fe48e7629ed4cb59e24a1a3d9c890edc 284130.pdf 49741e7b6afb3c67aa0f46c835cf5d1dce320808 284130.pdf 204de5e99390624a96acf589cb5f1c7884ca2cd5f59dee75406fce3b5a760250 284130.pdf Title: Risk of Cancer in Family Members of Patients with Lynch-Like Syndrome Subject: Lynch syndrome (LS) is a common cause of hereditary colorectal cancer (CRC). Some CRC patients develop mismatch repair deficiency without germline pathogenic mutation, known as Lynch-like syndrome (LLS). We compared the risk of CRC in first-degree relatives (FDRs) in LLS and LS patients. LLS was diagnosed when tumors showed immunohistochemical loss of MSH2, MSH6, and PMS2; or loss of MLH1 with BRAF wild type; and/or no MLH1 methylation and absence of pathogenic mutation in these genes. CRC and other LS-related neoplasms were followed in patients diagnosed with LS and LLS and among their FDRs. Standardized incidence ratios (SIRs) were calculated for CRC and other neoplasms associated with LS among FDRs of LS and LLS patients. In total, 205 LS (1205 FDRs) and 131 LLS families (698 FDRs) had complete pedigrees. FDRs of patients with LLS had a high incidence of CRC (SIR, 2.08; 95% confidence interval (CI), 1.56–2.71), which was significantly lower than that in FDRs of patients with LS (SIR, 4.25; 95% CI, 3.67–4.90; p < 0.001). The risk of developing other neoplasms associated with LS also increased among FDR of LLS patients (SIR, 2.04; 95% CI, 1.44–2.80) but was lower than that among FDR of patients with LS (SIR, 5.01, 95% CI, 4.26–5.84; p < 0.001). FDRs with LLS have an increased risk of developing CRC as well as LS-related neoplasms, although this risk is lower than that of families with LS. Thus, their management should take into account this increased risk. Keywords: colorectal cancer; risk; genetic; surveillance Author: María Dolores Picó, Ana Beatriz Sánchez-Heras, Adela Castillejo, Mar Giner-Calabuig, Miren Alustiza, Ariadna Sánchez, Leticia Moreira, María Pellise, Antoni Castells, Gemma Llort, Carmen Yagüe, Teresa Ramon y Cajal, Alexandra Gisbert-Beamud, Joaquin Cubiella, Laura Rivas, Maite Herraiz, Catalina Garau, Inmaculada Salces, Marta Carrillo-Palau, Luis Bujanda, Adriá López-Fernández, Cristina Alvarez-Urturi, María Jesús López, Cristina Alenda, Pedro Zapater, Francisco Javier Lacueva, Francesc Balaguer, Jose-Luis Soto, Óscar Murcia and Rodrigo Jover Creator: LaTeX with hyperref package Producer: pdfTeX-1.40.18 CreationDate: Sun Aug 9 13:21:18 2020 CEST ModDate: Sun Aug 9 13:21:18 2020 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 12 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1426473 bytes Optimized: no PDF version: 1.5 name type encoding emb sub uni object ID 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ぐちぴどづのぴびぜ〴ぜ〰ちのつぜ〴ぜ〰いちぴちぜ〴ぜ〰ぃはぬぬづっぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㈩‾㸊⡜㌷㙜㌷㝜〰きこぉ〬ぜ〴ぜ〰ぉえぃぜ〴ぜ〰こぴちどのどので〬ぜ〴ぜ〰ちのつぜ〴ぜ〰いづぴづっぴどはのぜ〴ぜ〰はてぜ〴ぜ〰ぇづひねぬどのづぜ〴ぜ〰きふぴちぴどはのびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㌩‾㸊⡜㌷㙜㌷㝜〰ぃちぬっふぬちぴどはのぜ〴ぜ〰はてぜ〴ぜ〰こぴちのつちひつどぺづつぜ〴ぜ〰ぉのっどつづのっづぜ〴ぜ〰げちぴどはぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㐩‾㸊⡜㌷㙜㌷㝜〰こぴちぴどびぴどっちぬぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: きこぉ〬ぜ〴ぜ〰ぉえぃぜ〴ぜ〰こぴちどのどので〬ぜ〴ぜ〰ちのつぜ〴ぜ〰いづぴづっぴどはのぜ〴ぜ〰はてぜ〴ぜ〰ぇづひねぬどのづぜ〴ぜ〰きふぴちぴどはのびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㌩‾㸊⡜㌷㙜㌷㝜〰ぃちぬっふぬちぴどはのぜ〴ぜ〰はてぜ〴ぜ〰こぴちのつちひつどぺづつぜ〴ぜ〰ぉのっどつづのっづぜ〴ぜ〰げちぴどはぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㐩‾㸊⡜㌷㙜㌷㝜〰こぴちぴどびぴどっちぬぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: ぃちぬっふぬちぴどはのぜ〴ぜ〰はてぜ〴ぜ〰こぴちのつちひつどぺづつぜ〴ぜ〰ぉのっどつづのっづぜ〴ぜ〰げちぴどはぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㐩‾㸊⡜㌷㙜㌷㝜〰こぴちぴどびぴどっちぬぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: こぴちぴどびぴどっちぬぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: げづびふぬぴびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮ㄩ‾㸊⡜㌷㙜㌷㝜〰ぃぬどのどっちぬぜ〴ぜ〰ちのつぜ〴ぜ〰ぐちぴとはぬはでべぜ〴ぜ〰いどててづひづのっづびぜ〴ぜ〰どのぜ〴ぜ〰ぃげぃぜ〴ぜ〰ぢづぴぷづづのぜ〴ぜ〰がこぜ〴ぜ〰ちのつぜ〴ぜ〰ががこぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㈩‾㸊⡜㌷㙜㌷㝜〰げどびにぜ〴ぜ〰はてぜ〴ぜ〰ぃげぃぜ〴ぜ〰どのぜ〴ぜ〰ういげびぜ〴ぜ〰はてぜ〴ぜ〰がこぜ〴ぜ〰ちのつぜ〴ぜ〰ががこぜ〴ぜ〰ぐちぴどづのぴびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Children: Item: Title: ぃぬどのどっちぬぜ〴ぜ〰ちのつぜ〴ぜ〰ぐちぴとはぬはでべぜ〴ぜ〰いどててづひづのっづびぜ〴ぜ〰どのぜ〴ぜ〰ぃげぃぜ〴ぜ〰ぢづぴぷづづのぜ〴ぜ〰がこぜ〴ぜ〰ちのつぜ〴ぜ〰ががこぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㈩‾㸊⡜㌷㙜㌷㝜〰げどびにぜ〴ぜ〰はてぜ〴ぜ〰ぃげぃぜ〴ぜ〰どのぜ〴ぜ〰ういげびぜ〴ぜ〰はてぜ〴ぜ〰がこぜ〴ぜ〰ちのつぜ〴ぜ〰ががこぜ〴ぜ〰ぐちぴどづのぴびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Item: Title: げどびにぜ〴ぜ〰はてぜ〴ぜ〰ぃげぃぜ〴ぜ〰どのぜ〴ぜ〰ういげびぜ〴ぜ〰はてぜ〴ぜ〰がこぜ〴ぜ〰ちのつぜ〴ぜ〰ががこぜ〴ぜ〰ぐちぴどづのぴびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Item: Title: いどびっふびびどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸵ Item: Title: ぃはのっぬふびどはのびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸵ Item: Title: げづてづひづのっづび Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: FATHTC+Rpxr FontSubset: true FirstChar: 11 LastChar: 61 FontDescriptor: FontName: FATHTC+Rpxr Flags: Symbolic FontBBox: -40, -283, 904, 728 FontFile: true Font: BaseFont: CRUZTT+VnURWPalladioL-Italic FontSubset: true FirstChar: 189 LastChar: 189 FontDescriptor: FontName: CRUZTT+VnURWPalladioL-Italic Flags: Symbolic FontBBox: -170, -305, 1010, 941 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: QLBIEB+URWPalladioL-BoldItal FontSubset: true FirstChar: 110 LastChar: 112 FontDescriptor: FontName: 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