Data instructions

In order to be included for the IMRC study on penetrance, data is needed on family history of cancer and who is and is not a mutation carrier.  The preferred format for sending data is an excel file, or database containing the data listed below.  Alternatively, if this is not possible, pedigrees containing as much of this data as possible is required.

Note: do not provide identifying information including names, address, or contact details.

Before sending data please email the study coordinator, Jeanette Reece (This email address is being protected from spambots. You need JavaScript enabled to view it.This email address is being protected from spambots. You need JavaScript enabled to view it. email address is being protected from spambots. You need JavaScript enabled to view it. 
), for instructions.

 

 

Progress of submission of Lynch syndrome families

Data submissions as at 1st July, 2017: 

      CONSORTIUMS    

   No. submitted   

  TOTAL

       No. families submitted     

   TARGET

        No. families    

57  6054 8800
  (136,900 individuals)  

   

 

Data dictionary:

 

"Comprehensive"                 

- consists of 3 tables; Demographics, Cancer and CRC_Treatment

 

(see below for "Minimum requirements")

Demographics data table (one row per person; multiple rows per family)

Variable Description Data type Allowable values
 CENTER_NAME What is the name of your center or clinic? Text  
 GENETIC_MMR_TEST_FAM_HX
Ascertainment: Was the MMR mutation testing done on the first person identified as the MMR mutation carrier (proband) because of a family history of cancer? 
  0  No  (population-based)
  1  Yes (clinic-based)
  9  Unknown
Number
Range:
0-1 or 9
 DATE_MMR_TEST_PERSON  
What is the known or approximate date of the person's MMR genetic test (if tested)? (9999=unknown year; 99=unknown month; 99=unknown date)
String Format: YYYYMMDD
 FAMILY_ID What is the ID number of the family? String  
 PERSON_ID What is the ID number of the person? This must be an ID that is unique to your data. String  
 MOTHER_ID What is the ID number of the mother? String  
 FATHER_ID What is the ID number of the father? String  
 TWIN_ID

If the person has a twin, what is their twin’s ID number? Leave blank if they do not have a twin.

String  
 TWIN_TYPE
What type of twin are they? Leave blank if they do not have a twin.
 
  1  Monozygous (identical)
  2  Dizygous (non-identical)
  9  Unknown
Number
Range:
1-2 or 9
 PROBAND_FLAG
Was this person the first in the family identified as a MMR mutation carrier?
 
  0  No
  1  Yes
  9  Unknown
Number
Range:
0-1 or 9
 
 SEX
What is the gender of the person?
 
  1  Male
  2  Female
  9  Unknown
Number
Range:
1-2 or 9
 
 DOB
What is their known or approximate date of birth?
(9999=unknown year; 99=unknown month; 99=unknown date)
String Format: YYYYMMDD
 *BASELINE_AGE At what age was the person recruited to the study? Number Range: 0-130 or 999
 VS
Is the person known to be alive?
  1  Alive
  2  Dead
  9  Unknown
Number
Range:
1-2 or 9
 
 LIVE_AGE
If alive, what is the person's last known age?
(999=unknown)
Number
Range:
0-130 or 999
 LIVEDATE
What is the most recent date a subject is known to be living? (9999=unknown year; 99=unknown month; 99=unknown date)
String  Format: YYYYMMDD
 AGE_DEATH
If deceased, at what age were they when they died?
(999=unknown)
Number 
Range:
0-130 or 999
 DTHDATE What is their date of death? (9999=unknown year; 99=unknown month; 99=unknown date) String Format: YYYYMMDD
 RACE

What is their race/ethnicity?

Caucasian
2

African American/Black (except African; except Caribbean)

3

Latino, Hispanic, Mexican American, Mexican, Cuban, Puerto Rican

4 Japanese
5 Chinese
6 Filipino/Malay/Indonesian
7 Korean
8

South East Asian (except Chinese) (such as Vietnamese, Laotian, Thai, Hmong, Kampuchean)

9 South Asian (such as Indian, Pakistani, Sri Lankan)
10 Native American, Inuit, Aleutian, First Nations Person
11

Polynesian (such as Hawaiian, Maor, Samoan, Tongan, Tahitian, Cook Islander)

12 Micronesian
13 Australian Aboriginal
14 Melanesian (such as Fijian, New Guinean)
15

Caribbean Black (such as Jamaican, Trinidadian, Tobagonian)

16

Central/South American (such as Costa Rican, Salvadorian, Columbian,  Brazilian, Black African)

17 Black African
18 North African (such as Egyptian, Algerian, Moroccan)
19 Middle Eastern (such as Iranian, Lebanese, Kuwaiti, Saudi)
98 Other
99 Unknown
Number
Range:
1-19 or 99
 RACE_OTHER_TXT

Other race (text)?

Text  
 COB

In which country were they born?                                       http://seer.cancer.gov/archive/manuals/AppendB.pdf

String
Range:
000-750 or 999
 COB_TXT

In which country were they born (text)?

Text  
 MMR_GENE

Which MMR gene is mutated in the family?

  1   MLH1
  2   MSH2
  3   MSH6
  4   PMS2
  5   EPCAM
  9   Unknown
Number
Range:
1-6 or 9
 MMR_STATUS
What is their mutation status?
 
 -1  Not tested
  0  Non-carrier
  1  Carrier - heterozygous
  2  Carrier - homozygous
  9  Test result - inconclusive
Number
Range:
0-1 or 9
 MMR_VARIANT_NAME What is the description of the mutation (use LOVD nomenclature where possible)? Text  
 *COLONOSCOPY
Has the person ever had a colonoscopy?
 
  0  No
  1  Yes
  8  Not asked
  9  Unknown
Number
Range:
0-1 or 8-9
 
 *AGE_FIRST_COLONOSCOPY
How old was the person when they first had a colonoscopy? (999=unknown)
Number
Range:
0-130 or 999
 *AGE_LAST_COLONOSCOPY
How many separate colonoscopies has the person had? (999=unknown)
Number
Range:
0-130 or 999
 *COLONOSCOPY_NO
How old was the person when they last had a colonoscopy?(999=unknown)
Number
Range:
0-130 or 999
 POLYPECTOMY
Has the person ever had a polypectomy?
 
  0  No
  1  Yes
  9  Unknown
Number
Range:
0-1 or 9
 POLYP_TYPE1

Type of isolated first polyp #1 ?

  1  TA (tubular adenoma)
  2  TV (tubulovillous)
  3  VA (villous)
  4  SA (serrated adenoma)
  5  HP (hyperplastic polyp)
  6  Other
  7  Adenomatous, type unspecified
  8  Mixed Polyp
  9  Unknown
Number
Range:
1-9
 AGE_FIRST_POLYPECTOMY
If yes, what was their age when they had their first polypectomy? (999=unknown)
Number
Range:
0-130 or 999
 HYSTERECTOMY
Has the person ever had their uterus removed (hysterectomy)?
 
  0  No
  1  Yes
  9  Unknown
Number
Range:
0-1 or 9
 
 AGE_HYSTERECTOMY
If yes, what was their age when they had their hysterectomy? (999=unknown)
Number
Range:
0-130 or 999
 OOPHORECTOMY
Has the person ever had both their ovaries removed (oophorectomy)?
 
  0  No
  1  Yes
  9  Unknown
Number
Range:
0-1 or 9
 AGE_OOPHORECTOMY
If yes, what was their age when they had their oophorectomy? (999=unknown)
Number
Range:
0-130 or 999
 MASTECTOMY
Has the person ever had one of their breasts removed (mastectomy)?
 
  0  No
  1  Yes
  9  Unknown
Number 
Range:
0-1 or 9
 AGE_MASTECTOMY
If yes, what was their age when they had their oophorectomy? (999=unknown)
Number
Range:
0-130 or 999
 AFFECTED
Is the person affected with cancer?
 
  0  No
  1  Yes
  9  Unknown
Number
Range:
0-1 or 9

 *Additional variables added on 3rd March, 2016

  

Cancer data table (one row per primary cancer: multiple rows per person)

Variable Description Data type  Allowable values 
 CENTER_NAME What is the name of your center or clinic? Text  
 FAMILY_ID What is the ID of the family? String  
 PERSON_ID What is the ID of the person? This must be an ID that is unique to your data. String  
 TUMOR_NO

What is the ID of the primary cancer? This must be an ID that is unique to the individual.

Number

 
 TUMOR_SITE What is the site of the primary cancer? Use ICD-0 where possible. http://apps.who.int/classifications/icd10/browse/2010/en#/II Text

Range: C00.0-C97.0

 HISTOLOGY

First four digits of the ICD-0-3 morphology code which designates the histologic type of this tumor.

  8000   No specific histologic type information
  8001 to 9989    Range
  72680   Keratocanthoma

Number

Range: 8000-9989 or 72860

 BEHAVIOR

ICD-0-3 fifth digit behavior code (Coding based on SEER, NAACCR and AcoS guidelines.

   0   Benign
1   Uncertain; Low malignant potential; borderline
2   Carcinoma in situ
3   Malignant (invasive)
6   Malignant (metastatic site)
9   Malignant (uncertain whether primary or metastatic)

Number

Range:  0-3

 DXAGE

What is the age at diagnosis? (999=unknown)

Number

Range:
0-130 or 999
 DXDATE
What is the known or approximate date of diagnosis? (9999=unknown year; 99=unknown month; 99=unknown date)
String
Format: YYYYMMDD
 DXSRC

What is the source of information on the cancer diagnosis?

 1  Pathology review or pathology report 
 2  Hospital or clinic record
 3  Cancer registry
 4  Death certificate
 5  Report by the person
 6  Report by a relative or spouse of the person
 7  Other
 9  Unknown

Number

Range:
0-1 or 9
 DXSRC_OTHER

Other source, specify (eg. specialized genealogy)

Text

 

 

 

Treatment data table (one row per primary cancer: multiple rows per person)

Variable Description Data type Allowable values
 CENTER_NAME What is the name of your center or clinic? Text  
 FAMILY_ID What is the ID of the family? String  
 PERSON_ID What is the ID of the person? This must be an ID that is unique to your data. String  
 TUMOR_NO

What is the ID of the primary cancer? This must be an ID that is unique to the individual.

Number   
 CRC_T

Tumor stage at baseline (0-4)

  0 Carcinoma in situ/TIS
  1 Tumor invades submucosa
  2 Tumor invades muscularis propria
  3

Tumor invades through muscularis propria into submucosa or into non peritonealised pericolic or perirectal tissues

  4

Tumor directly invades other organs/structures/perforates visceral peritoneum

  9 Unknown
Number
Range:
0-4 or 9
 CRC_N

Nodal stage at baseline (0-2)

  0 No regional lymph node metastasis
  1 Metastasis in 1 to 3 regional lymph nodes
  2 Metastasis in 4 or more regional lymph nodes
  9 Unknown
Number
Range:
0-2 or 9
 CRC_M

Metastasis stage at baseline (0-1)

  0 No distant metastasis
  1 Distant metastasis is present
  9 Unknown
Number
Range:
0-1 or 9
 CRC_TNM

TNM stage of tumor

 1 I
2 II
3 III
4 IV
0 In-situ lesions
9 Unknown
Number
Range:
0-4 or 9
 CRC_SURG

Was surgical treatment performed for the primary colorectal cancer?

  0 No    
  1 Yes    
  9 Unknown    

Number

Range:
0-1 or 9

 CRC_SURG_DATE

What is the date of the first resection? (9999=unknown year; 99=unknown month; 99=unknown date)

String Format: YYYYMMDD 

 CRC_SURG_TYPE

Type of surgical treatment

 2   Local tumor destruction, i.e. laser, electrocautery
 3

  Local surgical excision with specimen - i.e. trans anal excision, polypectomy, snare

 4   Right Hemi colectomy
 5   Left Hemi colectomy
 6   Hemi colectomy side not specified: not total
 7   Low Anterior resection
 8   Total Colectomy
 9   Total Proctectomy
10   Total Proctocolectomy
11   Abdominoperineal resection
12   Segmental / Wedge / Partial Resection NOS
77   Other surgery
Number Range:
2-12 or 77

 CRC_SURG_OTHER

Surgery performed (other), specify

Text  
 CRC_CHEMO

Was chemotherapy treatment performed for the primary colorectal cancer?

  0   No
  1   Yes
  9   Unknown
Number
Range:
0-1 or 9
 
 CRC_CHEMO_METHOD

Method of chemotherapy applied for treatment of the primary colorectal cancer:

  1 Adjuvant
  2 Palliative
  3 Psuedo Adjuvant
  4 Neo Adjuvant (pre-operative)
  9 Unknown
Number
Range:
1-4 or 9
 CRC_RAD

Was radiation treatment performed for the primary colorectal cancer?

  0 No  
  1 Yes  
  9 Unknown  

Number

Range:
0-1 or 9
 CRC_RAD_METHOD

Method of radiotherapy for the primary colorectal cancer:

  1 Adjuvant  
  2 Palliative  
  3 Psuedo Adjuvant  
  4 Neo Adjuvant  
  9 Unknown  

Number

Range:
1-4 or 9

 

----------------------------------------------------------------------------------------------------- 

 

Data dictionary: "Minimum requirements"; 1 table

(add additional columns for second and subsequent cancers)

Variable Description Data type Allowable values
 CENTER_NAME What is the name of your center or clinic? Text  
 GENETIC_MMR_TEST_FAM_HX
Ascertainment: Was the MMR mutation testing done on the first person identified as the MMR mutation carrier (proband) because of a family history of cancer? 
  0  No  (population-based)
  1  Yes (clinic-based)
  9  Unknown
Number
Range:
0-1 or 9
 FAMILY_ID What is the ID number of the family? String  
 PERSON_ID What is the ID number of the person? This must be an ID that is unique to your data. String  
 MOTHER_ID What is the ID number of the mother? String  
 FATHER_ID What is the ID number of the father? String  
*TWIN_ID

If the person has a twin, what is their twin’s ID number? Leave blank if they do not have a twin.

String  
*TWIN_TYPE
What type of twin are they? Leave blank if they do not have a twin.
 
  1  Monozygous (identical)
  2  Dizygous (non-identical)
  9  Unknown
Number
Range:
1-2 or 9
 PROBAND_FLAG
Was this person the first in the family identified as a MMR mutation carrier?
 
  0  No
  1  Yes
  9  Unknown
Number
Range:
0-1 or 9
 
 SEX
What is the gender of the person?
 
  1  Male
  2  Female
  9  Unknown
Number
Range:
1-2 or 9
 
 BASELINE_AGE At what age was the person recruited to the study? Number Range: 0-130 or 999
 LAST_AGE
If alive, what is the person's last known age? If deceased, what was the person's age at death (999=unknown)?
Number 
Range:
0-130 or 999
 MMR_GENE

Which MMR gene is mutated in the family?

  1   MLH1
  2   MSH2
  3   MSH6
  4   PMS2
  5   EPCAM
  9   Unknown
Number
Range:
1-6 or 9
 MMR_STATUS
What is their mutation status?
 
 -1  Not tested
  0  Non-carrier
  1  Carrier - heterozygous
  2  Carrier - homozygous
  9  Test result - inconclusive
Number
Range:
0-1 or 9
 MMR_VARIANT_NAME What is the description of the mutation (use LOVD nomenclature where possible)? Text  
 AFFECTED
Is the person affected with cancer?
 
  0  No
  1  Yes
  9  Unknown
Number
Range:
0-1 or 9
 
 TUMOR_NO
What is the ID of the primary cancer?
Number
 TUMOR_SITE
What is the location of the primary cancer? Use ICD-O nomenclature where possible http://seer.cancer.gov/icd-o-3/sitetype.icdo3.d20150918.pdf
Text
Range:
C00.0-C97.0

 BEHAVIOR

ICD-0-3 fifth digit behavior code (Coding based on SEER, NAACCR and AcoS guidelines.

   0   Benign
1   Uncertain; Low malignant potential; borderline
2   Carcinoma in situ
3   Malignant (invasive)
6   Malignant (metastatic site)
9   Malignant (uncertain whether primary or metastatic)

Number

Range:  0-3

 DXAGE

What is the age at diagnosis? (999=unknown)

Number

Range:
0-130 or 999
*POLYPECTOMY
Has the person ever had a polypectomy?
 
  0  No
  1  Yes
  9  Unknown
Number
Range:
0-1 or 9
 
*AGE_FIRST_POLYPECTOMY
If yes, what was their age when they had their first polypectomy? (999=unknown)
Number
Range:
0-130 or 999
*HYSTERECTOMY
Has the person ever had their uterus removed (hysterectomy)?
 
  0  No
  1  Yes
  9  Unknown
Number
Range:
0-1 or 9
 
*AGE_HYSTERECTOMY
If yes, what was their age when they had their hysterectomy? (999=unknown)
Number
Range:
0-130 or 999
*OOPHORECTOMY
Has the person ever had both their ovaries removed (oophorectomy)?
 
  0  No
  1  Yes
  9  Unknown
Number
Range:
0-1 or 9
*AGE_OOPHORECTOMY
If yes, what was their age when they had their oophorectomy? (999=unknown)
Number
Range:
0-130 or 999
*MASTECTOMY
Has the person ever had one of their breasts removed (mastectomy)?
 
  0  No
  1  Yes
  9  Unknown
Number 
Range:
0-1 or 9
*AGE_MASTECTOMY
If yes, what was their age when they had their oophorectomy? (999=unknown)
Number
Range:
0-130 or 999

 *Not essential

Number of Lynch syndrome families and individuals by cancer status by continent that can be contributed by the International Mismatch Repair Consortium.

  Total Austral-asia Europe North America Asia South America Africa
Centres  59  11  18  20  5  4  1
Families  8863  1035  4724  2368  541  115  80
MLH1 
 3384  326  1979  756  222  61  40
MSH2 
 3988  440  2098  1121  253  51  25
MSH6 
 1109  174  549  310  58  3  15
PMS2 
 382  95  98  181  8  0  0
Population-based   2848  89  1792  386  222  53  0
Clinic-based   6015  946  2932  1982  319  62  80
Mutation carriers  20434  3225  10924  5479  799  53  634
Cancers  12827  2951  5742  4340  656  51  508
Colorectal   9711  1692  4469  3561  488  50  244
Endometrial   7638  1201  3532  2651  504  49  206
Ovarian   2808  298  1408  1093  97  3  18
Kidney   830  70  351  463  16  3  2
Pancreas   373  48  150  219  2  0  4
Gastric   115  10  51  53  4  1  4
Prostate   492  82  246  163  16  1  16
Other   226  34  95  112  9  0  0

 

 

NameAffiliationCountry
Abla A Abou-zied University of Alexandria-Egypt Egypt
Adriana Della Valle Uruguayan Collaborative Group, Military Hospital, Montevideo Uruguay
Aída Falcón de Vargas Hospital Vargas, Caracas Venezuala
Aiwen Wu Beijing Cancer Hospital China
Albert de la Chapelle Ohio State University Comprehensive Cancer Center USA
Allan Spigelman St. Vincent’s Hospital, Hunter Family Cancer Service Australia
Allyson Templeton Fred Hutchinson Cancer Research Center USA
Amanda Spurdle Queensland Institute of Medical Research Australia
Amie Blanco University of California San Francisco USA
Anders Bojesen Dept. of Clinical Genetics, Vejle Sygehus Denmark
André Lopes Carvalho Barretos Cancer Hospital Brazil
Angel Alonso Biomedical Research Centre of Health Service of Government of Navarre Spain
Anja Wagner Erasmus Medical Center, Rotterdam Netherlands
Anna Vorster University of Cape Town South Africa
Anne Turner Sydney Children’s Hospital Australia
Anne-Marie Gerdes Dept. of Clinical Genetics, Rigshospitalet, Copenhagen Denmark
Anneke Lucassen Wessex Clinical Genetics Service UK
Annika Lindblom Karolinska Institute Sweden
Aung Ko Win University of Melbourne Australia
Barbara Jung University of Illinois at Chicago USA
Barbara Leggett Genetic Health Queensland Australia
Benedito Mauro Rossi Barretos Cancer Hospital Brazil
Bernie Chodirker Health Sciences Centre, University of Manitoba Canada
Berrin Tunca Uludag University Turkey
Bhramar Mukherjee University of Michigan USA
Bita Nehoray City of Hope, California USA
Brigitte Royer-Pokora Universität Düsseldorf Germany
C. Richard Boland Baylor Health Care System USA
Carin Espenschied Ambry Genetics USA
Carli (C.M.J.) Tops Leiden University Medical Center (LUMC) Netherlands
Carlos Sarroca Uruguayan Collaborative Group, Military Hospital, Montevideo Uruguay
Carlos Vaccaro Hospital Italiano Argentina
Carmen Guillen-Ponce Ramon y Cajal University Hospital, Madrid Spain
Carolina Vergara Uruguayan Collaborative Group, Military Hospital, Montevideo Uruguay
Carrie Snyder Creighton's Hereditary Cancer Center USA
Charlotte Lautrup Aalborg Universitetshospital Denmark
Christina Laukaitis University of Arizona High-risk Cancer Genetics Clinic USA
Christina Rybak City of Hope, California USA
Christina Therkildsen Danish HNPCC Register, Copenhagen University Hospital Denmark
Christoph Engel Institute for Medical Informatics, Statistics and Epidemiology Germany
Daniel Buchanan University of Melbourne Australia
Daniel Chung Massachusetts General Hospital USA
Datuk Dr. Muhammad Radzi Abu Hassan Hospital Sultanah Bahiyah Malaysia
David Amor University of Melbourne Australia
Dawn McIlvried St. Vincent Cancer Care USA
Deb Neklason Huntsman Cancer Institute USA
Dennis Ahnen University of Colorado USA
Doaa Ibrahim Hashad University of Alexandria Egypt
Duck-Woo Kim Korean Hereditary Tumor Registry, Seoul National University Korea
Duncan Thomas University of Southern California (USC) USA
Duveen Sturgeon USC Norris Comprehensive Cancer Center USA
Eamonn R Maher University of Birmingham, Insitute of Biomedical Research (West) UK
Edenir Inez Palmero Barretos Cancer Hospital, Barretos, Sao Paulo Brazil
Elena Stoffel University of Michigan USA
Elizabeth Half Ramban Medical Center Israel
Elke Holinski Feder University Hospital of the Ludwig-Maximilians-University and MGZ Germany
Ellen Kampman Wageningen University, Wageningen Netherlands
Encarna Gomez Garcia Maastricht UMC+ Netherlands
Falil Alwi Universiti Sains Malaysia Malaysia
Fay Kastrinos New York Presbyterian Hospital, Columbia University Medical Center  USA
Finlay Macrae Royal Melbourne Hospital Australia
Fiona Lalloo Central Manchester University Hospitals United Kingdom
Florencia Carussi Uruguayan Collaborative Group, Military Hospital, Montevideo Uruguay
Florencia Neffa Uruguayan Collaborative Group, Military Hospital, Montevideo Uruguay
Florencia Spirandelli Hospital Español de Rosario Argentina
Francisco Lopez-Kostner Clínica Las Condes Chile
Franzel van Duijnhoven Wageningen University, Wageningen Netherlands
Fred H. Menko Family Cancer Clinic, Netherlands Cancer Institute, Amsterdam Netherlands
Frederik J. Hes Leiden University Medical Center (LUMC) Netherlands
Friedrik Wikmann Clinical Laboratory, Aarhus University Hospital Denmark
Gabriel Capella Catalan Institute of Oncology Spain
Gabriela Moeslein HELIOS St. Josefs-Hospital Bochum-Linden Germany
Gareth Evans Central Manchester University Hospitals UK
Geoff Lindeman The Walter and Eliza Hall Institute of Medical Research Australia
George Chong Jewish General Hospital, Montreal Canada
Gillian Mitchell BC Cancer Agency, Vancouver, BC Canada
Gong Chen Sun Yat-sen University Cancer Center China
Graeme Suthers Douglas Hanly Moir Pathology Australia
Grant Lee University of Melbourne Australia
Hans K. Schackert Universitätsklinikum Carl Gustav Carus, Dresden Germany
Hans Morreau Leiden University Medical Center (LUMC) Netherlands
Hans Vasen Leiden University Medical Center (LUMC) Netherlands
Heather Hampel Ohio State University Comprehensive Cancer Center USA
Heinric Williams Geisinger Medical Center, Pennsylvania USA
Henry T. Lynch Creighton's Hereditary Cancer Center USA
Ignacio Blanco Hereditary Cancer Program Spain
Ilana Solomon City of Hope, California USA
Inge Bernstein The HNPCC Register Denmark
Ingrid Winship Melbourne Health Australia
Jack Goldblatt University of Western Australia Australia
Jae-Gahb Park Korean Hereditary Tumor Registry, Seoul National University Korea
James Church Cleveland Clinic, Ohio USA
James Dowty University of Melbourne Australia
James Hill Central Manchester University Hospitals UK
Jan Lowery University of Colorado USA
Jane Green Memorial University of Newfoundland Canada
Jeanette Reece University of Melbourne Australia
Jeffrey Weitzel City of Hope, California USA
Jenny von Salome Karolinska Institute Sweden
Jewel Samadder Huntsman Cancer Institute USA
Joan Levine Stanford Cancer Institute USA
Joanne Young Basil Hetzel Institute, Queen Elizabeth Hospital, Adelaide Australia
Johannes Zschocke
Medical University Innsbruck, Austrian Collaborative MMR Registry
Austria
John Baron Dartmouth Medical School USA
John Burn Institute of Human Genetics, Newcastle University UK
John Hopper University of Melbourne Australia
John Paul Plazzer Royal Melbourne Hospital Australia
John Stubbs Cancer Voices Australia, Inc. Australia
Joji Utsunomiya NPO Biomarker Cancer Prevention Frontier Japan
Jose Guillem Memorial Sloan-Kettering Cancer Center USA
Jose Luis Soto Martinez Molecular Genetics, Hospital Universitario Elche Spain
Judith Karner-Hanusch Medical University of Vienna Austria
Judy Ho The University of Hong Kong, Queen Mary Hospital, Hong Kong China
Judy Kirk Westmead Millennium Institute for Medical Research Australia
Jukka-Pekka Mecklin Department of Surgery, Jyväskylä Central Hospital Finland
Julian Sampson Institute of Medical Genetics, Cardiff University UK
Julie Arnold University of Auckland New Zealand
Junea Caris Oliveira Barretos Cancer Hospital Brazil
Juul Wijnen Leiden University Medical Center (LUMC) Netherlands
Karin Alvarez Clínica Las Condes Chile
Karl Heinimann University Children's Hospital, Basel Switzerland
Kate Green Central Manchester University Hospitals UK
Katharina Wimmer Medical University Innsbruck Austria
Kathleen Blazer City of Hope, California USA
Kathleen Zawaly University of Manitoba Canada
Kathy Tucker Prince of Wales Hospital Australia
Katy Newton Central Manchester University Hospitals UK
Kay Neale St Mark's Hospital, London UK
Kevin Monahan West Middlesex University Hospital UK
Kim Serfas Health Sciences Centre, University of Manitoba Canada
Kim Siegmund University of Southern California USA
Kirsi Pylvanainen Department of Surgery, Jyväskylä Central Hospital Finland
Kiwamu Akagi Saitam Cancer Center Japan
Kohji Tanakaya Dept. of Surgery, Iwakuni Clinical Center Japan
Koh Poh Koon Capstone Colorectal Surgery Centre Singapore
Kory Jasperson Huntsman Cancer Institute USA
Kristina Lagerstedt-Robinson Karolinska Institute Sweden
Kyoung Kim Department of Pathology, Samsung Medical Center Korea
Lara Lipton Cabrini Hospital and Royal Melbourne Hospital Australia
Lars Lindberg Danish HNPCC Register, Copenhagen University Hospital Denmark
Latiefa Jattiem University of Cape Town South Africa
Laura Renkonen-Sinsisalo Helsinki University Central Hospital Finland
Laurent Briollais Samuel Lunenfeld Research Centre Canada
Lea Velsher North York General Hospital Canada
Leigha Senter Ohio State University Comprehensive Cancer Center USA
Lene Juel Rasmussen University of Copenhagen Denmark
Linda Rodgers Massachusetts General Hospital  USA
Lisen Axell University of Colorado Cancer Center USA
Loic LeMarchand Cancer Research Center of Hawaii USA
Lone Sunde Dept. of Clinical Genetics, Aarhus University Hospital Denmark
Lori Arroyo Cleveland Clinic, Florida USA
Lotte Nylansted Krogh Dept. of Clinical Genetics, Odense University Hospital Denmark
Louise Lynagh St. Vincent’s Hospital Australia
Luigi Ricciardiello University of Bologna Italy
Luis Carvajal-Carmona Univ of Oxford, and UC Davis, California, and Univ of Tolima UK, USA, Colombia
Lyn Scholfield University of Western Australia Australia
Maartje Nielsen Leiden University Medical Center (LUMC) Netherlands
Magnus v. K. Doeberitz Universitätsklinikum Heidelberg, Heidelberg Germany
Magreet Ausems Universital Medical Centre Utrecht (UMCU) Netherlands
Maija Kohonen-Corish Garvan Institute Australia
Mala Pande M.D. Anderson USA
Malcolm Dunlop University of Edinburgh UK
Marc Greenblatt University of Vermont College of Medicine USA
Maria Soller Dept. of Clinical Genetics, Lund University Hospital Sweden
Mariana Niell-Swiller City of Hope, California USA
Marie Luise Bisgaard Dept. of Clinical Genetics, Vejle Sygehus, Vejle Denmark
Marie-Odile North Oncogenetique Biochimie Genetique Pavillon, Dausset Hospital France
Marina Antelo Hospital de Gastroenterologia Dr. Carlos Bonorino Udaondo Argentina
Marion Harris Southern Health Familial Cancer Centre Australia
Marjolijn Ligtenberg Radboud University Medical Center, Nijmegan Netherlands
Mark Jenkins University of Melbourne Australia
Markus Loeffler Institute for Medical Informatics, Statistics and Epidemiology Germany
Marta Sapone Uruguayan Collaborative Group, Military Hospital, Montevideo Uruguay
Martin Delatycki Austin Health Australia
Masami Arai Dept. of Clinical Genetic Oncology, Cancer Institute Hospital Japan
Matthew Kalady Cleveland Clinic, Ohio USA
Maurizio Genuardi University of Florence Italy
Mef Nilbert Regional Cancer Centre South Sweden
Megan Hitchins Cedars-Sinai Medical Center, California USA
Melissa Southey University of Melbourne Australia
Melyssa Aronson Familial GI Cancer Registry, Mount Sinai Hospital Canada
Mercy Laurino Seattle Cancer Care Alliance (SCCA) USA
Mev Dominguez Valentin University of Oslo Norway
Michael Farrell Mater Private Hospital, Dublin Ireland
Michael Gattas Brisbane Genetics Australia
Michael Hall Fox Chase Cancer Center USA
Mike Woods Memorial University of Newfoundland Canada
Nagahide Matsubara Department of Surgery, Hyogo College of Medicine Japan
Naohiro Tomita Department of Surgery, Hyogo College of Medicine Japan
Nancy Uhrhammer Centre Jean Perrin, D'Auvergne France
Nancy You M.D. Anderson USA
Nicola Poplawski Women's and Children's Hospital, Adelaide Australia
Nicoline Hoogerbrugge Radboud University Medical Center, Nijmegan Netherlands
Nida Jamal Washington University, St. Louis USA
Niels de Wind Leiden University Medical Center (LUMC) Netherlands
Nora Artagaveytia Uruguayan Collaborative Group, Military Hospital, Montevideo Uruguay
Noralane Lindor Mayo clinic USA
Pål Møller Norwegian Radium Hospital, Oslo University Hospital Norway
Patricia Esperon Uruguayan Collaborative Group, Military Hospital, Montevideo Uruguay
Patrick Lynch M.D. Anderson USA
Patrick Morrison Belfast HSC Trust UK
Paul Wise Washington University, St. Louis USA
Peirong Ding Sun Yat-sen University Cancer Center China
Pilar Carvallo Pontificia Universidad Católica de Chile Chile
Pilar Garre Hospital Clinico San Carlos, Madrid Spain
Polly Newcomb Fred Hutchinson Cancer Research Center USA
Rachel Susman Genetic Health Queensland Australia
Raj Ramesar University of Cape Town South Africa
Rakefet (Ricki) Shtoyerman The Kaplan Medical Center Israel
Randy Burt Huntsman Cancer Institute USA
Ravi Sharaf Long Island Jewish Medical Center, University School of Medicine USA
Reinhard Buettner Institut für Pathologie Köln Germany
Revital Kariv Tel Aviv Sourasky Medical Center registry Israel
Richard Fishel Ohio State University USA
Robert Haile Cedars-Sinai Medical Center, California USA
Robert Hofstra Universital Medical Centre Groningen Netherlands
Robin Bennett The Genetic Medicine Clinic at the University of Washington USA
Robyn Ward Prince of Wales Hospital / University of New South Wales Australia
Rodney Scott University of Newcastle Australia
Rodrigo Guindalini University of Chicago USA
Rolf Sijmons Universital Medical Centre Groningen Netherlands
Rui Manuel Reis Barretos Cancer Hospital, Barretos, S. Paulo Brazil
Rupa Sood Memorial Sloan-Kettering Cancer Center USA
Samuel Gebre-Medhin Department of Clinical Genetics, University Hospital, Lund Sweden
Sanne ten Broeke Leiden University Medical Center (LUMC) Netherlands
Sapna Syngal Dana Farber Cancer Institute USA
Sara Miccoli University of Bologna Italy
Sean Tavtigian Huntsman Cancer Institute USA
Seung-Yong Jeong Korean Hereditary Tumor Registry, Seoul National University Korea
Sharon Cohen Long Island Jewish Medical Center, University School of Medicine USA
Sheila Solomon University of Pittsburgh Medical Center USA
Shuyuan Cheng Sun Yat-sen University Cancer Center China
Sonia Kupfer University of Chicago USA
SoYoung Kang Department of Pathology, Samsung Medical Center Korea
Stacey Shiovitz Seattle Cancer Care Alliance USA
Stefan Aretz University of Bonn Germany
Steve Gallinger University of Toronto Canada
Steve Gruber University of Southern California USA
Steve Thibodeau Mayo Clinic USA
Suet Yi Leung University of Hong Kong China
Susan Fay Cleveland Clinic, Ohio USA
Susan Parry University of Auckland New Zealand
Susanne Timshel Dept. of Clinical Genetics, The Kennedy Center, Glostrup Denmark
Sylviane Olschwang Institut Paoli-Calmettes France
Tadashi Nomizu Hoshi General Hospital Japan
Takeshi Nakajima Endoscopy Division, National Cancer Center Hospital Japan
Tatsuro Yamaguchi Center Koagome Hospital Japan
Theo van Os Amsterdam Medical Centre (AMC)/VU University Medical Center Netherlands
Thomas Slavin City of Hope, California USA
Thomas v. O. Hansen Center for Genomic Medicine, Copenhagen University Hospital Denmark
Thomas Weber State University of New York & Veterans Health Administration USA
Tina Pesaran Ambry Genetics USA
Tom van Wezel Leiden University Medical Center (LUMC) Netherlands
Tomoyuki Momma Hoshi General Hospital Japan
Toni Seppala Helsinki University Central Hospital Finland
Trinidad Caldes Hospital Clinico San Carlos, Madrid Spain
Uffe Birk Jensen Dept. of Clinical Genetics, Aarhus University Hospital Denmark
Uri Ladabaum Stanford Cancer Institute USA
William Grady Seattle Cancer Care Alliance USA
Wolff H. Schmiegel Medizinische Universitätsklinik, Bochum Germany
Yoshinori Akama Hoshi General Hospital Japan
Yun-Hee Choi Schulich School of Medicine & Dentistry, Western University Canada
Zohar Levi Dept Rabin Medical Center Israel

 

 

 

Worldwide Study of Cancer Risks for Lynch Syndrome

Principal Investigator: Mark A. Jenkins, The University of Melbourne

Accurate risk estimates are needed to inform genetic counselling guidelines and the clinical management of high-risk families. The only way to address these problems is to conduct comprehensive penetrance analyses on large, ethnically heterogeneous samples of persons/families segregating mutations in MMR genes. To address these critical research needs, we will: (i) establish a combined data set of pedigree data from around the world for approximately 8,800 Lynch syndrome families; (ii) estimate the age-specific cumulative risk (penetrance) of cancers at each anatomical site by sex, mismatch repair gene, type of mutation, and nationality/geographic region; and (iii) develop a personal risk tool for clinical use that provides 10-year risks of cancer based on the age, sex, mismatch repair gene, type of mutation, and nationality/geographic region.

Click this link to view the data dictionary.

  • Mark Jenkins (co-founder)
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  • Aung Ko Win
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  • Jeanette Reece (coordinator)
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Mismatch Repair Variant Classification

Principal Investigators: Marcus Greenblatt, University of Vermont; Sean Tavtigian, University of Utah

In clinical cancer genetics, molecular diagnostic testing is now commonly performed looking for pathogenic mutations in cancer susceptibility genes. A critical challenge in the field is interpreting whether a genetic variant causes disease or not. About 20-30% of the variants identified in MMR and other cancer susceptibility genes are missense or non-coding changes that may or may not be pathogenic, but whose effects on function and disease cannot be interpreted easily. They are designated “Variants of Unknown Significance”. Classifying variants as pathogenic and neutral significantly improves the management of LS and other hereditary cancer syndromes by identifying which individuals carry a harmful genetic variant and thus benefit from screening and therapeutic measures.  To address these needs we will: (i) generate a list of MMR missense variants and how they are classified using available data and criteria; (ii) validate and quantify the classifying ability of in vitro, in silico, and clinic-pathologic data; and (iii) create qualitative and quantitative models to classify variants.

  • Marcus Greenblatt
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  • Sean Tavtigian
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Worldwide Study of Genetic Testing and Cancer Screening in Lynch Syndrome

Principal Investigator: Robert Haile, Cedars-Sinai Medical Center, California, USA

Development of successful programs to increase the use of colonoscopy screening within Lynch syndrome family members depends on the availability and uptake of genetic testing of relatives in families with documented Lynch syndrome mutations.  Therefore an understanding of the variables underlying the choice of individual family members to be tested is important for reducing the burden of colorectal cancer screening in Lynch syndrome families. Colonoscopy screening has been demonstrated to significantly decrease both colorectal cancer incidence and mortality in Lynch syndrome. Additional studies in more racial/ethnic groups and in more countries and with longer follow-up are needed to better understand current compliance with screening guidelines and the reasons for lack of screening among those who harbor a deleterious mutation in a mismatch repair gene. Such information is as prerequisite to design methods to increase compliance with screening guidelines in this very high-risk population.  To address these needs we will: (i) clarify the country-specific guidelines for genetic counselling and testing for Lynch syndrome families and then collect data on the uptake of genetic counselling/testing by members of Lynch syndrome families; (ii) clarify country-specific guidelines for cancer screening in Lynch syndrome and then collect data on compliance with screening guidelines by members of Lynch syndrome families; and (iii) conduct focus groups to better understand “local”, country-specific barriers to compliance.

  • Robert Haile (co-founder)
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Collaborative Study on the Role of Lifestyle Factors/Diet/Body Fatness in the Development of Tumours in Lynch Syndrome

Principal Investigator: Franzel van Duijnhoven, Wageningen University

Lifestyle factors have a pronounced effect in those at a very high lifetime risk of cancer due to an inherited mutation: being overweight and smoking strongly increases the risk of colorectal tumours in persons with Lynch syndrome. Other lifestyle factors such as diet as well as other outcomes such as endometrial cancer in Lynch syndrome have not or only scarcely been studied. To further elucidate the role of lifestyle factors in the development of tumours in persons with Lynch syndrome, large populations with a variety in lifestyle habits are needed. Therefore, we propose to cooperate internationally and set-up a worldwide collaborative study on the role of lifestyle factors/diet/body fatness in the development of tumours in Lynch syndrome. To do this, we will: (i) perform a pilot study on smoking and overweight in relation to cancer risk in those cohorts that already have this information available; and (ii) write a large grant application (which includes the results from the pilot study) to collect and analyse data on lifestyle/diet/body fatness for all cohorts in our worldwide collaborative study. Our ultimate goal is to develop evidence-based lifestyle recommendations to decrease the risk of cancer in persons with Lynch syndrome.

  • Franzel van Duijnhoven
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  • Ellen Kampman
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MLH1 Epimutations in Predisposing to the Development of Lynch-type Tumors

Principal Investigator: Megan Hitchins, Cedars-Sinai Medical Center, California, USA

MLH1 epimutations manifests high levels of MLH1 methylation throughout normal tissues, and though comparatively rare, may account for a significant fraction of Lynch-type cases whose tumors demonstrate MLH1 absence but who have no germline sequence mutation of MLH1. Given its rarity, meaningful comprehensive studies will benefit from collaboration on an international scale. To address these needs we will: (i) establish the frequency of MLH1 epimutations in cases with a clinical suspicion of Lynch syndrome by testing the colorectal cancer cases clinically suspected of Lynch syndrome, but for whom no pathogenic mutation can be identified; (ii) measuring the clinical phenotype of epimutation carriers to gain a more detailed clinical profile; (iii) measuring the molecular profiling of tumors in epimutation-positive cases to determine the "second hit" plus more detailed TGCA-type analysis to elucidate the tumor molecular phenotype; and (iv) determining the inheritance patterns associated with MLH1 epimutations and the mechanisms underlying them by studying family members of epimutation carriers.

  • Megan Hitchins
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Cancer Risk in Family Members of CMMR-D Patients

Principal Investigator: Maartje Nielsen, Leiden University Medical Center

Risk of cancer is high for people who have inherited a mutation in a mismatch repair gene from both parents and therefore have constitutional mismatch repair-deficiency (CMMRD). However very little is known about the risks of cancer for their relatives on both sides of their family who carry a mutation (most often in the PMS2-gene). Understanding these risks is important for the clinical care of family members of CMMRD patients. Studying such relatives provides an unbiased estimate of cancer risk for heterozygous MMR mutation carriers in general. This is because in principal CMMRD families are ascertained because of the distinct phenotype of the index case, not because of family history of cancer. Due to the increased use of detection methods for Lynch syndrome, such as standardized IHC/MSI analysis in all CRC cases, and next generation sequencing, there will be an increase in the detection of apparently sporadic Lynch syndrome cases. For these patients knowledge on unbiased cancer risk is important to provide justified screening protocols. To address this gap, we will: (i) determine retrospectively the cancer risk in family members (up to third degree) of patients with CMMR-D; and (ii) conduct a follow-up study of family members with an identified heterozygous MMR mutation to prospectively estimate risk of cancer.

  • Maartje Nielsen
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