Lower cancer incidence in Amsterdam-I criteria families without mismatch repair deficiency: Familial colorectal cancer type X

Noralane Morey Lindor, Kari Rabe, Gloria M Petersen, Robert Haile, Graham Casey, John Baron, Steve Gallinger, Bharati Bapat, Melyssa Aronson, John Hopper, Jeremy Jass, Loic LeMarchand, John Grove, John Potter, Polly Newcomb, Jonathan P. Terdiman, Peggy Conrad, Gabriella Moslein, Richard Goldberg, Argyrios ZiogasHoda Anton-Culver, Mariza De Andrade, Kim Siegmund, Stephen N Thibodeau, Lisa Allyn Boardman, Daniela Seminara

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Abstract

Context: Approximately 60% of families that meet the Amsterdam-I criteria (AC-I) for hereditary nonpolyposis colorectal cancer (HNPCC) have a hereditary abnormality in a DNA mismatch repair (MMR) gene. Cancer incidence in AC-I families with MMR gene mutations is reported to be very high, but cancer incidence for individuals in AC-I families with no evidence of an MMR defect is unknown. Objective: To determine if cancer risks in AC-I families with no apparent deficiency in DNA MMR are different from cancer risks in AC-I families with DNA MMR abnormalities. Design, Setting, and Participants: Identification (1997-2001) of 161 AC-I pedigrees from multiple population- and clinic-based sources in North America and Germany, with families grouped into those with (group A) or without (group B) MMR deficiency by tumor testing. A total of 3422 relatives were included in the analyses. Main Outcome Measures: Cancer incidence in groups A and B (excluding the 3 affected members used to define each pedigree as AC-I) and computed age- and sex-adjusted standardized incidence ratios (SIRs) using Surveillance, Epidemiology, and End Results data. Results: Group A families from both population- and clinic-based series showed increased incidence of the HNPCC-related cancers. Group B families showed increased incidence only for colorectal cancer (SIR, 2.3; 95% confidence interval, 1.7-3.0) and to a lesser extent than group A (SIR, 6.1; 95% confidence interval, 5.2-7.2) (P<.001). Conclusions: Families who fulfill AC-I criteria but who have no evidence of a DNA MMR defect do not share the same cancer incidence as families with HNPCC-Lynch syndrome (ie, hereditary MMR deficiency). Relatives in such families have a lower incidence of colorectal cancer than those in families with HNPCC-Lynch syndrome, and incidence may not be increased for other cancers. These families should not be described or counseled as having HNPCC-Lynch syndrome. To facilitate distinguishing these entities, the designation of "familial colorectal cancer type X" is suggested to describe this type of familial aggregation of colorectal cancer.

Original languageEnglish (US)
Pages (from-to)1979-1985
Number of pages7
JournalJournal of the American Medical Association
Volume293
Issue number16
DOIs
StatePublished - Apr 27 2005

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Hereditary Nonpolyposis Colorectal Neoplasms
Colorectal Neoplasms
DNA Mismatch Repair
Incidence
Neoplasms
Pedigree
Turcot syndrome
Confidence Intervals
North America
Population
Genes
Germany
Epidemiology
Outcome Assessment (Health Care)
Mutation

ASJC Scopus subject areas

  • Medicine(all)

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Lower cancer incidence in Amsterdam-I criteria families without mismatch repair deficiency : Familial colorectal cancer type X. / Lindor, Noralane Morey; Rabe, Kari; Petersen, Gloria M; Haile, Robert; Casey, Graham; Baron, John; Gallinger, Steve; Bapat, Bharati; Aronson, Melyssa; Hopper, John; Jass, Jeremy; LeMarchand, Loic; Grove, John; Potter, John; Newcomb, Polly; Terdiman, Jonathan P.; Conrad, Peggy; Moslein, Gabriella; Goldberg, Richard; Ziogas, Argyrios; Anton-Culver, Hoda; De Andrade, Mariza; Siegmund, Kim; Thibodeau, Stephen N; Boardman, Lisa Allyn; Seminara, Daniela.

In: Journal of the American Medical Association, Vol. 293, No. 16, 27.04.2005, p. 1979-1985.

Research output: Contribution to journalArticle

Lindor, NM, Rabe, K, Petersen, GM, Haile, R, Casey, G, Baron, J, Gallinger, S, Bapat, B, Aronson, M, Hopper, J, Jass, J, LeMarchand, L, Grove, J, Potter, J, Newcomb, P, Terdiman, JP, Conrad, P, Moslein, G, Goldberg, R, Ziogas, A, Anton-Culver, H, De Andrade, M, Siegmund, K, Thibodeau, SN, Boardman, LA & Seminara, D 2005, 'Lower cancer incidence in Amsterdam-I criteria families without mismatch repair deficiency: Familial colorectal cancer type X', Journal of the American Medical Association, vol. 293, no. 16, pp. 1979-1985. https://doi.org/10.1001/jama.293.16.1979
Lindor, Noralane Morey ; Rabe, Kari ; Petersen, Gloria M ; Haile, Robert ; Casey, Graham ; Baron, John ; Gallinger, Steve ; Bapat, Bharati ; Aronson, Melyssa ; Hopper, John ; Jass, Jeremy ; LeMarchand, Loic ; Grove, John ; Potter, John ; Newcomb, Polly ; Terdiman, Jonathan P. ; Conrad, Peggy ; Moslein, Gabriella ; Goldberg, Richard ; Ziogas, Argyrios ; Anton-Culver, Hoda ; De Andrade, Mariza ; Siegmund, Kim ; Thibodeau, Stephen N ; Boardman, Lisa Allyn ; Seminara, Daniela. / Lower cancer incidence in Amsterdam-I criteria families without mismatch repair deficiency : Familial colorectal cancer type X. In: Journal of the American Medical Association. 2005 ; Vol. 293, No. 16. pp. 1979-1985.
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abstract = "Context: Approximately 60{\%} of families that meet the Amsterdam-I criteria (AC-I) for hereditary nonpolyposis colorectal cancer (HNPCC) have a hereditary abnormality in a DNA mismatch repair (MMR) gene. Cancer incidence in AC-I families with MMR gene mutations is reported to be very high, but cancer incidence for individuals in AC-I families with no evidence of an MMR defect is unknown. Objective: To determine if cancer risks in AC-I families with no apparent deficiency in DNA MMR are different from cancer risks in AC-I families with DNA MMR abnormalities. Design, Setting, and Participants: Identification (1997-2001) of 161 AC-I pedigrees from multiple population- and clinic-based sources in North America and Germany, with families grouped into those with (group A) or without (group B) MMR deficiency by tumor testing. A total of 3422 relatives were included in the analyses. Main Outcome Measures: Cancer incidence in groups A and B (excluding the 3 affected members used to define each pedigree as AC-I) and computed age- and sex-adjusted standardized incidence ratios (SIRs) using Surveillance, Epidemiology, and End Results data. Results: Group A families from both population- and clinic-based series showed increased incidence of the HNPCC-related cancers. Group B families showed increased incidence only for colorectal cancer (SIR, 2.3; 95{\%} confidence interval, 1.7-3.0) and to a lesser extent than group A (SIR, 6.1; 95{\%} confidence interval, 5.2-7.2) (P<.001). Conclusions: Families who fulfill AC-I criteria but who have no evidence of a DNA MMR defect do not share the same cancer incidence as families with HNPCC-Lynch syndrome (ie, hereditary MMR deficiency). Relatives in such families have a lower incidence of colorectal cancer than those in families with HNPCC-Lynch syndrome, and incidence may not be increased for other cancers. These families should not be described or counseled as having HNPCC-Lynch syndrome. To facilitate distinguishing these entities, the designation of {"}familial colorectal cancer type X{"} is suggested to describe this type of familial aggregation of colorectal cancer.",
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T1 - Lower cancer incidence in Amsterdam-I criteria families without mismatch repair deficiency

T2 - Familial colorectal cancer type X

AU - Lindor, Noralane Morey

AU - Rabe, Kari

AU - Petersen, Gloria M

AU - Haile, Robert

AU - Casey, Graham

AU - Baron, John

AU - Gallinger, Steve

AU - Bapat, Bharati

AU - Aronson, Melyssa

AU - Hopper, John

AU - Jass, Jeremy

AU - LeMarchand, Loic

AU - Grove, John

AU - Potter, John

AU - Newcomb, Polly

AU - Terdiman, Jonathan P.

AU - Conrad, Peggy

AU - Moslein, Gabriella

AU - Goldberg, Richard

AU - Ziogas, Argyrios

AU - Anton-Culver, Hoda

AU - De Andrade, Mariza

AU - Siegmund, Kim

AU - Thibodeau, Stephen N

AU - Boardman, Lisa Allyn

AU - Seminara, Daniela

PY - 2005/4/27

Y1 - 2005/4/27

N2 - Context: Approximately 60% of families that meet the Amsterdam-I criteria (AC-I) for hereditary nonpolyposis colorectal cancer (HNPCC) have a hereditary abnormality in a DNA mismatch repair (MMR) gene. Cancer incidence in AC-I families with MMR gene mutations is reported to be very high, but cancer incidence for individuals in AC-I families with no evidence of an MMR defect is unknown. Objective: To determine if cancer risks in AC-I families with no apparent deficiency in DNA MMR are different from cancer risks in AC-I families with DNA MMR abnormalities. Design, Setting, and Participants: Identification (1997-2001) of 161 AC-I pedigrees from multiple population- and clinic-based sources in North America and Germany, with families grouped into those with (group A) or without (group B) MMR deficiency by tumor testing. A total of 3422 relatives were included in the analyses. Main Outcome Measures: Cancer incidence in groups A and B (excluding the 3 affected members used to define each pedigree as AC-I) and computed age- and sex-adjusted standardized incidence ratios (SIRs) using Surveillance, Epidemiology, and End Results data. Results: Group A families from both population- and clinic-based series showed increased incidence of the HNPCC-related cancers. Group B families showed increased incidence only for colorectal cancer (SIR, 2.3; 95% confidence interval, 1.7-3.0) and to a lesser extent than group A (SIR, 6.1; 95% confidence interval, 5.2-7.2) (P<.001). Conclusions: Families who fulfill AC-I criteria but who have no evidence of a DNA MMR defect do not share the same cancer incidence as families with HNPCC-Lynch syndrome (ie, hereditary MMR deficiency). Relatives in such families have a lower incidence of colorectal cancer than those in families with HNPCC-Lynch syndrome, and incidence may not be increased for other cancers. These families should not be described or counseled as having HNPCC-Lynch syndrome. To facilitate distinguishing these entities, the designation of "familial colorectal cancer type X" is suggested to describe this type of familial aggregation of colorectal cancer.

AB - Context: Approximately 60% of families that meet the Amsterdam-I criteria (AC-I) for hereditary nonpolyposis colorectal cancer (HNPCC) have a hereditary abnormality in a DNA mismatch repair (MMR) gene. Cancer incidence in AC-I families with MMR gene mutations is reported to be very high, but cancer incidence for individuals in AC-I families with no evidence of an MMR defect is unknown. Objective: To determine if cancer risks in AC-I families with no apparent deficiency in DNA MMR are different from cancer risks in AC-I families with DNA MMR abnormalities. Design, Setting, and Participants: Identification (1997-2001) of 161 AC-I pedigrees from multiple population- and clinic-based sources in North America and Germany, with families grouped into those with (group A) or without (group B) MMR deficiency by tumor testing. A total of 3422 relatives were included in the analyses. Main Outcome Measures: Cancer incidence in groups A and B (excluding the 3 affected members used to define each pedigree as AC-I) and computed age- and sex-adjusted standardized incidence ratios (SIRs) using Surveillance, Epidemiology, and End Results data. Results: Group A families from both population- and clinic-based series showed increased incidence of the HNPCC-related cancers. Group B families showed increased incidence only for colorectal cancer (SIR, 2.3; 95% confidence interval, 1.7-3.0) and to a lesser extent than group A (SIR, 6.1; 95% confidence interval, 5.2-7.2) (P<.001). Conclusions: Families who fulfill AC-I criteria but who have no evidence of a DNA MMR defect do not share the same cancer incidence as families with HNPCC-Lynch syndrome (ie, hereditary MMR deficiency). Relatives in such families have a lower incidence of colorectal cancer than those in families with HNPCC-Lynch syndrome, and incidence may not be increased for other cancers. These families should not be described or counseled as having HNPCC-Lynch syndrome. To facilitate distinguishing these entities, the designation of "familial colorectal cancer type X" is suggested to describe this type of familial aggregation of colorectal cancer.

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