Referral of Patients with Suspected Hereditary Breast-Ovarian Cancer or Lynch Syndrome for Genetic Services: A Systematic Review

Yen Y Tan^1,2,3* Leonie L Noon^1,5 Julie M McGaughran^1,4 Andreas Obermair^1,2 Amanda B Spurdle³

¹School of Medicine, The University of Queensland, Australia

²Queensland Centre for Gynaecological Cancer Research, Australia

³Genetics and Computational Biology Division, Queensland Institute of Medical Research, Australia

⁴Genetic Health Queensland, Australia

⁵Department of Medicine, Familial Cancer Service, Westmead Hospital, Australia

*Corresponding Author:

Yen Y Tan
Rm 727, Level 7 Block 6
Royal Brisbane & Women’s Hospital
Herston, QLD 4029, Australia
Tel: (07) 3346 5192
E-mail: y.tan@uq.edu.au

Received date: November 14, 2013; Accepted date: December 18, 2013; Published date: December 20, 2013

Citation: Tan YY, Noon LL, McGaughran JM, Spurdle AB, Obermair A (2013) Referral of Patients with Suspected Hereditary Breast-Ovarian Cancer or Lynch Syndrome for Genetic Services: A Systematic Review. J Community Med Health Educ 3:255. doi: 10.4172/2161-0711.1000255

Copyright: © 2013 Tan YY, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Visit for more related articles at Journal of Community Medicine & Health Education

Abstract

Background: Referral of individuals with suspected hereditary breast-ovarian cancer or Lynch syndrome for genetic services is very important as it allows effective surveillance and prevention strategies for these individuals and their family members. However, evidence to date indicates poor recognition of both hereditary cancer syndromes, and inappropriate or under referral of patients with suspected hereditary cancer syndromes for genetic services. In this review, we summarize the most common physician-related factors important for referral of these patients for genetic services. Methods: A systematic search was conducted in both PubMed and Embase for studies published from the earliest date possible until May 1, 2013. The search terms included MeSH and Emtree headings, and free-text words: “health knowledge, attitudes, practice”, “attitude of health personnel”, “clinical competence”, “family history”, “referral and consultation”, “health care availability”, “availability of health care”, “health care access”, “accessibility of health care”, “genetic services”, “genetic counseling”, “genetic testing”, “genetic predisposition to cancer”, “hereditary neoplastic syndromes”, “familial cancer”, “hereditary cancer”, “Lynch syndrome”, “hereditary breast and ovarian cancer syndrome”, and “physicians”. Three reviewers abstracted data and assessed quality independently, with disagreement resolved by consensus. Results: The search revealed 202 discrete citations. One hundred and twelve articles were retrieved and 41 relevant citations were assessed. Of the 41 relevant studies, 18 assessed family history documentation, 29 assessed physicians’ knowledge, 19 assessed awareness of genetic services, 29 assessed physicians’ referral patterns, and only three investigated physicians’ ability to distinguish between low- and high-risk patients. Physicians demonstrated insufficient knowledge about hereditary cancer syndromes, particularly Lynch syndrome. Family history documentation was inadequate and lacked details for proper risk assessment, and physicians were more likely to refer patients directly to a genetic service when they were aware of such services. Conclusions: This review highlights the need to improve referral of high-risk individuals and their family members for genetic services.

Keywords

Breast ovarian cancer; Genetic services; Family history; Hereditary cancer; Health care Delivery; Knowledge, Attitudes and referral practices

Introduction

Hereditary breast-ovarian cancer syndrome and Lynch syndrome (also known as hereditary non-polyposis colorectal cancer, HNPCC) are the most common autosomal dominantly inherited cancer syndromes. The syndromes are accountable for about 5-10% of all cancers, and are characterized by early onset and multiple cancers in the family [1]. While individuals carrying germline mutations in the breast cancer genes (BRCA1 or BRCA2) have a 40 to 87% lifetime risk of developing breast cancer and up to 40% lifetime risk of developing ovarian cancer,1 individuals with mismatch repair gene mutations have increased lifetime risk of up to 70% for developing colorectal or endometrial cancers [2]. Depending on the type of gene affected, mutation carriers also have increased risks of other cancers such as pancreas, prostate, melanoma, stomach, small intestine, ureter and kidney [1].

Detailed clinical data such as age, family history and clinicopathologic characteristics are important for identifying individuals at greatly increased risk of developing cancer due to cancer gene mutation. These individuals and their family members can then be offered accurate cancer risk assessment, genetic counseling and/ or genetic testing, and appropriate cancer screening and prevention options. Regular colonoscopy and risk-reducing hyserecttomy and bilateral salpingo-oophorectomy have been proven to be effective for the prevention of colorectal, endometrial and ovarian cancer [3-6], as are tamoxifen and risk-reducing mastectomy for the prevention of breast cancer [7]. However, evidence to date indicates poor recognition of hereditary breast-ovarian cancer and Lynch syndrome [8,9], and inappropriate or under referral of patients for genetic services (i.e. genetic counseling and/or testing) [9-13].

In recent years, two reviews assessed physicians’ barriers to the delivery of genetic services [14,15], and the most consistent findings were a general lack of basic knowledge about genetics and lack of confidence among physicians to provide genetic services. Collection and documentation of family history among physicians were also reported to be suboptimal, as is interpretation of family history information [16]. Other reported barriers include but are not limited to lack of genetic skills, lack of awareness of genetic services among physicians, and logistical and financial barriers for patients [15]. No reviews to date have investigated how physicians’ documentation of family history, their knowledge about hereditary cancer syndromes, and their awareness of genetic services would influence referral of individuals, specifically individuals with suspected hereditary breastovarian cancer or Lynch syndrome, for genetic services. Therefore, the aim of this systematic review was to summarize findings regarding the referral patterns of patients with suspected hereditary breast-ovarian cancer or Lynch syndrome for genetic services, and the following key questions: (i) Is family history of cancer documented adequately during patient consultation? (ii) Do physicians have sufficient knowledge to identify individuals with suspected hereditary breast-ovarian cancer or Lynch syndrome? (iii) Do physicians know how or where to access genetic services? For the purpose of this paper, referral for genetic services is defined as referral of patients from non-genetic healthcare providers (e.g. general practitioners and non-genetic specialists) to genetic specialists (e.g. genetic counselors, medical geneticists, genetic nurses).

Methods

A systematic search was conducted in both PubMed and Embase for studies published from the earliest date possible until May 1, 2013. Searches were conducted independently by two reviewers (YT and LN) and a professional librarian using the following MeSH terms, Emtree headings, and free-text words: “health knowledge, attitudes, practice”, “attitude of health personnel”, “clinical competence”, “family history”, “referral and consultation”, “health care availability”, “availability of health care”, “health care access”, “accessibility of health care”, “genetic services”, “genetic counseling”, “genetic testing”, “genetic predisposition to cancer”, “hereditary neoplastic syndromes”, “familial cancer”, “hereditary cancer”, “Lynch syndrome”, “hereditary breast and ovarian cancer syndrome”, and “physicians”.

Study selection

Studies were considered eligible if they: (i) were a chart review, observational, cohort, cross-sectional, mixed-method or qualitative studies which were peer-reviewed and published in the English language, (ii) investigated physicians’ ability to identify hereditary breast-ovarian cancer or Lynch syndrome via direct (e.g. measures of knowledge) or indirect (e.g. confidence, satisfaction or comfort level) methods, (iii) assessed physicians’ documentation of family history of cancer during patient consultation, (iv) assessed physicians’ awareness of access to clinical genetic services, and (v) recorded referral of patients for cancer genetic services.

Studies were excluded if they (i) were conference abstracts, intervention study, review articles, essay, supplementary, commentary, or editorial pieces, and (ii) investigated views of patients or nonphysician practitioners.

Data extraction, synthesis and validation

Data extraction and quality assessment were undertaken by one reviewer and checked independently by a second reviewer. Studies were reviewed initially on the basis of title and abstracts, and then all fulltext manuscripts that appeared relevant were retrieved and assessed for eligibility. Additional studies were identified by a citation search of all eligible papers, and of relevant published reviews.

Each selected study was mapped to the research questions and the following information was extracted: last author’s name, year of publication and country in which the study was performed, study design, participants’ characteristics, response rates and our outcome measures of interest. Our outcome measures include (i) physicians’ ability to identify hereditary breast-ovarian cancer or Lynch syndrome, (ii) physicians’ documentation of family history of cancer during patient consultation, (iii) accessibility to clinical genetics services, and (iv) the referral patterns for cancer genetic services.

The results were tabulated and crosschecked for discrepancies. Differences in opinion between the two reviewers were resolved by consensus.

Statistical analysis

Frequencies and percentages of data and key findings are described within the table of evidence. Given the lack of study homogeneity, subjects, statistical methods, research questions and outcomes, a metaanalysis to generate a pooled estimate was not performed.

Results

Figure 1 shows the process of study selection. Initial searching and reference mining yielded 202 discrete citations. Nineteen duplicate citations were removed. Following the first screening, 71 citations were excluded and 112 potentially relevant citations were retrieved for further review. Using the inclusion and exclusion criteria, 70 publications were excluded. Initial disagreement over the selection of six publications occurred. Following discussions, two publications were included, with the remaining four publications referred to a third reviewer for arbitration. In total, 41 publications were selected for the review. Of the 41 relevant publications, 18 assessed family history documentation, 29 assessed physicians’ knowledge, 19 assessed awareness of genetic services, and 29 assessed physicians’ referral patterns. Only three studies assessed physicians’ ability to distinguish between low- and high-risk patients.

Figure 1: Selection of studies for review.

Study characteristics

The main characteristics of the study populations and outcome measures are detailed in Table 1. The majority of the studies included were cross-sectional (n=34), followed by chart reviews (n=3), mixedmethod (n=2), qualitative (n=1) and observational (n=1). Of the 34 cross-sectional studies, 24 studies originated from North America, 8 studies originated from Europe, 1 study from Turkey and 1 study from New Zealand. Other non-cross-sectional studies originated either from North America (n=6) or the UK (n=1). Of all the studies selected, 10 studies investigated hereditary breast-ovarian cancer, 7 studies investigated Lynch syndrome, 7 studies investigated both hereditary breast-ovarian cancer and hereditary colorectal cancer, and the remaining 17 investigated hereditary cancers in general. Overall, there were 29 studies examined physicians’ referral patterns.

Table 1: Table of evidence of reviewed studies

Lack of detail and accuracy in family history of cancer documented by physicians

Eighteen studies covered this topic, including 13 cross-sectional studies [17-24], 3 chart reviews [8,25,26], 1 mixed-method study [27] and 1 observational study [28]. In general, physicians identify family history of cancer as the primary reason for referring a patient for genetic risk assessment. Despite the recognition, family history information tends to be under-collected in clinical practice [18,29,30]. Consistent with previous reviews and studies, only a small proportion of physicians frequently ask patients for the age and type of cancer diagnosed in the affected relative(s) when a family history of cancer is noted [8,18,20,25-28]. Family history information collected was also less accurate when the complexity of family history documentation increases with the number of cancers in the family [26].

Several other studies reported physicians’ lack of skill and confidence in constructing a three-generation pedigree or estimating risk by pedigree analysis [31-33]. Physicians who were confident were three times more likely to collect family history information using a three-generation pedigree for risk assessment [34].

Lack of time was also considered a barrier for comprehensive family history collection [15,23,35]. In an observational study of 138 primary care physicians in the United States, Acheson and colleagues found that physicians spent less than 2.5 minutes on discussing family history with patients, and that discussion took place more often during preventive care consultations rather than visits due to illness [36].

Poor identification of hereditary cancer, particularly Lynch syndrome

Twenty-nine studies investigated the identification of hereditary cancer, including 24 cross-sectional studies [9,18-21,31-34,36-51] 2 chart reviews [25,26], 1 observational study [28], 1 mixed method [27], and 1 qualitative study [52]. Overall, physicians demonstrated insufficient knowledge of hereditary breast-ovarian cancer and Lynch syndrome. Physicians lack knowledge about inheritance [21,32,38,42,45-47,50,51] and were less able to discriminate between low and high-risk patients [9,28,31,38,39]. Their competence in distinguishing hereditary breast-ovarian cancer and Lynch syndrome was dependent upon their specialty [34,42,43,46]. General practitioners and gynecologists were reported to be more competent in identifying hereditary breast-ovarian cancer patients than Lynch syndrome patients [31-34,42,43]. Consistent with the historical understanding that colorectal cancer is the hallmark cancer associated with Lynch syndrome, gastroenterologists were the most competent in identifying individuals with a family history consistent with hereditary colorectal cancer for genetic services compared to other physicians [19,41,42]. Findings from a single study from Sweden further suggest that physicians were unfamiliar with various Lynch-associated cancer risks, with more than half of the physicians underestimating the risk of colorectal and endometrial cancers [40].

Physicians’ knowledge of hereditary breast-ovarian cancer and Lynch syndromes were indirectly assessed by exploring their satisfaction, confidence and comfort level in identifying patients for genetic referral [9,18,33,37,41,48,49]. Physicians with greater knowledge of hereditary breast-ovarian cancer and Lynch syndromes had higher levels of confidence and were therefore more comfortable with identifying patients for referral [34,41].

Low awareness of local genetic providers leads to low access of genetic services

Nineteen cross-sectional studies [18,20-22,24-29,30,32,34,36,39,41,42,44,45,49,53-55] and two mixed-method studies [27,56] were identified for this topic. Several studies have shown that physicians were more likely to refer a patient directly to a clinical genetics service when they were aware of such service [20,24,29,44], and if such service was available at close proximity [17,20,30,41], Unfortunately, our review shows that many physicians did not know or knew very little about the availability of their local genetic centre and the services it provided [18,20,24,27,30,32,41,45,54,55]. Physicians were also less aware of the availability of genetic testing for Lynch syndrome compared to hereditary breast-ovarian cancer or familial adenomatous polyposis [18,21,41,42].

Access to a clinical genetics service, such as obtaining an appointment for consultation with a geneticist was considered to be a challenge by primary care physicians, especially for those practicing in suburban and rural areas [34,36]. The lack of face-to-face genetic consultation and distance (such as travelling by car for more than two hours) to a genetic consultant, were indicated by rural and suburban physicians as challenges for making referrals [34,36,44]. Long waiting time for a genetic consultation was also a concern for urban, suburban and rural physicians in the United States and New Zealand [17,24,29,34,44].

While cost of genetic services was a concern for most North American physicians when referring patients [17,21,24,53-56], the concern was less often reported by physicians practicing outside the United States [44,57]. Although the cost of testing was considered a barrier to some extent by some physicians in Australia, they were more concerned about the lack of reimbursement by health insurance [57].

Referral patterns

Of the 41 studies reviewed, 29 studies examined physicians’ referral patterns. There was a high heterogeneity among studies of the referral factors investigated, but the most prominent factors were specialty, gender and years in practice since graduation. Specialists in general were more adept at referring patients for genetic services [17,41,43,56], as were female practitioners and recent graduates [34,41,48,50]. Other factors reported include physicians’ concern for patient’s family members, and to enhance risk assessment and medical management for patients [18,29]. Physicians with positive attitudes toward genetic services had more confidence in their knowledge about cancer genetics and the referral criteria; those who were more skilled in pedigree analysis and cancer risk assessment were also more likely to identify patients for referral [17,34,41]. Nevertheless, the chart reviews showed poor identification of patients appropriate for genetic referral [8,25,26].

Referral of patients with suspected hereditary breast-ovarian cancer or Lynch syndrome was low in general. Physicians were more likely to refer a patient for genetic services when the patient initiated the discussion of family history, and requested for a referral [9,17,18,20,24,27,29,30,37,50]. Additionally, referral of patients for genetic testing varied depending on the type of cancer diagnosed in the family [18,27,43].

Discussion

This is the first systematic review to exclusively focus on referral of patients with suspected hereditary breast-ovarian cancer or Lynch syndrome. Overall, our review highlights the need to improve cancer genetics education and family history documentation among health care providers, and increase awareness of genetic services. As most of the studies included in this review were of cross-sectional design and were North American origin, it is likely that the results from this review are more generalizable for clinical practice in North America. The current study also found ‘referral for genetic services’ was infrequently measured as an outcome variable. The lack of measures of association between referral and the potential barriers studied makes it difficult to compare the effects of the barriers on providers’ decisions to refer between studies. In addition, some studies reporting to assess barriers to ‘referral for genetic services’ did not measure the key component genetic counseling, but only focused on genetic testing aspects (‘use of genetic services’).

The current study focused on the hereditary cancer syndromes more commonly encountered in the clinical genetics setting (hereditary breast-ovarian cancer and Lynch syndrome), found physicians lack sufficient knowledge about genetics and lack of confidence in interpreting familial patterns of disease. These findings are similar to a recent broad literature review on the delivery of genetic services for common chronic adult diseases [14,15], but our detailed investigation highlights the scarcity of research investigating referral of women with suspected Lynch syndrome who may be at increased risk for developing endometrial cancer, or colorectal cancer after endometrial cancer [58,59]. Despite the growing recognition that women with mismatch repair gene mutations have equal if not higher risk of developing endometrial cancer than colorectal cancer [59,60], physicians underestimated the risk of Lynch-associated endometrial cancer and other extracolonic cancers [40]. Reduced awareness of Lynchassociated cancers may consequently lead to reduced identification and patient referral. Hence, increased efforts to educate physicians about both Lynch-associated extracolonic cancers, and other hereditary cancer syndromes, may increase physicians’ knowledge and confidence, thereby increasing patient referrals and improving patient outcomes. There is also a paucity of research on the ability of physicians in care of women (e.g. gynecologists) to identify and subsequently refer possible mismatch repair gene mutation carriers for genetic services, as well as studies to compare the genetic counseling provided by non-genetic specialists versus genetic specialists to improve patient outcomes. Further controlled studies are required to provide evidence-base in these areas.

Although family history is a relatively simple clinically relevant tool for targeted screening and interventions for individuals at increased risk of cancer, our review shows that family history documentation is underutilized in clinical practice. Consistent with findings from previous reviews, physicians’ family history documentation was inadequate, and when recorded often lacks details and completeness [61,62]. Since time constraints and lack of genetic knowledge were cited as barriers to collect family history, [27,35,44] a computerized family history system could be implemented in the clinical setting to aid family history collection [63]. Such systems have demonstrated to be effective and convenient in collecting family history information in a clinical setting, and have been recently implemented at two primary care clinics [63]. Where relevant, results from tumor testing in combination with family history should be used to improve identification and referral of patients with suspected hereditary cancer syndromes [64-66]. Future possibilities would be to incorporate built-in decision support software to prompt physicians when a genetic referral is warranted. However, decision tools are complex interventions [67], and development of such tools should take into account possible variation in service type across different jurisdictions, and should consider whether the evidence base identified is relevant to their own setting.

Physicians limited knowledge of genetic services might reflect physicians’ infrequent use of genetic services due to infrequent contact with patients with hereditary cancer syndromes and other inherited conditions [44]. In the hospital setting, multidisciplinary teams consisting of genetic and non-genetic health professionals have been proposed, or are in place, to address the changing landscape of genetic health care [68], although the effectiveness of multidisciplinary team meetings in improving patient outcomes is not yet proven. The roles assigned for each specialist and the various types of liaison planned may forge new relationships and promote discussion between non-genetic and genetic professionals regarding treatment and management options for high-risk patients [68]. Such multidisciplinary team meetings may facilitate and simplify a referral process, and reduce waiting times for patients who are eligible for genetic consultation and/or testing. It may be necessary to have a coordinator with an appropriate genetic background to act as contact point for physicians, and patients, and to manage eligible patients through the various phases of care that may span different centers. However, implementation of multidisciplinary teams in cancer services can be difficult as health services vary across jurisdictions; randomized trials should be considered to investigate the feasibility and effectiveness of such multidisciplinary meetings. Implementation of a multidisciplinary meeting may be even more difficult to establish in rural areas due to lack of health professionals and available specialist cancer or genetic services, and might be a challenge due to time constraints. Although further development of telehealth would assist this [36], there would be challenges coordinating such a system given clinical genetics services in some areas serve an entire state. Moreover, high-risk individuals may seek advice or be identified in the general practice or specialist care setting, which would not be captured by hospital-based multidisciplinary meetings. Clear referral guidelines for both hospital and other clinical settings would thus assist in providing relevant information for triage of patients with suspected hereditary cancer to genetic specialists for genetic consultation and risk-appropriate care [55,69,70].

There are some limitations to this study. While other care models for genetic services that do not involve referral to genetic specialists exist, we did not assess these under the assumption that, as for other specialist services provided to cancer patients, genetic specialists is likely to provide the most optimal and comprehensive care for patients with suspected hereditary cancer. In addition, vast majority of studies included in this review were of cross-sectional design; it would be beneficial to conduct interventional studies to better assess referral based on physician knowledge and skills relating to factors important for referral of patients for cancer genetic services.

Conclusion

This review highlights the need for research into improving referral of high-risk individuals and their family members for genetic services. More educational efforts are needed for hereditary cancers, particularly for Lynch syndrome. Clear referral guidelines and integration of a computerized family history tool with a built-in decision support to prompt physicians when a referral is warranted may improve referral of possible mutation carriers for genetic services. Increased collaboration among general practitioners, specialists and medical genetic specialists may also improve referral and clinical management of at-risk patients, and their family members, who would ultimately benefit from a genetic consultation or testing.

Acknowledgements

Authors would like to thank Lars Eriksson, health sciences librarian, for his assistance with the literature search.

References

1. Garber JE, Offit K (2005) Hereditary cancer predisposition syndromes. J Clin Oncol 23: 276-292.
2. Vasen HF, Blanco I, Aktan-Collan K, Gopie JP, Alonso A, et al. (2013) Revised guidelines for the clinical management of Lynch syndrome (HNPCC): recommendations by a group of European experts. Gut 62: 812-823.
3. Järvinen HJ, Aarnio M, Mustonen H, Aktan-Collan K, Aaltonen LA, et al. (2000) Controlled 15-year trial on screening for colorectal cancer in families with hereditary nonpolyposis colorectal cancer. Gastroenterology 118: 829-834.
4. Järvinen HJ, Renkonen-Sinisalo L, Aktán-Collán K, Peltomäki P, Aaltonen LA, et al. (2009) Ten years after mutation testing for Lynch syndrome: cancer incidence and outcome in mutation-positive and mutation-negative family members. J Clin Oncol 27: 4793-4797.
5. Schmeler KM, Lynch HT, Chen LM, Munsell MF, Soliman PT, et al. (2006) Prophylactic surgery to reduce the risk of gynecologic cancers in the Lynch syndrome. N Engl J Med 354: 261-269.
6. Lu KH, Loose DS, Yates MS, Nogueras-Gonzalez GM, Munsell MF, et al. (2013) Prospective, multi-center randomized intermediate biomarker study of oral contraceptive vs. depo-provera for prevention of endometrial cancer in women with Lynch Syndrome. Cancer Prev Res 0020.
7. U.S. Preventive Services Task Force (2006) Genetic risk assessment and BRCA mutation testing for breast and ovarian cancer susceptibility: recommendation statement. Ann Intern Med 73: 869-874.
8. Singh H, Schiesser R, Anand G, Richardson PA, El-Serag HB (2010) Underdiagnosis of Lynch syndrome involves more than family history criteria. Clin Gastroenterol Hepatol 8: 523-529.
9. White DB, Bonham VL, Jenkins J, Stevens N, McBride CM (2008) Too many referrals of low-risk women for BRCA1/2 genetic services by family physicians. Cancer Epidemiol Biomarkers Prev 17: 2980-2986.
10. Sweet KM, Bradley TL, Westman JA (2002) Identification and referral of families at high risk for cancer susceptibility. J Clin Oncol 20: 528-537.
11. Wong C, Gibbs P, Johns J, Jones I, Faragher I, et al. (2008) Value of database linkage: are patients at risk of familial colorectal cancer being referred for genetic counselling and testing? Intern Med J 38: 328-333.
12. Schofield L, Grieu F, Goldblatt J, Amanuel B, Iacopetta B (2012) A state-wide population-based program for detection of lynch syndrome based upon immunohistochemical and molecular testing of colorectal tumours. Fam Cancer 11: 1-6.
13. Tan YY, McGaughran J, Ferguson K, Walsh MD, Buchanan DD, et al. (2013) Improving identification of lynch syndrome patients: a comparison of research data with clinical records. Int J Cancer 132: 2876-2883.
14. Scheuner MT, Sieverding P, Shekelle PG (2008) Delivery of genomic medicine for common chronic adult diseases: a systematic review. JAMA 299: 1320-1334.
15. Suther S, Goodson P (2003) Barriers to the provision of genetic services by primary care physicians: a systematic review of the literature. Genet Med 5: 70-76.
16. Qureshi N, Wilson B, Santaguida P, Carroll J, Allanson J, et al. (2007) Collection and use of cancer family history in primary care. Evid Rep Technol Assess (Full Rep) : 1-84.
17. Vig HS, Armstrong J, Egleston BL, Mazar C, Toscano M, et al. (2009) Cancer genetic risk assessment and referral patterns in primary care. Genet Test Mol Biomarkers 13: 735-741.
18. Brandt R, Ali Z, Sabel A, McHugh T, Gilman P (2008) Cancer genetics evaluation: barriers to and improvements for referral. Genet Test 12: 9-12.
19. Sifri R, Myers R, Hyslop T, Turner B, Cocroft J, et al. (2003) Use of cancer susceptibility testing among primary care physicians. Clin Genet 64: 355-360.
20. Wideroff L, Freedman AN, Olson L, Klabunde CN, Davis W, et al. (2003) Physician use of genetic testing for cancer susceptibility: results of a national survey. Cancer Epidemiol Biomarkers Prev 12: 295-303.
21. Batra S, Valdimarsdottir H, McGovern M, Itzkowitz S, Brown K (2002) Awareness of genetic testing for colorectal cancer predisposition among specialists in gastroenterology. Am J Gastroenterol 97: 729-733.
22. Wilkins-Haug L, Erickson K, Hill L, Power M, Holzman GB, et al. (2000) Obstetrician-gynecologists' opinions and attitudes on the role of genetics in women's health. J Womens Health Gend Based Med 9: 873-879.
23. Acton RT, Burst NM, Casebeer L, Ferguson SM, Greene P, et al. (2000) Knowledge, attitudes, and behaviors of Alabama's primary care physicians regarding cancer genetics. Acad Med 75: 850-852.
24. Hayflick SJ, Eiff MP, Carpenter L, Steinberger J (1998) Primary care physicians' utilization and perceptions of genetics services. Genet Med 1: 13-21.
25. Murff HJ, Byrne D, Syngal S (2004) Cancer risk assessment: quality and impact of the family history interview. Am J Prev Med 27: 239-245.
26. Grover S, Stoffel EM, Bussone L, Tschoegl E, Syngal S (2004) Physician assessment of family cancer history and referral for genetic evaluation in colorectal cancer patients. Clin Gastroenterol Hepatol 2: 813-819.
27. Al-Habsi H, Lim JN, Chu CE, Hewison J (2008) Factors influencing the referrals in primary care of asymptomatic patients with a family history of cancer. Genet Med 10: 751-757.
28. Burke W, Culver J, Pinsky L, Hall S, Reynolds SE, et al. (2009) Genetic assessment of breast cancer risk in primary care practice. Am J Med Genet A 149A: 349-356.
29. Koil CE, Everett JN, Hoechstetter L, Ricer RE, Huelsman KM (2003) Differences in physician referral practices and attitudes regarding hereditary breast cancer by clinical practice location. Genet Med 5: 364-369.
30. Claybrook J, Hunter C, Wetherill LF, Vance GH (2010) Referral patterns of Indiana oncologists for colorectal cancer genetic services. J Cancer Educ 25: 92-95.
31. Fry A, Campbell H, Gudmunsdottir H, Rush R, Porteous M, et al. (1999) GPs' views on their role in cancer genetics services and current practice. Fam Pract 16: 468-474.
32. Tomatir AG, Sorkun HC, Demirhan H, AkdaÄŸ B (2007) Genetics and genetic counseling: practices and opinions of primary care physicians in Turkey. Genet Med 9: 130-135.
33. Mehnert A, Bergelt C, Koch U (2003) Knowledge and attitudes of gynecologists regarding genetic counseling for hereditary breast and ovarian cancer. Patient Educ Couns 49: 183-188.
34. Kelly KM, Love MM, Pearce KA, Porter K, Barron MA, et al. (2009) Cancer risk assessment by rural and Appalachian family medicine physicians. J Rural Health 25: 372-377.
35. Taylor MR, Edwards JG, Ku L (2006) Lost in transition: challenges in the expanding field of adult genetics. Am J Med Genet C Semin Med Genet 142C: 294-303.
36. Acheson LS, Stange KC, Zyzanski S (2005) Clinical genetics issues encountered by family physicians. Genet Med 7: 501-508.
37. Cox SL, Zlot AI, Silvey K, Elliott D, Horn T, et al. (2012) Patterns of cancer genetic testing: a randomized survey of Oregon clinicians. J Cancer Epidemiol 2012: 294730.
38. Prochniak CF, Martin LJ, Miller EM, Knapke SC (2012) Barriers to and motivations for physician referral of patients to cancer genetics clinics. J Genet Couns 21: 305-325.
39. Bellcross CA, Kolor K, Goddard KA, Coates RJ, Reyes M, et al. (2011) Awareness and utilization of BRCA1/2 testing among U.S. primary care physicians. Am J Prev Med 40: 61-66.
40. Domanska K, Carlsson C, Bendahl PO, Nilbert M (2009) Knowledge about hereditary nonpolyposis colorectal cancer; mutation carriers and physicians at equal levels. BMC Med Genet 10: 30.
41. Carroll JC, Cappelli M, Miller F, Wilson BJ, Grunfeld E, et al. (2008) Genetic services for hereditary breast/ovarian and colorectal cancers - physicians' awareness, use and satisfaction. Community Genet 11: 43-51.
42. Wideroff L, Vadaparampil ST, Greene MH, Taplin S, Olson L, et al. (2005) Hereditary breast/ovarian and colorectal cancer genetics knowledge in a national sample of US physicians. J Med Genet 42: 749-755.
43. McCann S, MacAuley D, Barnett Y (2005) Genetic consultations in primary care: GPs' responses to three scenarios. Scand J Prim Health Care 23: 109-114.
44. Morgan S, McLeod D, Kidd A, Langford B (2004) Genetic testing in New Zealand: the role of the general practitioner. N Z Med J 117: U1178.
45. Welkenhuysen M, Evers-Kiebooms G. (2003) The reactions of general practitioners, nurses and midwives in Flanders concerning breast cancer risks in a high-risk situation. Community Genet. 6: 206-213.
46. Pichert G, Dietrich D, Moosmann P, Zwahlen M, Stahel RA, et al. (2003) Swiss primary care physicians' knowledge, attitudes and perception towards genetic testing for hereditary breast cancer. Fam Cancer 2: 153-158.
47. Doksum T, Bernhardt BA, Holtzman NA (2003) Does knowledge about the genetics of breast cancer differ between nongeneticist physicians who do or do not discuss or order BRCA testing? Genet Med 5: 99-105.
48. McCann S, Macauley D, Barnett Y. (2002) General Practitioners and Genes Perceived Roles, Confidence and Satisfaction with Knowledge. The European Journal of General Practice. 8: 140-145.
49. Menasha JD, Schechter C, Willner J (2000) Genetic testing: a physician's perspective. Mt Sinai J Med 67: 144-151.
50. Escher M, Sappino AP (2000) Primary care physicians' knowledge and attitudes towards genetic testing for breast-ovarian cancer predisposition. Ann Oncol 11: 1131-1135.
51. Rowley PT, Loader S (1996) Attitudes of obstetrician-gynecologists toward DNA testing for a genetic susceptibility to breast cancer. Obstet Gynecol 88: 611-615.
52. Carroll JC, Brown JB, Blaine S, Glendon G, Pugh P, et al. (2003) Genetic susceptibility to cancer. Family physicians' experience. Can Fam Physician 49: 45-52.
53. Friedman L, Cooper HP, Webb JA, Weinberg AD, Plon SE (2003) Primary care physicians' attitudes and practices regarding cancer genetics: a comparison of 2001 with 1996 survey results. J Cancer Educ 18: 91-94.
54. Freedman AN, Wideroff L, Olson L, Davis W, Klabunde C, et al. (2003) US physicians' attitudes toward genetic testing for cancer susceptibility. Am J Med Genet A 120A: 63-71.
55. Friedman LC, Plon SE, Cooper HP, Weinberg AD (1997) Cancer genetics--survey of primary care physicians' attitudes and practices. J Cancer Educ 12: 199-203.
56. Mountcastle-Shah E, Holtzman NA (2000) Primary care physicians' perceptions of barriers to genetic testing and their willingness to participate in research. Am J Med Genet 94: 409-416.
57. Bathurst L, Huang QR (2006) A qualitative study of GPs' views on modern genetics. Aust Fam Physician 35: 462-464.
58. Win AK, Lindor NM, Winship I, Tucker KM, Buchanan DD, et al. (2013) Risks of colorectal and other cancers after endometrial cancer for women with Lynch syndrome. J Natl Cancer Inst 105: 274-279.
59. Win AK, Young JP, Lindor NM, Tucker KM, Ahnen DJ, et al. (2012) Colorectal and other cancer risks for carriers and noncarriers from families with a DNA mismatch repair gene mutation: a prospective cohort study. J Clin Oncol 30: 958-964.
60. Pande M, Wei C, Chen J, Amos CI, Lynch PM, et al. (2012) Cancer spectrum in DNA mismatch repair gene mutation carriers: results from a hospital based Lynch syndrome registry. Fam Cancer 11: 441-447.
61. Qureshi N, Wilson B, Santaguida P, Little J, Carroll J, et al. (2009) Family history and improving health. Evid Rep Technol Assess 186: 1-135.
62. Wilson BJ, Qureshi N, Santaguida P, Little J, Carroll JC, et al. (2009) Systematic review: family history in risk assessment for common diseases. Ann Intern Med 151: 878-885.
63. Orlando LA, Hauser ER, Christianson C, Powell KP, Buchanan AH, et al. (2011) Protocol for implementation of family health history collection and decision support into primary care using a computerized family health history system. BMC Health Serv Res 11: 264.
64. Moreira L, Balaguer F, Lindor N, de la Chapelle A, Hampel H, et al. (2012) Identification of Lynch syndrome among patients with colorectal cancer. JAMA 308: 1555-1565.
65. Perez-C L, Ruiz PC, Guarinos C, Alenda C, Paya A, et al. (2011) Comparison between universal molecular screening for Lynch syndrome and revised Bethesda guidelines in a large population-based cohort of patients with colorectal cancer. Gut. 61: 865-872.
66. Kwon JS, Scott JL, Gilks CB, Daniels MS, Sun CC, et al. (2011) Testing women with endometrial cancer to detect Lynch syndrome. J Clin Oncol 29: 2247-2252.
67. Emery J (2005) The GRAIDS Trial: the development and evaluation of computer decision support for cancer genetic risk assessment in primary care. Ann Hum Biol 32: 218-227.
68. Battista RN, Blancquaert I, Laberge AM, van Schendel N, Leduc N (2012) Genetics in health care: an overview of current and emerging models. Public Health Genomics 15: 34-45.
69. Emery J, Watson E, Rose P, Andermann A (1999) A systematic review of the literature exploring the role of primary care in genetic services. Fam Pract 16: 426-445.
70. Lucassen A, Watson E, Harcourt J, Rose P, O'Grady J (2001) Guidelines for referral to a regional genetics service: GPs respond by referring more appropriate cases. Fam Pract 18: 135-140.