Nutritional and Metabolic Diseases

Gland and Hormone Related Diseases

All Conditions

Symptoms and General Pathology

Neoplasms

Digestive System Diseases

Rare Diseases

Diabetes Mellitus

Recurrence

Pancreatic Neoplasms

Pancreatitis

Pancreatitis, Chronic

Pancreatic Diseases

Gastrointestinal Diseases

Chronic Disease

Disease Attributes

Pancreatic Cancer

Chronic Graft Versus Host Disease

Acute Graft Versus Host Disease

Gastrointestinal Agents

All Drugs and Chemicals

Pancrelipase

Pancreatin

At least 2 episodes of acute pancreatitis with complete resolution of pain and a \>1 month pain-free interval between episodes.

Children with at least:

1) One irreversible structural change\* in the pancreas with or without abdominal pain +/- exocrine pancreatic insufficiency +/- diabetes.

\*irreversible structural changes:

* Ductal calculi, dilated side branches, parenchymal calcifications found in any imaging (abdominal ultrasound (abd US), magnetic resonance imaging/magnetic resonance cholangiopancreatography (MRI/MRCP), computerized tomography (CT), endoscopic retrograde cholangiopancreatography (ERCP), endoscopic US (EUS).
* Ductal obstruction or stricture/dilatation/irregularities that are persistent (for \>2 months) on any imaging.
* Parenchymal atrophy, irregular contour, accentuated lobular architecture, cavities alone are not diagnostic findings for CP.
* Surgical or pancreatic biopsy specimen demonstrating histopathologic features compatible with CP (acinar atrophy, fibrosis, protein plugs, infiltration with lymphocytes, plasma cells, macrophages).

Six ml of blood will be collected from patients in an EDTA tube. 2 ml saliva samples in Oragene DNA collection kits

Blood sample

Questionnaires will be completed at the baseline and annual follow-up visits to collect data that will define the demographics of the pediatric ARP and CP cohort, describe risk factors, presence of family history of acute and chronic pancreatitis, diabetes and pancreatic cancer and assess disease burden and sequelae.

Patient questionnaires

2 ml saliva samples in Oragene DNA collection kits collected if no blood sample being collected.

Saliva sample

Urine sample

Ying Yuan, Ph.D

The investigators will enroll a total of 628 patients under 18 years of age with ARP or CP. Included in the total are the 357patients in the INSPPIRE 1 database who are planned to be reenrolled under this protocol over the next 4 years. Patient questionnaires and physician surveys will be applied at the time of enrollment and annually thereafter as long as possible. At the first study visit after turning 18 years of age, the patient will sign the informed consent to continue in the study. Specifically, the investigators will define the demographics of the pediatric ARP and CP cohort, describe risk factors, presence of family history of acute and chronic pancreatitis, diabetes and pancreatic cancer and assess disease burden and sequelae.

Disease Burden Pain. The pattern of the pain (constant versus episodic), its frequency, duration, visits to the emergency room or hospitalizations for pain, impact of pain on quality of life will be recorded in questionnaires. The intensity of the pain will be measured at enrollment, during an attack and annually using FACES Pain Scale-Revised, a self-report questionnaire validated for children \>4 y/o. The names, dosing and frequency of medications taken for pain will also be queried.

Health-Related Quality of Life (HRQOL). An age-specific instrument validated for United States children will be used to measure HRQOL at enrollment and annually thereafter. Parents of children 5-18 years old will complete Child Health Questionnaire Parent Form 50 questions (CHQ PF-50). Children \>10 years old will answer Child Health Questionnaire Child Form 87 questions (CHQ-87). Adults \>18 years old will not complete a health-related questionnaire. These questionnaires capture physical functioning, social, emotional, physical and behavioral limitations, bodily pain, general behavior, mental health, self-esteem, general health perceptions, change in health and parental emotional impact.

Depression and anxiety. Depression and anxiety are strong predictors of chronic pain and pain-related disability in children, but it is not known whether this applies to children with ARP or CP. The investigators will assess for depression and anxiety in the INSPPIRE cohort at the time of enrollment and annually thereafter. The investigators will utilize the Child Behavioral Checklist (CBCL), one of the most widely-used standardized measures in child psychology for evaluating maladaptive behavioral and emotional problems in preschool subjects aged 1½ to 5 years and in school-age subjects between the ages of 6 and 18. For preschool-age children, the CBCL/1½-5 (completed by parents or surrogates) will be used. For school-age children 6-18 y/o, the investigators will utilize CBCL/6-18 y/o (completed by parents or surrogates). Children who are 11-18 y/o will answer a self-report questionnaire (Youth-Self Report Form or YSR/11-18). CBCL assesses internalizing (i.e., anxious, depressive, and over controlled) and externalizing (i.e., aggressive, hyperactive, noncompliant, and undercontrolled) behaviors. Adults \>18 years old will not complete a behavioral checklist.

Patients/parents will spend approximately 2 hours answering questionnaires; their time will be compensated at $50 per visit. Patients will be enrolled during clinic visit as outpatient or as an inpatient. Alternatively, questionnaires can be applied over the phone or completed at home and returned via mail if the patient is unable to travel. Self-addressed stamped envelopes will be given to the patient/parent as needed for returning the questionnaires.

Disease Sequelae

The presence of exocrine pancreatic insufficiency and glucose intolerance/diabetes will be monitored at the time of enrollment and annually thereafter. Monitoring will include specifically:

1. Exocrine pancreatic insufficiency: defined as the presence of abnormal fecal elastase (\< 100 ug/ g stool on 2 separate samples ≥ 1 month apart) or abnormal serum trypsin or serum trypsinogen.
2. Diabetes or prediabetes: Monitoring for diabetes in our cohort will include once yearly assessments with fasting glucose (diabetes range if ≥ 126 mg/dL), HbA1c (abnormal if \>6; diabetic if \>6.5%) and oral glucose tolerance test (OGTT). For OGTT, 1.75 grams/kg of standard glucose beverage (glucola, maximum 75 grams) will be consumed within 10 minutes at time 0. Glucose will be drawn prior to the beverage and at time 120 minutes. From this test, glycemic status will be defined as: (1) normal glucose tolerance (NGT, fasting glucose \<100 mg/dL, 2 hour \<140 mg/dL); (2) pre-diabetic based on impaired fasting glucose (IFG, fasting glucose 100-125 mg/dL) and/or impaired glucose tolerance (IGT, 2 hour glucose 140-199 mg/dL); or (3) diabetic (DM, fasting glucose \>126 mg/dL or 2 hour glucose \>200 mg/dL).
3. Nutritional status including micronutrient deficiency: To determine the nutritional sequelae of ARP or CP in children, the investigators will assess for malnutrition/obesity (weight, height, BMI, z scores; body fat mass and lean mass as measured by DXA scan), fat soluble vitamin deficiencies (serum vitamin levels for A, D, and E and bone density (DXA scan) in children with ARP or CP at the time of enrollment and annually thereafter.

The investigators will identify subjects within our cohort that presented with acute recurrent pancreatitis episodes, normal exocrine and endocrine pancreas function and normal pancreas imaging without any signs of chronicity (ARP cohort). The investigators will identify the development of CP on an annual basis as long as possible, as well as development of sequelae and disease burden as listed above.

Prospective Registry

The investigators will develop a database of children with ARP and CP. This will provide a cohort of well-phenotyped subjects for future studies targeting pathogenesis and novel therapies. The investigators will establish a process by which investigators outside of the consortium may have access to the data and biospecimens.

At enrollment, via the informed consent, subjects will choose whether or not to allow use of their biological samples for this study, future research, genetic analysis, genetic analysis for future research, and any type of future research. They will also choose whether or not we may keep their name and personal information in a registry to allow us to contact them for other future research.

BIOSPECIMEN COLLECTION

Sample collection for deoxyribonucleic acid (DNA): The subject will be able to give either blood or saliva. Six ml of blood will be collected from subjects in an ethylenediaminetetraacetic acid tube or 2 ml saliva samples in Oragene DNA collection kits then labeled with the barcoded specimen labels provided by the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC) Coordinating Center. The specimen labels provided by CPDPC include a specimen identification (ID) number and barcode. Subject identifiers (for example names or initials) are not included on the labels. Before shipping the specimens to the central repository the specimen ID number from the label will be connected to the patient information in the CPDPC's secure IIMS Specimen Manager system. After the specimen ID number is linked to the subject in the CPDPC system the samples will be submitted to the central repository for the study via overnight courier. The central repository for DNA will be at the University of Iowa. The central repository at Iowa will not have access to the link that connects to the patient's personal identifiers in the Integrated Information Management System (IIMS). The central repository will log receipt of the specimens into the CPDPC IIMS Specimen Manager system using the specimen ID from the labeled vials. The central repository will process the specimens into aliquots for the extraction of genomic DNA following the CPDPC specimen processing described in the appendices. The aliquots will be labeled with CPDPC supplied labels and stored in a freezer at -80 degree Centigrade. The CPDPC aliquots labels contain barcodes and specimen ID numbers that do not link the aliquots to each other. The only link to the subject information resides in the secured database at the CPDPC coordinating and data management center. The central repository laboratory staff and the study researchers do not have access to this link. At the end of the study the specimens stored in the central repository at Iowa will be transferred to a central repository at National Institute of Diabetes and Digestive and Kidney Diseases.

Urine collection for bio-markers: To be completed only at sites identified by the lead site to collect urine samples. Not all sites will be collecting urine. See Appendix 14.27 for collection and processing instructions. The subject will be instructed to collect a minimum of 50 mL clean-catch urine sample. A dipstick urine analysis will be performed immediately after urine collection. Urine samples will then be kept on wet ice or refrigerated until processed. Samples will be processed within 4 hours of collection. Samples will be labeled with the barcoded specimen labels provided by the CPDPC Coordinating Center. The specimen labels provided by CPDPC include a specimen ID number and barcode. Subject identifiers (for example names or initials) are not included on the labels. Before shipping the specimens to the central repository the specimen ID number from the label will be connected to the subject information in the CPDPC's secure IIMS Specimen Manager system. After processing, samples will be frozen at -80ºC. The urine processing log sheet will be completed. Samples will be stored and batch shipped to the Central repository at University of Iowa annually. The central repository will log receipt of the specimens into the CPDPC IIMs Specimen Manager system using the specimen ID from the labeled vials. The central repository at University of Iowa will not have access to the link that connects the subject's personal identifiers in the IIMS system. The central repository will log receipt of the specimens into the CPDPC IIMS Specimen Manager system using the specimen ID from the labeled vials. The CPDPC aliquots labels contain barcodes and specimen ID numbers that do not link the aliquots to each other. The only link to the subject information resides in the secured database at the CPDPC coordinating and data management center. The central repository laboratory staff and the study researchers do not have access to this link. At the end of the study the specimens stored in the central repository at Iowa will be transferred to a central repository at NIDDK.

6 ml blood sample or 2 ml saliva sample collected 1 time. Urine 50 ml collected one time

Pediatric Longitudinal Cohort Study of Chronic Pancreatitis

Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC) CPDPC16-03 Pediatric Longitudinal Cohort Study of Chronic Pancreatitis

Date of diagnosis of first acute pancreatitis to date of diagnosis of chronic pancreatitis presented as minimum, maximum, median number of days and no progression to chronic pancreatitis.

Presence of abdominal pain in the past year presented as number with "Yes", "No", "I don't know" and missing responses.

Presence of constant abdominal pain described as number of subjects with "Yes", "No", "I don't know" and missing responses.

Number of subjects who are usually pain free with episodes of abdominal pain described as number with "Yes", "No", "I don't know" and missing responses..

Number of emergency room visits subjects experienced in the past 12 months presented as minimum, maximum, and median number of emergency room visits and number of missing responses.

Number of emergency room visits the subject experienced in their whole life presented as minimum, maximum, and median number of visits and number of missing responses..

Number of hospitalizations subject experienced in the past 12 months presented as minimum, maximum, and median number and number of missing responses..

Number of hospitalizations subject had in their whole life presented as minimum, maximum, and median number and number of missing responses..

Number of school days subject missed in the last month presented as minimum, maximum, and median number and number of missing responses..

Number of subjects with abnormal fecal elastase (\< 100 micrograms/ gram of stool on 2 separate samples ≥ 1 month apart) presented as number of subjects with abnormal and normal lab values and number of subjects who did not have test done.

Number of subjects with fasting glucose ≥126 milligrams per deciliter presented as number of subjects with abnormal and normal lab value and number of subjects who did not have test done.

Number of subjects with HbA1c (abnormal if \>6; diabetic if \>6.5%) results that were normal, abnormal, and diabetic and number who did not have test done.

Number of subjects with abnormal OGTT test results. OGTT performed with 1.75 grams/kilogram of standard glucose beverage (glucola, maximum 75 grams) consumed within 10 minutes at time 0. Glucose drawn prior to the beverage and at time 120 minutes. Glycemic status will be defined as: (1) normal glucose tolerance (NGT, fasting glucose \<100 mg/dL, 2 hour \<140 mg/dL); (2) pre-diabetic based on impaired fasting glucose (IFG, fasting glucose 100-125 mg/dL) and/or impaired glucose tolerance (IGT, 2 hour glucose 140-199 mg/dL); or (3) diabetic (DM, fasting glucose \>126 mg/dL or 2 hour glucose \>200 mg/dL). Findings presented as number of subjects with normal, pre-diabetic, impaired, and diabetic results and number that did not have test done.

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

National Cancer Institute (NCI)

Aliye Uc

Professor

Behaviors and Mental Disorders

Esophageal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Head and Neck Neoplasms

Esophageal Diseases

Esophageal Cancer

Quality of Life

100 disease free survivors who underwent multimodality treatment for oesophageal adenocarcinoma and are \>1 year post oesophagectomy

Participants will attend an outpatient clinic, fasted for at least 4 hours for collection of breath.

Breath test

Participants will attend an outpatient clinic, fasted for at least 4 hours for collection of saliva.

Participants will attend an outpatient clinic, fasted for at least 4 hours for collection of blood.

Participants will attend an outpatient clinic, fasted for at least 4 hours for collection of urine.

Participants will attend an outpatient clinic, fasted for at least 4 hours for collection of stool.

Stool sample

Participants will attend an outpatient clinic and complete validated healthy-related quality-of-life questionnaires.

Health-related Quality of life questionnaires

Dr Munir Tarazi, MB BCh BAO MRCS MCh

Munir Tarazi, MB BCh BAO MRCS MCh

The goal of this observational study is to learn about long term symptoms in oesophageal cancer survivors. The main question it aims to answer is are:

* Study the changes in gut bacteria by examining saliva, stool and blood.
* Investigate the products of bacteria in breath to develop a non-invasive breath test to detect the changes in gut bacteria.
* Develop new strategies to treat this change and trial new treatments to improve quality- of-life in oesophageal cancer survivors.

Participants will attend an outpatient clinic, fasted for at least 4 hours for collection of breath, saliva, blood, urine, stool and complete validated healthy-related quality-of-life questionnaires.

Researchers will compare symptomatic and asymptomatic participants to detect the changes stated above.

Profiling Microbiome Associated Metabolic Pathways in Oesophageal Cancer Survivors

Metagenomic sequencing of saliva samples.

Bioinformatic multi-omic pathway analysis.

Gas Chromatography-Mass Spectrometry (GC-MS) will be used to identify the levels (measured in parts per billion, ppb) of certain microbiome-derived VOCs in breath.

Identify therapeutic targets and interventions to manipulate dysbiotic microbiota

Imperial College Healthcare NHS Trust

West Hertfordshire Teaching Hospitals NHS Trust

Barking, Havering and Redbridge University Hospitals NHS Trust

Imperial College London

Skin and Connective Tissue Diseases

Breast Neoplasms

Breast Diseases

Skin Diseases

All women will be interviewed by telephone using the a similar questionnaire as used in the parent study. DNA samples will be obtained either via blood samples drawn during a home or clinic visits, or an Oragene Saliva DNA Self-Collection Kit sent to the participant's home.

Take part in an approximately 45 minute telephone interview, with questions about detailed treatment (chemotherapy, hormonal therapy, radiation therapy (RT)) for all study participants. Their medical records will be reviewed to get further details about treatment of their breast cancer. They donate either a 35 ml blood sample (about 3 tablespoons) or a saliva sample. Blood Sample: if patient consents to give a blood sample, following the interview, they will be contacted by our staff phlebotomist (a person trained to draw blood). A scheduled appointment to draw a blood sample from you at your home. At the time of the blood draw, the phlebotomist will collect approximately 2 and 1/3 tablespoons of blood. Saliva Sample: if they choose not to give a blood sample, but consent to give a saliva sample instead, a saliva kit will be sent to there home. Once they provide the sample in the kit, they will be asked to mail back the sample in the pre-labeled kit that was sent to them.

questionaire, blood or saliva sample

Jonine Bernstein, PhD

This study is being done to find out what factors may be related to the risk of getting a second breast cancer among women who already have breast cancer in one breast. It will look at how genes, treatment for breast cancer; including radiation therapy, and the effects of different lifestyle activities, may affect the risk of breast cancer. It will use different processes to find genes that might increase the risk of breast cancer. The results of this study may help to develop better ways to detect, treat and prevent breast cancer. This study will compare women who have breast cancer in both breasts to women who have breast cancer in only one breast.

This study expands upon an existing case-control study we call the Women's Environment Cancer and Radiation Epidemiology (WECARE) Study. For simplicity, in this protocol, we will refer to that study as the "parent" study. The goal of both studies is to examine the interaction of radiation exposure and genetic susceptibility factors in the etiology of breast cancer. A subset of study participants who consented to 'future contact' in the GWA Study (and those in the 'parent' study from selected sites) will be included in an analysis of radiation-related heart disease and related conditions.

Study of Radiation Exposure and Bilateral Breast Cancer

Genome-Wide Association Study of Radiation Exposure and Bilateral Breast Cancer

Translational Genomics Research Institute

University of Southern California

University of Virginia

Lund University

Ontario Cancer Registry (OCR) and Mount Sinai Hospital- Toronto (MSHT)

Northern California Cancer Center

Fred Hutchinson Cancer Center

University of Iowa

Danish Cancer Society

Beckman Research Institute

City of Hope National Medical Center

M.D. Anderson Cancer Center

Vanderbilt University School of Medicine

NYU Langone Health

University of Chicago

University of California, Irvine

Stanford University

Memorial Sloan Kettering Cancer Center

Respiratory Tract (Lung and Bronchial) Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Lung Neoplasms

Prostatic Neoplasms

Current smokers with cancer who are planning to get radiation therapy at MUSC.

Subjects will be asked to complete a survey asking questions about his/her current health, well-being and quality of life.

Survey

Subjects will have saliva collected by a member of the study team using a cotton swab.

Subjects will be asked to complete an assessment asking questions about his/her current smoking status

Smoking Status questions

Graham Warren, MD, PhD

The purpose of this study is to improve cancer care and the delivery of cancer care. Researchers are interested in studying patient reported information and examining how different factors may impact cancer care.

Improving Evidence-Based Care for Cancer Patients

Biochemical confirmation will be determined by saliva samples

Self-reported smoking cessation will be documented via smoking assessment questionnaire

reported cigarettes per day multiplied by the number of days smoked during radiation therapy (RT), summed over a period of time and normalized to yield an average weekly smoke exposure during RT.

Completing one in-person visit where an individualized smoking cessation treatment plan is developed and implemented.

Two binary measure of compliance:

1. - completing at least three in person visits within 6 weeks of starting an individualized cessation treatment plan
2. - completing at least one in-person visit and at least two phone-based communications

National Institutes of Health (NIH)

Medical University of South Carolina

Uterine Cervical Neoplasms

Endometriosis

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Leiomyoma

Myofibroma

Genital Diseases, Female

Uterine Neoplasms

Cysts

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Diseases

Ovarian Cancer

Ovarian Epithelial Cancer

Clinically symptomatic females with one or more of the following gynecological pathology:

* Endometriosis,
* Adenomyosis,
* Ovarian cysts,
* Fibroids,
* Ovarian cancer,
* Cervical cancer
* Uterine cancer.

Asymptomatic females with:

* Cervical dysplasia or cancer
* A normal pap-smear (control)

Sofiane Bendifallah, MD

GynRAN is an international, multicentre, transversal, diagnostic and non-interventional study carried out in gynecology-obstetrics/gynecological oncology departments that aims to identify a diagnostic signature for gynecological pathologies by analyzing of coding and non-coding RNA contained in patients saliva.

The study population consists of patients with clinically symptomatic females with one or more of the gynecological pathologies (endometriosis, adenomyosis, ovarian cysts, fibroids, ovarian/cervical/uterine cancer) and asymptomatic females.

The patients concerned by the study will be managed without modification of the care pathway, nor modification of the therapeutic indications, nor modification of the diagnostic or follow-up examinations necessary according to the context, which are carried out according to the local recommendations.

Evaluation of Salivary RNA in Subjects Scheduled for Surgery for a Gynecologic Pathology

Identify a diagnostic signature for each pathology (Endometriosis / Adenomyosis / Ovarian cysts / Fibroids / Cervical Displasia / Ovarian cancer / Cervical cancer /Uterine cancer) by analyzing of coding and non-coding RNA contained in the saliva.

Monitoring Force Group

ZIWIG

Affected individuals with a family history of 5 or more discordant cancers in unilateral descent with a 3-generation pedigree will receive SOC CLIA/CAP multicancer panel (DNA collected via blood draw or punch biopsy) to examine monogenic variant diagnostic yield. Eligible participants (families with no mutations and at least 2 affected and 1 non-affected family members) may move forward with WES.

Any identified monogenic variants of interest will be sent to an industry partner with CLIA/CAP certification for validation. A 6-month follow-up visit will take place during which variants will be discussed and participants who underwent gHFI variant counting (those who were not considered a gene candidate) will have results explained. Appropriate genetic counselling, recurrence risk, and additional clinical referrals will be made as necessary

Affected individuals (cancer) with a family history suggestive of a known hereditary syndrome or meeting NCCN criteria for germline testing will receive SOC CLIA/CAP multicancer panel in order to examine monogenic variant diagnostic yield (retrospective data)

This arm would also include prospective participants from the "5 or more discordant cancers" group who DID have a variant identified and therefore did not move on to WES.

Sequencing will be performed on an Illumina sequencing system

WES via Illumina NextSeq 550 sequencing system

Blood draw will be via any University Hospitals Laboratory site and sent at room temperature via courier to the Center for Human Genetics (CHG) Laboratory

Blood Draw

Skin samples obtained via 3mm punch biopsy will be suspended in cell culture media prepared per CHG routine and sent via courier to the Center for Human Genetics Laboratory

Skin biopsy

Participant will provide a saliva sample which be shipped to University Hospitals Laborator site at room temperature

Saliva Sample

Anna Mitchell, MD PhD

Anna Mitchell, MD, PhD

The purpose of this study is to identify novel gene mutations which have contributed to significant personal and family history of cancer. Adults with and without cancer will be accrued to the study. Participants qualify to take part in this research study because someone in their family has been diagnosed with or because they themselves have a cancer diagnosis.

Participants' DNA and other clinical information will be obtained from a blood sample in order to study the genetic basis of cancer and related complications. All portions in the DNA that code for proteins (i.e., the exome) will be studied. Participant DNA sample and information about family structure and family medical history and ethnic origin may also be collected to better understand this information. Clinical information will be stored and biological samples, including DNA, will be kept for up to three (3) years after collection for future. Ultimately, once identified, the role of the specific genetics changes in the development of inherited cancer(s) will be characterized.

Data for this study will be obtained via both retrospectively and prospectively. Affected individuals (who have cancer) with a family history suggestive of a known hereditary syndrome or meeting National Comprehensive Cancer Network (NCCN) criteria will be accrued from routine clinical care to form a "real world" baseline of diagnostic yield using a multicancer panel. These participants will not be additionally consented for WES as part the clinical study.

Other affected individuals identified as having five or more relatives with discordant cancers will receive standard of care (SOC) multicancer panel. Families without any mutations identified (with at least a minimum of 2 members with cancer, 1 without) will be considered for additional sequencing as part of this study's primary objective of describing novel inherited cancer syndromes.

If the individual being evaluated in cancer genetics clinic (i.e. index patient) consents and their family members express interest in the study, they will move on to study visit 1. During this visit, pedigree information and medical histories will be explained, consent verified, and individual genetic counselling provided. Individuals will decide whether or not to be notified that incidental findings exist in their genomes.

Lab requisition will be done to facilitate blood draws and DNA extraction/storage and WES analysis will be completed. Any identified monogenic variants of interest will be sent to an industry partner with Clinical Laboratory Improvement Amendments (CLIA)/College of American Pathologists (CAP) certification for validation.

Study visit 2 to be completed within the next 6 months, at which any identified monogenetic variants of interest will be discussed with the participant. Those undergoing Germline High Functional Impact (gHFI) variant counting will be notified if they have more or less than the general population. Appropriate genetic counselling, recurrence risk, and additional clinical referrals will be made as necessary. Participants will be notified with a binary yes/no of any American College of Medical Genetics incidental findings and a routine clinical genetics follow-up appointment will be made

The primary objective of the study is to identify novel gene variants associated with generalized cancer susceptibility that is manifesting as a personal history of multiple primary tumors or a family history of discordant cancers. This will be done through exploratory, research grade (ie NOT CLIA/CAP certified) whole exome sequencing (WES) studies provided to patients/families with family histories of discordant cancers as an adjunct to SOC clinical genetics evaluation in order to clinically describe novel syndromic manifestations of cancer susceptibility. Suspected germline variants supporting a generalized cancer susceptibility will be further validated in a CLIA/CAP certified laboratory prior to being reported out to the patient's medical chart

Genomic Analysis of Families With a History of Discordant Cancers

Due to privacy concerns of family history and genetic information of data collected, individual participant data (IPD) will not be shared

Number of participants with a family history of 5 or more discordant cancers that have monogenic germline variants identifiable with WES sequencing

The diagnostic yield of monogenic germline variants will be calculated as the discovery rate for a monogenic pathogenic variant within each category (ie 10 pathogenic variants / 30 families = 33% yield rate).

A 2-way ANOVA will be performed, with the null hypothesis being that "family history supportive of a known syndrome versus discordant cancers does not significantly affect diagnostic yield"

Number of gHFI variants in participants with a family history of 5 or more discordant and no identified monogenic pathogenic germline variants on WES compared to population averages

Number of gHFI variants in family members within such kindreds and no cancer diagnoses will compared to those with cancer diagnoses

Diagnostic yield for monogenic germline variants in arm I (routine real-world clinical practice) vs arm II (5 or more relatives with discordant cancer diagnoses) using multicancer panels

The diagnostic yield of monogenic germline variants will be calculated as the discovery rate for a monogenic pathogenic variant within each category (ie 10 pathogenic variants / 30 families = 33% yield rate).

A 2-way ANOVA will be performed, with the null hypothesis being that "family history supportive of a known syndrome versus discordant cancers does not significantly affect diagnostic yield"

Case Comprehensive Cancer Center

Alopecia

Alopecia Areata

Hypotrichosis

Hair Diseases

Pathological Conditions, Anatomical

Participants will undergo study related assessments and the appropriate HRQoL questionnaires will be administered. Baseline and follow-up clinical assessments will be performed, preferably when the patient presents to the clinic for (clinically indicated) standard-of-care visits. Initially, these visits will be coinciding with the appropriate chemotherapy dosing cycles (as applicable to select study cohorts), and subsequently they will be performed during the standard-of-care follow-up visits.

Participants will undergo study related assessments and Medical and Personal History Questionnaire data collection forms and the appropriate HRQoL questionnaires, will be administered. Baseline and follow-up clinical assessments will be performed, preferably when the patient presents to the clinic for standard-of-care visits. Initially, these visits will be coinciding with the appropriate therapy and subsequently they will be performed during the standard-of-care follow-up visits.

Menopausal women will include unrelated visitors accompanying breast cancer patients (e.g. friends) attending the breast medicine or dermatology clinics, or female employees of MSKCC. There will be no follow-up visits (after baseline) for participants in the comparator cohort.

Clinical Assessments

Questionnaires

Alina Markova, MD

The purpose of this study is to see how many patients develop hair, skin and nail changes due to cancer treatments. The investigators would like to study the clinical factors, genetic markers, and impact on patients' health-related quality of life to learn more about who is at greater risk. We trust that the study will improve our understanding of how cancer patients feel about their skin, hair, and nail conditions. This information will help us determine the burden on breast cancer patients and survivors. It will also help us learn how to prevent these conditions and it may improve the way we treat them and counsel patients.

Study of Chemotherapy-Induced Hair Changes and Alopecia, Skin Aging and Nail Changes in Women With Non-Metastatic Breast Cancer

A Prospective, Longitudinal Study of Chemotherapy-Induced Hair Changes and Alopecia, Skin Aging and Nail Changes in Women With Non-Metastatic Breast Cancer

as assessed clinically and by phototrichogram assessments, among women exposed to cytotoxic chemotherapy

as assessed clinically and by phototrichogram assessments, among women exposed to endocrine therapies

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Pediatric Longitudinal Cohort Study of Chronic Pancreatitis	NCT03672422	Pancreatitis, C... Pancreatitis, A...	Blood sample Patient questio... Saliva sample Urine sample	0 Years - 17 Years	University of Iowa
Profiling Microbiome Associated Metabolic Pathways in Oesophageal Cancer Survivors	NCT06302660	Oesophageal Can... Quality of Life Bacterial Overg...	Breath test Saliva sample Blood sample Urine sample Stool sample Health-related ...	18 Years - 90 Years	Imperial College London
Study of Radiation Exposure and Bilateral Breast Cancer	NCT00903591	Breast Cancer	questionaire, b...	18 Years - 54 Years	Memorial Sloan Kettering Cancer Center
Improving Evidence-Based Care for Cancer Patients	NCT03207594	Head and Neck C... Prostate Cancer Breast Cancer Lung Cancer Gynecologic Can... Gastrointestina...	Survey Saliva sample Smoking Status ...	21 Years -	Medical University of South Carolina
Evaluation of Salivary RNA in Subjects Scheduled for Surgery for a Gynecologic Pathology	NCT06392997	Gynecologic Dis... Gynecologic Can... Endometriosis Ovarian Cancer Cyst Ovary Fibroid Cervical Cancer Uterine Cancer	Saliva sample	18 Years -	ZIWIG
Pediatric Longitudinal Cohort Study of Chronic Pancreatitis	NCT03672422	Pancreatitis, C... Pancreatitis, A...	Blood sample Patient questio... Saliva sample Urine sample	0 Years - 17 Years	University of Iowa
Genomic Analysis of Families With a History of Discordant Cancers	NCT04860453	Discordant Canc...	WES via Illumin... Blood Draw Skin biopsy Saliva Sample	18 Years - 100 Years	Case Comprehensive Cancer Center
Study of Chemotherapy-Induced Hair Changes and Alopecia, Skin Aging and Nail Changes in Women With Non-Metastatic Breast Cancer	NCT02530177	Non-Metastatic ...	Clinical Assess... Questionnaires Saliva sample	18 Years -	Memorial Sloan Kettering Cancer Center
Salivary Proteins in Disease and Health	NCT00100204	Diabetes Mellit... Sarcoidosis Dental Caries Sjorgren's Synd... Cystinosis Head and Neck N...		-	National Institutes of Health Clinical Center (CC)
Salivary Proteins in Disease and Health	NCT00100204	Diabetes Mellit... Sarcoidosis Dental Caries Sjorgren's Synd... Cystinosis Head and Neck N...		-	National Institutes of Health Clinical Center (CC)

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