana University Medical Center, Regenstrief Institute, and Roudebush VA Medical Center
Conflict of Interest: None Declared
While the study by Weinberg and colleagues is interesting and well-done, the negative results are not surprising. Among several possibilities are the timeframe for estimating risk for colorectal cancer (CRC), magnitude of the risk, the 6-month interval for assessing screening uptake, and whether the genetic and environmental risk assessment (GERA) had meaning to study subjects.

With regard to the timeframe for CRC risk, it appears that study subjects were told about their lifetime risk for CRC. It may be that knowing about lifetime CRC risk has less of a motivating effect on people / patients, particularly in the short-term (6 months, perhaps a year) than knowing about a current or near-term risk. In general, people want to know whether and what they need to do now or in the near term in response to learning about “risk”. Since CRC prevalence is so low, and since advanced precancerous polyps have become the target lesion of screening, telling people about their current risk of advanced neoplasia (that is, the combination of CRC and advanced polyps) could result in screening uptake sooner rather than later, and sooner than would knowing lifetime CRC risk (which is understood to be a future risk).

The perception of a low magnitude of risk may be another reason for inaction in the short-term. Average lifetime risk for CRC about 5% (or 1 in 20). Even if GERA suggests a doubling of lifetime risk, that risk is still just 11%, which many would interpret as having a nearly 90% chance of not getting CRC, supporting inertia to avoid the screening issue, especially in the short-term. In contrast, telling people that they have a 20-25% chance (1 in 4 or 1 in 5 chance) of having an advanced, precancerous polyp present “now” (because of several phenotypic features) may be a greater motivator to get screened in the short-term. Given a future risk for CRC – whether elevated or not - allowing just 6 months to assess screening uptake likely contributed to the negative results.

Finally, whether people understand and accept GERA results may be questioned. People can probably understand and relate better to older age, male sex, cigarette smoking, a family history of CRC, overweight, and other phenotypic features as risk factors than they can to polymorphic variants of methylenetetrahydrofolate reductase and low serum folate levels as increasing risk for CRC and thus, as motivators toward CRC screening.
Genetic Counselors and the Future of Risk Assessment
Posted on November 21, 2014
Sara Pirzadeh-Miller, Victoria Raymond, Sara Knapke
National Society of Genetic Counselors, Cancer Special Interest Group
Conflict of Interest: None Declared
Weinberg and colleagues (1) recently published manuscript highlights the complexities of using genetic polymorphisms and their associated cancer risk to encourage lifestyle modifications. The study attempts to consider risks, benefits and potential barriers to personalized medicine and associated patient/provider uptake. The authors discuss their rationale for utilizing trained nurses in lieu of genetic counselors, stating the number of genetic counselors seems inadequate to meet health service needs even in high-risk settings, citing a reference from 1990 (2) which does not reflect current data.

Currently, there are more than 4,000 certified genetic counselors (CGCs) in the United States, all of whom are trained to provide a cancer genetics consult and approximately 30% of whom report cancer genetics as their primary specialty (3). There has been a 75% increase in the CGC workforce since 2006. Annual growth in the profession is trending upwards of 7-10 percent; this partially reflects the growth in the number and capacity of training programs as we prepare for future needs. Recently, genetic counselors were cited in the “Top 10 Fastest Growing Careers.” According to the Bureau of Labor Statistics, the genetic counseling profession is predicted to grow 41% by the end of 2022; a rate much faster than other health care professions (4-5).

Access to CGCs is excellent. Approximately half of respondents to the National Society of Genetic Counselors (NSGC)’s 2014 Professional Status Survey report availability for a new patient consultation within one week (3). Alternative genetic service modalities, including video or telephone genetic counseling, increase access to patients in underserved areas. A directory of genetic counselors is available at www.nsgc.org .

The authors state that ‘a lack of familiarity with genomics on the part of patients (and providers) has been cited as a concern limiting the effect of genetic testing’. This ‘lack of familiarity’, and the mounting complexity of genetic and genomic testing, highlights the importance of collaboration between genetics/genomics and medical specialties. NSGC welcomes opportunities to partner with healthcare organizations to provide genetics/genomics education. Genetic counselors are essential members of the healthcare team and work with our physician partners to provide counseling, enhance overall patient care, accelerate educational opportunities for clinicians, and facilitate appropriate utilization of genetic services and testing to ensure sound medical management and decision making. NSGC suggests that healthcare organizations and providers unfamiliar with genetic services work with genetic counselors to ensure delivery of high quality genetic services to patients.

(1) Weinberg DS, Myers RE, Kennan E, Ruth K, Sifri R, Ziring B, Ross E, and Manne SL. Genetic and Environmental Risk Assessment and Colorectal Cancer Screening in an Average Risk Population. Annals of Internal Medicine 2014; 161(8):537-45.
(2) Wilfond BS, Fost N. The cystic fibrosis gene: medical and social implications for heterozygote detection. JAMA 1990;263:2777-83.
(3) NSGC Professional Status Survey 2014
(4) http://www.usnews.com/education/best-graduate-schools/articles/2014/03/19/study-a-hot-concentration-today-for-a-future-health-care-job
(5) http://jobs.aol.com/articles/2014/11/10/six-figure-jobs-genetic-counselors-earn-up-to-250k/
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