Survival by colon cancer stage and screening interval in Lynch syndrome: a prospective Lynch syndrome database report

Dominguez‐Valentin, Mev; Seppälä, Toni T.; Sampson, Julian R.; Macrae, Finlay; Winship, Ingrid; Evans, D. Gareth; Scott, Rodney J.; Burn, John; Möslein, Gabriela; Bernstein, Inge; Pylvänäinen, Kirsi; Renkonen–Sinisalo, Laura; Lepistö, Anna; Lindblom, Annika; Plazzer, John Paul; Tjandra, Douglas; Thomas, Huw; Green, Kate; Lalloo, Fiona; Crosbie, Emma J.; Hill, James A.; Capellà, Gabriel; Pineda, Marta; Navarro, Matilde; Vidal, J; Rønlund, Karina; Nielsen, Randi Thyregaard; Yilmaz, Mette Karen; Elvang, Louise Laurberg; Katz, Lior H.; Nielsen, Maartje; Broeke, Sanne W. ten; Nakken, Sigve; Hovig, Eivind; Sunde, Lone; Kloor, Matthias; Doeberitz, Magnus von Knebel; Ahadova, Aysel; Lindor, Noralane M.; Steinke‐Lange, Verena; Holinski‐Feder, Elke; Mecklin∥, Jukka–Pekka; Møller, Pål

doi:10.1186/s13053-019-0127-3

Cited by 33 publications

(37 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition to the four descriptive reports described above, three hypothesis-testing papers have been published: CRC incidence related to the interval between colonoscopies [16], clinic-pathological stage of colon cancer related to time since last colonoscopy [17] and survival after colon cancer related to time since last colonoscopy [18].…”

Section: Methodsmentioning

confidence: 99%

The Prospective Lynch Syndrome Database reports enable evidence-based personal precision health care

Møller

2020

Hered Cancer Clin Pract

Self Cite

View full text Add to dashboard Cite

The aims of the Prospective Lynch Syndrome Database (PLSD) are to provide empirical prospectively observed data on the incidences of cancer in different organs, survival following cancer and the effects of interventions in carriers of pathogenic variants of the mismatch repair genes (path_MMR) categorized by age, gene and gender. Although PLSD is assumption-free, as with any study the ascertainment procedures used to identify the study cohort will introduce selection biases which have to be declared and considered in detail in order to provide robust and valid results. This paper provides a commentary on the methods used and considers how results from the PLSD reports should be interpreted. A number of the results from PLSD were novel and some in conflict with previous assumptions. Notably, colonoscopic surveillance did not prevent colo-rectal cancer, survival after colo-rectal, endometrial and ovarian cancer was good, no survival gain was observed with more frequent colonoscopy, new causes of cancer-related death were observed in survivors of first cancers due to later cancers in other organs, variants in the different MMR genes caused distinct multi-cancer syndromes characterized by different penetrance and phenotypes. The www.PLSD.eu website together with the InSiGHT database website (https://www.insight-group.org/variants/databases/) now facilitate evidence-based personalized precision health care for individual carriers at increased risk of cancer. The arguments are summarized in a final discussion on how to conceptualize current knowledge for the different practical purposes of treating cancers, genetic counselling and prevention, and for understanding /research on carcinogenetic mechanisms.

show abstract

Section: Methodsmentioning

confidence: 99%

The Prospective Lynch Syndrome Database reports enable evidence-based personal precision health care

Møller

2020

Hered Cancer Clin Pract

Self Cite

View full text Add to dashboard Cite

show abstract

“…While 312 of the 425 carriers (73.4%) had a single cancer, 113 (26.6%) had more than one CRC (42 (9.9%) synchronous CRC and 71 (16.7%) metachronous CRC). The mean lapse between the first and the second CRC was 10.5 years (range [5][6][7][8][9][10][11][12][13][14][15][16][17][18]. No differences regarding metachronous and synchronous CRC were evident between MLH1 and MSH2 carriers (p > 0.…”

Section: Resultsmentioning

confidence: 89%

“…ES extended surgery,2 SS segmental surgery,3 mCRC metachronous colorectal cancer,4 Ams families which meet Amsterdam criteria,5 LS Lynch syndrome patients,6 n.r. not reported,7 extended right hemicolectomy is included in extended surgery,8 only considered when initial tumor is right-sided tumor,9 15 years overall survival,10 25 years overall survival.Cancers 2020, 12, 3419…”

mentioning

confidence: 99%

Assessing Effectiveness of Colonic and Gynecological Risk Reducing Surgery in Lynch Syndrome Individuals

Dueñas

Navarro

Teulé

et al. 2020

Cancers

Self Cite

View full text Add to dashboard Cite

Background: Colorectal (CRC) and endometrial cancer (EC) are the most common types of cancer in Lynch syndrome (LS). Risk reducing surgeries (RRS) might impact cancer incidence and mortality. Our objectives were to evaluate cumulative incidences of CRC, gynecological cancer and all-cause mortality after RRS in LS individuals. Methods: Retrospective analysis of 976 LS carriers from a single-institution registry. Primary endpoints were cumulative incidence at 75 years of cancer (metachronous CRC in 425 individuals; EC and ovarian cancer (OC) in 531 individuals) and all-cause mortality cumulative incidence, comparing extended (ES) vs. segmental surgery (SS) in the CRC cohort and risk reducing gynecological surgery (RRGS) vs. surveillance in the gynecological cohort. Results: Cumulative incidence at 75 years of metachronous CRC was 12.5% vs. 44.7% (p = 0.04) and all-cause mortality cumulative incidence was 38.6% vs. 55.3% (p = 0.31), for ES and SS, respectively. Cumulative, incidence at 75 years was 11.2% vs. 46.3% for EC (p = 0.001) and 0% vs. 12.7% for OC (p N/A) and all-cause mortality cumulative incidence was 0% vs. 52.7% (p N/A), for RRGS vs. surveillance, respectively. Conclusions: RRS in LS reduces the incidence of metachronous CRC and gynecological neoplasms, also indicating a reduction in all-cause mortality cumulative incidence in females undergoing RRGS.

show abstract

“…Although LS and FCCTX are different entities, they share analogous pedigree features, as found in the current study. The surveillance guidelines for LS are well established ( 31 – 33 ) and are aimed at the diagnosis of colorectal adenomas, early CRC, and other LS-related cancers. Recent clinical guidelines suggest colonoscopy at least once every 2 years, beginning between age 20 and 25 years ( 32 ).…”

Section: Discussionmentioning

confidence: 99%

“…Recent clinical guidelines suggest colonoscopy at least once every 2 years, beginning between age 20 and 25 years ( 32 ). The Prospective LS Database reported that colonoscopy performed in intervals of <3 years is beneficial for the follow-up of MMR variant carriers ( 33 , 34 ). Primary prevention screening colonoscopy in asymptomatic family members significantly decreased the risk of CRC in FCCTX ( 35 ).…”

Section: Discussionmentioning

confidence: 99%

Comparison Between Familial Colorectal Cancer Type X and Lynch Syndrome: Molecular, Clinical, and Pathological Characteristics and Pedigrees

Liu

Zhang

et al. 2020

Front. Oncol.

View full text Add to dashboard Cite

Objective This study aimed to compare the molecular, clinical, and pathological characteristics and pedigrees of familial colorectal cancer type X (FCCTX) with those of Lynch syndrome (LS) to provide a theoretical basis for the management of FCCTX. Methods Overall, 46 cases of FCCTX and 47 LS probands and affected families were enrolled between June 2008 and September 2018 for this study. Multigene cancer panel tests that included 139 genes were performed for all patients, and variants in each group were described. The clinical, pathological, and pedigree characteristics were also compared between the two groups. Results In total, 42 variants were detected in 27 (58.7%) cases in the FCCTX group, with BRCA1 , BRCA2 , POLE , POLD1 , ATR , and ATM being the most frequently mutated genes. The mean onset age of colorectal cancer (CRC) was significantly older in the FCCTX group than in the LS group (53.57 ± 12.88 years vs. 44.36 ± 11.26 years, t = −9.204, p < 0.001). The proportion of patients with rectal cancer was also higher in the FCCTX group than in the LS group [43.5% (20/46) vs. 10.6% (5/47), χ 2 = 12.823, p = 0.005]. Within a median follow-up time of 53.9 ± 37.0 months, the proportion of patients who developed metachronous CRC was significantly higher in the LS group than in the FCCTX group [34.0% (16/47) vs. 13.0% (6/46), χ 2 = 5.676, p = 0.017]. When comparing pedigrees, older age at cancer onset and rectal cancer clustering were observed in the FCCTX families. A higher prevalence in male patients was also observed in the FCCTX families. Conclusion FCCTX is an entity distinct from LS, but its genetic etiology remains unknown. A larger multigene panel would be recommended for determining the underlying pathogenic variants. Considering the pathology and moderate penetrance of the CRC link to FCCTX, less stringent surgical treatments and colonoscopy surveillance would be preferable. Rectum preference is a typical feature of FCCTX. Colonoscopy surveillance in FCCTX families could be less intensive, and more attention should be given to male members.

show abstract

Survival by colon cancer stage and screening interval in Lynch syndrome: a prospective Lynch syndrome database report

Cited by 33 publications

References 13 publications

The Prospective Lynch Syndrome Database reports enable evidence-based personal precision health care

The Prospective Lynch Syndrome Database reports enable evidence-based personal precision health care

Assessing Effectiveness of Colonic and Gynecological Risk Reducing Surgery in Lynch Syndrome Individuals

Comparison Between Familial Colorectal Cancer Type X and Lynch Syndrome: Molecular, Clinical, and Pathological Characteristics and Pedigrees

Contact Info

Product

Resources

About