Expert consensus on genetic counseling in gynecological oncology (2023 edition)

doi:10.19401/j.cnki.1007-3639.2023.11.010

Abstract

Abstract:

With the increasing applications of high-throughput genome sequencing technology, there is a growing recognition of the important roles of genetic factors in the occurrence and development of gynecological tumors. Genetic counseling is widely adopted in various aspects of precision medicine in tumor screening, diagnosis, treatment and prevention. From March to September 2023, more than 20 clinical experts in gynecological oncology from Gynecologic Oncology Genetic Counseling Collaboration Group, Chinese Tertiary Obstetrics and Gynecology Hospital/Materning and Child Healthcare Hospital Alliance and Integrated Chinese and Western Endometrial Cancer Professional Committee, Chinese Anti-Cancer Association, collaborated with multidisciplinary experts in epidemiology and evidence-based medicine research. Together, We conducted preliminary research on clinical issues, held special meetings with methodology experts, and convened extensive discussions with the clinical experts in gynecological oncology to draft the “expert consensus on genetic counseling in gynecological oncology (2023 edition)”. This consensus covers various aspects, including the background, characteristics and common types of hereditary tumors, genetic tumor testing, eligible populations for genetic counseling, the process and content of genetic counseling, as well as recommended resources. It follows the evidence grading system of the Oxford Centre for Evidence-Based Medicine and ultimately presents 16 expert consensus statements and recommendations. We hope that this consensus will empower clinical practitioner in gynecological oncology to better identify hereditary tumors, enabling them to provide more accurate diagnosis and treatment for patients, as well as effective preventative measures and reproductive management for their family members. This consensus will be periodically updated to align with the advancements in diagnosis and treatment of gynecological tumors and genetic counseling related fields.

Key words: Gynecological oncology, Genetic factors, Genetic counseling, Expert consensus

CLC Number:

R737.3

Figures/Tables 1

References 124

[1]	SUNG H, FERLAY J, SIEGEL R L, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71(3): 209-249. doi: 10.3322/caac.v71.3
[2]	World Health Organization. Cancer topics[EB/OL].[2023-08-11]. https://www.iarc.who.int/cancer-topics/.
[3]	CHEN M, ZHAO H Y. Next-generation sequencing in liquid biopsy: cancer screening and early detection[J]. Hum Genomics, 2019, 13(1): 34. doi: 10.1186/s40246-019-0220-8 pmid: 31370908
[4]	GUZAUSKAS G F, GARBETT S, ZHOU Z L, et al. Population genomic screening for three common hereditary conditions: a cost-effectiveness analysis[J]. Ann Intern Med, 2023, 176(5): 585-595. doi: 10.7326/M22-0846
[5]	DEVLIN L A, MORRISON P J. Inherited gynaecological cancer syndromes[J]. Obstet Gynaecol, 2008, 10(1): 9-15. doi: 10.1576/toag.10.1.009.27371
[6]	Hereditary cancer syndromes and risk assessment: ACOG COMMITTEE OPINION, number 793[J]. Obstet Gynecol, 2019, 134(6): e143-e149. doi: 10.1097/AOG.0000000000003563
[7]	KOSTOV S, WATROWSKI R, KORNOVSKI Y, et al. Hereditary gynecologic cancer syndromes-a narrative review[J]. Onco Targets Ther, 2022, 15: 381-405. doi: 10.2147/OTT.S353054
[8]	MURRAY M F, KHOURY M J, ABUL-HUSN N S. Addressing the routine failure to clinically identify monogenic cases of common disease[J]. Genome Med, 2022, 14(1): 60. doi: 10.1186/s13073-022-01062-6 pmid: 35672798
[9]	RANDALL L M, POTHURI B. The genetic prediction of risk for gynecologic cancers[J]. Gynecol Oncol, 2016, 141(1): 10-16. doi: 10.1016/j.ygyno.2016.03.007 pmid: 27016223
[10]	FANALE D, PIVETTI A, CANCELLIERE D, et al. BRCA1/2 variants of unknown significance in hereditary breast and ovarian cancer (HBOC) syndrome: looking for the hidden meaning[J]. Crit Rev Oncol Hematol, 2022, 172: 103626. doi: 10.1016/j.critrevonc.2022.103626
[11]	LU K H. Hereditary gynecologic cancers: differential diagnosis, surveillance, management and surgical prophylaxis[J]. Fam Cancer, 2008, 7(1): 53-58. doi: 10.1007/s10689-007-9144-x pmid: 17636427
[12]	SHANBHOGUE K P, PRASAD A S, UCISIK-KESER F E, et al. Hereditary ovarian tumour syndromes: current update on genetics and imaging[J]. Clin Radiol, 2021, 76(4): 313. e15-313.313.e26.
[13]	UEKI A, HIRASAWA A. Molecular features and clinical management of hereditary gynecological cancers[J]. Int J Mol Sci, 2020, 21(24): 9504. doi: 10.3390/ijms21249504
[14]	KATABATHINA V S, MENIAS C O, KHANNA L, et al. Hereditary gastrointestinal cancer syndromes: role of imaging in screening, diagnosis, and management[J]. Radiographics, 2019, 39(5): 1280-1301. doi: 10.1148/rg.2019180185 pmid: 31373866
[15]	MANNING-GEIST B L, GATIUS S, LIU Y, et al. Diagnosis and management of an endometrial cancer patient with Cowden syndrome[J]. Gynecol Oncol, 2021, 163(1): 14-21. doi: 10.1016/j.ygyno.2021.08.008
[16]	LU G H. Hereditary cancer genetic counseling[M]. Beijing: Peking University Medical Press, 2021: 261-292.
[17]	NEMES K, FRÜHWALD M C. Emerging therapeutic targets for the treatment of malignant rhabdoid tumors[J]. Expert Opin Ther Targets, 2018, 22(4): 365-379. doi: 10.1080/14728222.2018.1451839
[18]	SCHULTZ K A P, STEWART D R, KAMIHARA J, et al. DICER1 Tumor Predisposition[DB/OL]. (2020-04-30)[2023-08-11]. https://www.ncbi.nlm.nih.gov/books/NBK196157/.
[19]	DHO Y S, KIM S K, CHEON J E, et al. Investigation of the location of atypical teratoid/rhabdoid tumor[J]. Childs Nerv Syst, 2015, 31(8): 1305-1311. doi: 10.1007/s00381-015-2739-x
[20]	LINDOR N M, MCMASTER M L, LINDOR C J, et al. Concise handbook of familial cancer susceptibility syndromes-second edition[J]. J Natl Cancer Inst Monogr, 2008(38): 1-93.
[21]	HILGART J S, HAYWARD J A, COLES B, et al. Telegenetics: a systematic review of telemedicine in genetics services[J]. Genet Med, 2012, 14(9): 765-776. doi: 10.1038/gim.2012.40 pmid: 22498847
[22]	BAUMANIS L, EVANS J P, CALLANAN N, et al. Telephoned BRCA1/2 genetic test results: prevalence, practice, and patient satisfaction[J]. J Genet Couns, 2009, 18(5): 447-463. doi: 10.1007/s10897-009-9238-8
[23]	GRAY J, BRAIN K, IREDALE R, et al. A pilot study of telegenetics[J]. J Telemed Telecare, 2000, 6(4): 245-247. pmid: 11027129
[24]	KINNEY A Y, BUTLER K M, SCHWARTZ M D, et al. Expanding access to BRCA1/2 genetic counseling with telephone delivery: a cluster randomized trial[J]. J Natl Cancer Inst, 2014, 106(12): dju328. doi: 10.1093/jnci/dju328
[25]	BRACKE X, ROBERTS J, MCVEIGH T P. A systematic review and meta-analysis of telephone vs in-person genetic counseling in BRCA1/BRCA2 genetic testing[J]. J Genet Couns, 2021, 30(2): 563-573. doi: 10.1002/jgc4.v30.2
[26]	GATTAS M R, MACMILLAN J C, MEINECKE I, et al. Telemedicine and clinical genetics: establishing a successful service[J]. J Telemed Telecare, 2001, 7(Suppl 2): 68-70.
[27]	COELHO J J, ARNOLD A, NAYLER J, et al. An assessment of the efficacy of cancer genetic counselling using real-time videoconferencing technology (telemedicine) compared to face-to-face consultations[J]. Eur J Cancer, 2005, 41(15): 2257-2261. pmid: 16176873
[28]	ZILLIACUS E M, MEISER B, LOBB E A, et al. Are videoconferenced consultations as effective as face-to-face consultations for hereditary breast and ovarian cancer genetic counseling?[J]. Genet Med, 2011, 13(11): 933-941. doi: 10.1097/GIM.0b013e3182217a19 pmid: 21799430
[29]	SENTER L, O’MALLEY D M, BACKES F J, et al. Genetic consultation embedded in a gynecologic oncology clinic improves compliance with guideline-based care[J]. Gynecol Oncol, 2017, 147(1): 110-114. doi: S0090-8258(17)31182-4 pmid: 28800943
[30]	RANA H Q, KIPNIS L, HEHIR K, et al. Embedding a genetic counselor into oncology clinics improves testing rates and timeliness for women with ovarian cancer[J]. Gynecol Oncol, 2021, 160(2): 457-463. doi: 10.1016/j.ygyno.2020.11.003 pmid: 33229043
[31]	KENTWELL M, DOW E, ANTILL Y, et al. Mainstreaming cancer genetics: a model integrating germline BRCA testing into routine ovarian cancer clinics[J]. Gynecol Oncol, 2017, 145(1): 130-136.
[32]	MÁRQUEZ-RODAS I, LÓPEZ-TRABADA D, RUPÉREZ BLANCO A B, et al. Family history record and hereditary cancer risk perception according to National Cancer Institute criteria in a Spanish medical oncology service: a retrospective study[J]. Oncology, 2012, 82(1): 30-34. doi: 10.1159/000335960
[33]	OW S G, YONG Y F, CHIENG W S, et al. Inadequate family history assessment by oncologists is an important physician barrier to referral for hereditary breast cancer evaluation[J]. Clin Oncol (R Coll Radiol), 2014, 26(3): 174-175. doi: 10.1016/j.clon.2013.11.029 pmid: 24393786
[34]	BORRY P, STULTIENS L, NYS H, et al. Presymptomatic and predictive genetic testing in minors: a systematic review of guidelines and position papers[J]. Clin Genet, 2006, 70(5): 374-381. pmid: 17026616
[35]	EIJZENGA W, DE GEUS E, AALFS C M, et al. How to support cancer genetics counselees in informing at-risk relatives? Lessons from a randomized controlled trial[J]. Patient Educ Couns, 2018, 101(9): 1611-1619. doi: S0738-3991(18)30206-4 pmid: 29789176
[36]	OFFIT K, LEVRAN O, MULLANEY B, et al. Shared genetic susceptibility to breast cancer, brain tumors, and Fanconi anemia[J]. J Natl Cancer Inst, 2003, 95(20): 1548-1551. pmid: 14559878
[37]	FANALE D, FIORINO A, INCORVAIA L, et al. Prevalence and spectrum of germline BRCA1 and BRCA2 variants of uncertain significance in breast/ovarian cancer: mysterious signals from the genome[J]. Front Oncol, 2021, 11: 682445. doi: 10.3389/fonc.2021.682445
[38]	HEGDE M, FERBER M, MAO R, et al. ACMG technical standards and guidelines for genetic testing for inherited colorectal cancer (Lynch syndrome, familial adenomatous polyposis, and MYH-associated polyposis)[J]. Genet Med, 2014, 16(1): 101-116. doi: 10.1038/gim.2013.166 pmid: 24310308
[39]	《基于下一代测序技术的BRCA1/2基因检测指南(2019版)》编写组. 基于下一代测序技术的BRCA1/2基因检测指南(2019版)[J]. 中华病理学杂志, 2019, 48(9): 670-677.
	“Guidelines for genetic testing of BRCA1/2 genes based on next-generation sequencing technology (2019 edition)” Working Group. Guidelines for genetic testing of BRCA1/2 genes based on next-generation sequencing technology (2019 edition)[J]. Chin J Pathol, 2019, 48(9): 670-677.
[40]	MILLER D T, LEE K, ABUL-HUSN N S, et al. ACMG SF v3.1 list for reporting of secondary findings in clinical exome and genome sequencing: a policy statement of the American College of Medical Genetics and Genomics (ACMG)[J]. Genet Med, 2022, 24(7): 1407-1414. doi: 10.1016/j.gim.2022.04.006 pmid: 35802134
[41]	REHDER C, BEAN L J H, BICK D, et al. Next-generation sequencing for constitutional variants in the clinical laboratory, 2021 revision: a technical standard of the American College of Medical Genetics and Genomics (ACMG)[J]. Genet Med, 2021, 23(8): 1399-1415. doi: 10.1038/s41436-021-01139-4 pmid: 33927380
[42]	SONG C, DUZKALE H, SHEN J. Reporting of clinical genome sequencing results[J]. Curr Protoc Hum Genet, 2018, 98(1): e61.
[43]	张军玉, 沈亦平. 全面认识遗传检测[J]. 中国实用儿科杂志, 2022, 37(4): 272-276.
	ZHANG J Y, SHEN Y P. A comprehensive understanding of genetic testing[J]. Chin J Pract Pediatr, 2022, 37(4): 272-276.
[44]	GAYTHER S A, PHAROAH P D P. The inherited genetics of ovarian and endometrial cancer[J]. Curr Opin Genet Dev, 2010, 20(3): 231-238. doi: 10.1016/j.gde.2010.03.001 pmid: 20456938
[45]	JONES M A, TIMMS K M, HATCHER S, et al. The landscape of BRCA1 and BRCA2 large rearrangements in an international cohort of over 20 000 ovarian tumors identified using next-generation sequencing[J]. Genes Chromosomes Cancer, 2023, 62(10): 589-596. doi: 10.1002/gcc.v62.10
[46]	FAYER S, HORTON C, DINES J N, et al. Closing the gap: systematic integration of multiplexed functional data resolves variants of uncertain significance in BRCA1, TP53, and PTEN[J]. Am J Hum Genet, 2021, 108(12): 2248-2258. doi: 10.1016/j.ajhg.2021.11.001
[47]	RICHARDS S, AZIZ N, BALE S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology[J]. Genet Med, 2015, 17(5): 405-424. doi: 10.1038/gim.2015.30 pmid: 25741868
[48]	TAVTIGIAN S V, HARRISON S M, BOUCHER K M, et al. Fitting a naturally scaled point system to the ACMG/AMP variant classification guidelines[J]. Hum Mutat, 2020, 41(10): 1734-1737. doi: 10.1002/humu.v41.10
[49]	MERSCH J, BROWN N, PIRZADEH-MILLER S, et al. Prevalence of variant reclassification following hereditary cancer genetic testing[J]. JAMA, 2018, 320(12): 1266-1274. doi: 10.1001/jama.2018.13152 pmid: 30264118
[50]	ESTERLING L, WIJAYATUNGE R, BROWN K, et al. Impact of a cancer gene variant reclassification program over a 20-year period[J]. JCO Precis Oncol, 2020, 4: PO.20.00020.
[51]	ZHANG J, YAO Y, HE H, et al. Clinical interpretation of sequence variants[J]. Curr Protoc Hum Genet, 2020, 106(1): e98.
[52]	KATZ A E, NUSSBAUM R L, SOLOMON B D, et al. Management of secondary genomic findings[J]. Am J Hum Genet, 2020, 107(1): 3-14. doi: S0002-9297(20)30149-X pmid: 32619490
[53]	MURRAY M F, GIOVANNI M A, DOYLE D L, et al. DNA-based screening and population health: a points to consider statement for programs and sponsoring organizations from the American College of Medical Genetics and Genomics (ACMG)[J]. Genet Med, 2021, 23(6): 989-995. doi: 10.1038/s41436-020-01082-w pmid: 33727704
[54]	KOTSOPOULOS J, GRONWALD J, KARLAN B, et al. Age-specific ovarian cancer risks among women with a BRCA1 or BRCA2 mutation[J]. Gynecol Oncol, 2018, 150(1): 85-91. doi: 10.1016/j.ygyno.2018.05.011
[55]	ANTONIOU A, PHAROAH P D, NAROD S, et al. Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case Series unselected for family history: a combined analysis of 22 studies[J]. Am J Hum Genet, 2003, 72(5): 1117-1130. doi: 10.1086/375033
[56]	CHEN S N, IVERSEN E S, FRIEBEL T, et al. Characterization of BRCA1 and BRCA2 mutations in a large United States sample[J]. J Clin Oncol, 2006, 24(6): 863-871. doi: 10.1200/JCO.2005.03.6772
[57]	BROSE M S, REBBECK T R, CALZONE K A, et al. Cancer risk estimates for BRCA1 mutation carriers identified in a risk evaluation program[J]. J Natl Cancer Inst, 2002, 94(18): 1365-1372. doi: 10.1093/jnci/94.18.1365
[58]	VAN ASPEREN C J, BROHET R M, MEIJERS-HEIJBOER E J, et al. Cancer risks in BRCA2 families: estimates for sites other than breast and ovary[J]. J Med Genet, 2005, 42(9): 711-719. doi: 10.1136/jmg.2004.028829
[59]	CHEN S N, PARMIGIANI G. Meta-analysis of BRCA1 and BRCA2 penetrance[J]. J Clin Oncol, 2007, 25(11): 1329-1333. doi: 10.1200/JCO.2006.09.1066
[60]	MAVADDAT N, PEOCK S, FROST D, et al. Cancer risks for BRCA1 and BRCA2 mutation carriers: results from prospective analysis of EMBRACE[J]. J Natl Cancer Inst, 2013, 105(11): 812-822. doi: 10.1093/jnci/djt095
[61]	KUCHENBAECKER K B, HOPPER J L, BARNES D R, et al. Risks of breast, ovarian, and contralateral breast cancer for BRCA1 and BRCA2 mutation carriers[J]. JAMA, 2017, 317(23): 2402-2416. doi: 10.1001/jama.2017.7112
[62]	SEPPÄLÄ T T, DOMINGUEZ-VALENTIN M, SAMPSON J R, et al. Prospective observational data informs understanding and future management of Lynch syndrome: insights from the Prospective Lynch Syndrome Database (PLSD)[J]. Fam Cancer, 2021, 20(1): 35-39. doi: 10.1007/s10689-020-00193-2
[63]	HELDER-WOOLDERINK J M, BLOK E A, VASEN H F, et al. Ovarian cancer in Lynch syndrome; a systematic review[J]. Eur J Cancer, 2016, 55: 65-73. doi: 10.1016/j.ejca.2015.12.005
[64]	DOWTY J G, WIN A K, BUCHANAN D D, et al. Cancer risks for MLH1 and MSH2 mutation carriers[J]. Hum Mutat, 2013, 34(3): 490-497. doi: 10.1002/humu.22262
[65]	BONADONA V, BONAÏTI B, OLSCHWANG S, et al. Cancer risks associated with germline mutations in MLH1, MSH2, and MSH6 genes in Lynch syndrome[J]. JAMA, 2011, 305(22): 2304-2310. doi: 10.1001/jama.2011.743
[66]	DOMINGUEZ-VALENTIN M, SAMPSON J R, SEPPÄLÄ T T, et al. Cancer risks by gene, age, and gender in 6 350 carriers of pathogenic mismatch repair variants: findings from the Prospective Lynch Syndrome Database[J]. Genet Med, 2020, 22(1): 15-25.
[67]	MESERVE E E K, NUCCI M R. Peutz-Jeghers syndrome: pathobiology, pathologic manifestations, and suggestions for recommending genetic testing in pathology reports[J]. Surg Pathol Clin, 2016, 9(2): 243-268. doi: 10.1016/j.path.2016.01.006 pmid: 27241107
[68]	ISHIDA H, TAJIMA Y, GONDA T, et al. Update on our investigation of malignant tumors associated with Peutz-Jeghers syndrome in Japan[J]. Surg Today, 2016, 46(11): 1231-1242. doi: 10.1007/s00595-015-1296-y pmid: 26746637
[69]	TAN M H, MESTER J L, NGEOW J, et al. Lifetime cancer risks in individuals with germline PTEN mutations[J]. Clin Cancer Res, 2012, 18(2): 400-407. doi: 10.1158/1078-0432.CCR-11-2283
[70]	RAMUS S J, SONG H L, DICKS E, et al. Germline mutations in the BRIP1, BARD1, PALB2, and NBN genes in women with ovarian cancer[J]. J Natl Cancer Inst, 2015, 107(11): djv214.
[71]	KEMPERS M J, KUIPER R P, OCKELOEN C W, et al. Risk of colorectal and endometrial cancers in EPCAM deletion-positive Lynch syndrome: a cohort study[J]. Lancet Oncol, 2011, 12(1): 49-55. doi: 10.1016/S1470-2045(10)70265-5
[72]	YANG X, SONG H L, LESLIE G, et al. Ovarian and breast cancer risks associated with pathogenic variants in RAD51C and RAD51D[J]. J Natl Cancer Inst, 2020, 112(12): 1242-1250. doi: 10.1093/jnci/djaa030
[73]	GOGGINS M, OVERBEEK K A, BRAND R, et al. Management of patients with increased risk for familial pancreatic cancer: updated recommendations from the International Cancer of the Pancreas Screening (CAPS) Consortium[J]. Gut, 2020, 69(1): 7-17. doi: 10.1136/gutjnl-2019-319352 pmid: 31672839
[74]	HAN F F, GUO C L, LIU L H. The effect of CHEK2 variant I157T on cancer susceptibility: evidence from a meta-analysis[J]. DNA Cell Biol, 2013, 32(6): 329-335. doi: 10.1089/dna.2013.1970
[75]	JACOBS I J, MENON U, RYAN A, et al. Ovarian cancer screening and mortality in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial[J]. Lancet, 2016, 387(10022): 945-956. doi: S0140-6736(15)01224-6 pmid: 26707054
[76]	MENON U, GENTRY-MAHARAJ A, HALLETT R, et al. Sensitivity and specificity of multimodal and ultrasound screening for ovarian cancer, and stage distribution of detected cancers: results of the prevalence screen of the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS)[J]. Lancet Oncol, 2009, 10(4): 327-340. doi: 10.1016/S1470-2045(09)70026-9 pmid: 19282241
[77]	ROSENTHAL A N, FRASER L S M, PHILPOTT S, et al. Evidence of stage shift in women diagnosed with ovarian cancer during phase Ⅱ of the United Kingdom familial ovarian cancer screening study[J]. J Clin Oncol, 2017, 35(13): 1411-1420. doi: 10.1200/JCO.2016.69.9330
[78]	SKATES S J, GREENE M H, BUYS S S, et al. Early detection of ovarian cancer using the risk of ovarian cancer algorithm with frequent CA12-5 testing in women at increased familial risk-combined results from two screening trials[J]. Clin Cancer Res, 2017, 23(14): 3628-3637. doi: 10.1158/1078-0432.CCR-15-2750
[79]	National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology (NCCN guidelines®) genetic/familial high-risk assessment: colorectal version 1.2022[EB/OL]. (2023-02-10)[2023-08-11]. https://www.nccn.org/professionals/physician_gls/pdf/genetics_colon.pdf.
[80]	JACOBS I, GENTRY-MAHARAJ A, BURNELL M, et al. Sensitivity of transvaginal ultrasound screening for endometrial cancer in postmenopausal women: a case-control study within the UKCTOCS cohort[J]. Lancet Oncol, 2011, 12(1): 38-48. doi: 10.1016/S1470-2045(10)70268-0 pmid: 21147030
[81]	DOVE-EDWIN I, BOKS D, GOFF S, et al. The outcome of endometrial carcinoma surveillance by ultrasound scan in women at risk of hereditary nonpolyposis colorectal carcinoma and familial colorectal carcinoma[J]. Cancer, 2002, 94(6): 1708-1712. doi: 10.1002/cncr.v94:6
[82]	RENKONEN-SINISALO L, BÜTZOW R, LEMINEN A, et al. Surveillance for endometrial cancer in hereditary nonpolyposis colorectal cancer syndrome[J]. Int J Cancer, 2007, 120(4): 821-824. doi: 10.1002/ijc.v120:4
[83]	SROCZYNSKI G, GOGOLLARI A, CONRADS-FRANK A, et al. Cost-effectiveness of early detection and prevention strategies for endometrial cancer-a systematic review[J]. Cancers (Basel), 2020, 12(7): 1874. doi: 10.3390/cancers12071874
[84]	LEE M H, KIM E S, CHOI M C, et al. Minimal deviation adenocarcinoma (adenoma malignum) of the uterine cervix: clinicopathological analysis of 17 cases[J]. Obstet Gynecol Sci, 2018, 61(5): 590-597. doi: 10.5468/ogs.2018.61.5.590 pmid: 30254995
[85]	王文莉, 叶红. Peutz-Jeghers综合征相关宫颈胃型腺癌的研究进展[J]. 中国微创外科杂志, 2022, 22(2): 167-169.
	WANG W L, YE H. Research progress of cervical gastric type adenocarcinoma associated with Peutz-Jeghers syndrome[J]. Chin J Min Inv Surg, 2022, 22(2): 167-169.
[86]	PATNICK J, LANCUCKI L. Cervical screening programme, England: 1997-1998[J]. J Med Screen, 1999, 6(2): 57. doi: 10.1136/jms.6.2.57
[87]	SENGUPTA S, BOSE S. Peutz-Jeghers syndrome[J]. N Engl J Med, 2019, 380(5): 472. doi: 10.1056/NEJMicm1806623
[88]	MONK B J, PARKINSON C, LIM M C, et al. A randomized, phase Ⅲ trial to evaluate rucaparib monotherapy as maintenance treatment in patients with newly diagnosed ovarian cancer (ATHENA-MONO/GOG-3020/ENGOT-ov45)[J]. J Clin Oncol, 2022, 40(34): 3952-3964. doi: 10.1200/JCO.22.01003
[89]	OAKNIN A, GILBERT L, TINKER A V, et al. Safety and antitumor activity of dostarlimab in patients with advanced or recurrent DNA mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) or proficient/stable (MMRp/MSS) endometrial cancer: interim results from GARNET-a phase Ⅰ, single-arm study[J]. J Immunother Cancer, 2022, 10(1): e003777. doi: 10.1136/jitc-2021-003777
[90]	PETERS S, CHO B C, LUFT A, et al. Association between KRAS/STK11/KEAP1 mutations and outcomes in POSEIDON: durvalumab±tremelimumab+chemotherapy in mNSCLC[C]. Vienna:2022 World Conference on Lung Cancer, 2022: abstract 1220.
[91]	ELEJE G U, EKE A C, EZEBIALU I U, et al. Risk-reducing bilateral salpingo-oophorectomy in women with BRCA1 or BRCA2 mutations[J]. Cochrane Database Syst Rev, 2018, 8(8): CD012464.
[92]	LIU Y L, BREEN K, CATCHINGS A, et al. Risk-reducing bilateral salpingo-oophorectomy for ovarian cancer: a review and clinical guide for hereditary predisposition genes[J]. JCO Oncol Pract, 2022, 18(3): 201-209.
[93]	CHEN L M, BLANK S V, BURTON E, et al. Reproductive and hormonal considerations in women at increased risk for hereditary gynecologic cancers: society of gynecologic oncology and American Society for Reproductive Medicine Evidence-based review[J]. Gynecol Oncol, 2019, 155(3): 508-514. doi: 10.1016/j.ygyno.2019.06.017
[94]	STANCIU P I, IND T E J, BARTON D P J, et al. Development of peritoneal carcinoma in women diagnosed with serous tubal intraepithelial carcinoma (STIC) following risk-reducing salpingo-oophorectomy (RRSO)[J]. J Ovarian Res, 2019, 12(1): 50. doi: 10.1186/s13048-019-0525-1 pmid: 31128592
[95]	PINSKY P F, YU K, KRAMER B S, et al. Extended mortality results for ovarian cancer screening in the PLCO trial with median 15 years follow-up[J]. Gynecol Oncol, 2016, 143(2): 270-275. doi: 10.1016/j.ygyno.2016.08.334
[96]	SCHMELER K M, LYNCH H T, CHEN L M, et al. Prophylactic surgery to reduce the risk of gynecologic cancers in the Lynch syndrome[J]. N Engl J Med, 2006, 354(3): 261-269. doi: 10.1056/NEJMoa052627
[97]	CAPASSO I, SANTORO A, LUCCI CORDISCO E, et al. Lynch syndrome and gynecologic tumors: incidence, prophylaxis, and management of patients with cancer[J]. Cancers (Basel), 2023, 15(5): 1400. doi: 10.3390/cancers15051400
[98]	SMERDEL M P, SKYTTE A B, JELSIG A M, et al. Revised Danish guidelines for the cancer surveillance of patients with Cowden Syndrome[J]. Eur J Med Genet, 2020, 63(5): 103873. doi: 10.1016/j.ejmg.2020.103873
[99]	SERACCHIOLI R, COLOMBO F M, BAGNOLI A, et al. Primary ovarian leiomyosarcoma as a new component in the nevoid basal cell carcinoma syndrome: a case report[J]. Am J Obstet Gynecol, 2003, 188(4): 1093-1095. pmid: 12712116
[100]	FOULKES W D, KAMIHARA J, EVANS D G R, et al. Cancer surveillance in gorlin syndrome and rhabdoid tumor predisposition syndrome[J]. Clin Cancer Res, 2017, 23(12): e62-e67. doi: 10.1158/1078-0432.CCR-17-0595
[101]	MULLER M, FERLICOT S, GUILLAUD-BATAILLE M, et al. Reassessing the clinical spectrum associated with hereditary leiomyomatosis and renal cell carcinoma syndrome in French FH mutation carriers[J]. Clin Genet, 2017, 92(6): 606-615. doi: 10.1111/cge.13014 pmid: 28300276
[102]	TONOREZOS E S, FRIEDMAN D N, BARNEA D, et al. Recommendations for long-term follow-up of adults with heritable retinoblastoma[J]. Ophthalmology, 2020, 127(11): 1549-1557. doi: 10.1016/j.ophtha.2020.05.024 pmid: 32422154
[103]	SCHRIJVER L H, OLSSON H, PHILLIPS K A, et al. Oral contraceptive use and breast cancer risk: retrospective and prospective analyses from a BRCA1 and BRCA2 mutation carrier cohort study[J]. JNCI Cancer Spectr, 2018, 2(2): pky023.
[104]	SCHRIJVER L H, ANTONIOU A C, OLSSON H, et al. Oral contraceptive use and ovarian cancer risk for BRCA1/2 mutation carriers: an international cohort study[J]. Am J Obstet Gynecol, 2021, 225(1): 51. e1-51.51.e17.
[105]	李艳红, 姚元庆. 遗传性乳腺癌-卵巢癌综合征[J]. 中国实用妇科与产科杂志, 2006, 22(9): 709-710.
	LI Y H, YAO Y Q. Hereditary breast-ovarian cancer syndrome[J]. Chin J Pract Gynecol Obstet, 2006, 22(9): 709-710.
[106]	LU K H, LOOSE D S, YATES M S, et al. Prospective multicenter randomized intermediate biomarker study of oral contraceptive versus depo-provera for prevention of endometrial cancer in women with Lynch syndrome[J]. Cancer Prev Res (Phila), 2013, 6(8): 774-781. doi: 10.1158/1940-6207.CAPR-13-0020
[107]	ANDERSON K, JACOBSON J S, HEITJAN D F, et al. Cost-effectiveness of preventive strategies for women with a BRCA1 or a BRCA2 mutation[J]. Ann Intern Med, 2006, 144(6): 397-406.
[108]	GRANN V R, PATEL P R, JACOBSON J S, et al. Comparative effectiveness of screening and prevention strategies among BRCA1/2-affected mutation carriers[J]. Breast Cancer Res Treat, 2011, 125(3): 837-847. doi: 10.1007/s10549-010-1043-4
[109]	BOMMER C, LUPATSCH J, BÜRKI N, et al. Cost-utility analysis of risk-reducing strategies to prevent breast and ovarian cancer in BRCA-mutation carriers in Switzerland[J]. Eur J Health Econ, 2022, 23(5): 807-821. doi: 10.1007/s10198-021-01396-9
[110]	MANCHANDA R, LEGOOD R, ANTONIOU A C, et al. Specifying the ovarian cancer risk threshold of ‘premenopausal risk-reducing salpingo-oophorectomy’ for ovarian cancer prevention: a cost-effectiveness analysis[J]. J Med Genet, 2016, 53(9): 591-599. doi: 10.1136/jmedgenet-2016-103800
[111]	MANCHANDA R, LEGOOD R, PEARCE L, et al. Defining the risk threshold for risk reducing salpingo-oophorectomy for ovarian cancer prevention in low risk postmenopausal women[J]. Gynecol Oncol, 2015, 139(3): 487-494. doi: 10.1016/j.ygyno.2015.10.001 pmid: 26436478
[112]	SROCZYNSKI G, GOGOLLARI A, KUEHNE F, et al. A systematic review on cost-effectiveness studies evaluating ovarian cancer early detection and prevention strategies[J]. Cancer Prev Res (Phila), 2020, 13(5): 429-442. doi: 10.1158/1940-6207.CAPR-19-0506
[113]	ZEGERS-HOCHSCHILD F, ADAMSON G D, DYER S, et al. The international glossary on infertility and fertility care, 2017[J]. Hum Reprod, 2017, 32(9): 1786-1801. doi: 10.1093/humrep/dex234
[114]	GIETEL-HABETS J J, DE DIE-SMULDERS C E, DERKS-SMEETS I A, et al. Awareness and attitude regarding reproductive options of persons carrying a BRCA mutation and their partners[J]. Hum Reprod, 2017, 32(3): 588-597.
[115]	DERKS-SMEETS I A, GIETEL-HABETS J J, TIBBEN A, et al. Decision-making on preimplantation genetic diagnosis and prenatal diagnosis: a challenge for couples with hereditary breast and ovarian cancer[J]. Hum Reprod, 2014, 29(5): 1103-1112. doi: 10.1093/humrep/deu034
[116]	HODGE J G. Ethical issues concerning genetic testing and screening in public health[J]. Am J Med Genet C Semin Med Genet, 2004, 125C(1): 66-70. doi: 10.1002/ajmg.c.v125c:1
[117]	National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: genetic/familial high-risk assessment: breast, ovarian, and pancreatic (version 2. 2024)[EB/OL]. [2023-11-18]. https://www.nccn.org.
[118]	National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: genetic/familial high-risk assessment: colorectal (version 2. 2023)[EB/OL]. [2023-11-18]. https://www.nccn.org.
[119]	Risk reduction and screening of cancer in hereditary breast-ovarian cancer syndromes: ESMO Clinical Practice Guideline[J]. Ann Oncol, 2023, 34(1): 33-47. doi: 10.1016/j.annonc.2022.10.004
[120]	中国抗癌协会家族遗传性肿瘤专业委员会. 中国家族遗传性肿瘤临床诊疗专家共识(2021年版)(2)—家族遗传性卵巢癌[J]. 中国肿瘤临床, 2021, 48(24): 1243-1247.
	Family Genetic Oncology Professional Committee of China Anti-Cancer Association. Consensus of clinical diagnosis and treatment experts on familial hereditary tumors in China (2021 edition) (2)-familial hereditary ovarian cancer[J]. Chin J Clin Oncol, 2021, 48(24): 1243-1247.
[121]	中国医师协会妇产科医师分会妇科肿瘤学组, 中国初级卫生保健基金会妇科肿瘤专业委员会. Lynch综合征相关性子宫内膜癌筛查与防治中国专家共识(2023年版)[J]. 中国实用妇科与产科杂志, 2023, 39(1): 49-57.
	Gynecological Oncology Group of the Obstetricians and Gynecologists Branch of the Chinese Medical Association, Gynecological Oncology Professional Committee of the China Primary Health Care Foundation. Chinese expert consensus on screening, prevention and treatment of Lynch syndrome-related endometrial cancer (2023 edition)[J]. Chin J Pract Gynecol Obstet, 2023, 39(1): 49-57.
[122]	徐丛剑, 康玉. 实用妇科肿瘤遗传学[M]. 北京: 人民卫生出版社, 2019.
	XU C J, KANG Y. Practical Gynecological Tumor Genetics[M]. Beijing: People’s Medical Publishing House, 2019.
[123]	中国抗癌协会. 中国肿瘤整合诊治指南(CACA)[M]. 天津: 天津科学技术出版社, 2022.
	China Anti-Cancer Association. CACA guidelines for holistic integrative management of cancer[M]. Tianjin: Tianjin Science and Technology Press, 2022.
[124]	陆国辉, 张学. 遗传性肿瘤遗传咨询[M]. 北京: 北京大学医学出版社, 2021.
	LU G H, ZHANG X. Genetic counseling for hereditary tumors[M]. Beijing: Peking University Medical Press, 2021.

推荐强度	证据级别	描述
A	1a	同质RCT的系统评价
	1b	单个RCT
	1c	全或无病案系列
B	2q	同质队列研究评价
	2b	单个队列研究（包括低质量RCT，如随访率<80%）
	2c	结果研究，生态研究
	3a	同质病例对照研究的系统评价
	3b	单个病例对照研究
C	4	病例系统研究（包括低质量队列研究和病例对照研究）
D	5	基于经验且未经严格论证的专家意见