What you should know about Genes and Cancer…

1. Hereditary cancer syndrome is a genetic predisposition to certain cancers, due to mutations in one or more genes.

2. Mutations are changes in DNA sequences.

3. Most common hereditary cancer syndrome is Breast and Ovarian cancer syndrome.

Hereditary Breast and Ovarian Cancer Syndrome (HBOC)*

1. High risk of breast and ovarian cancers, male breast cancer, prostate cancer, pancreatic cancer, and melanoma.

2. Individuals with HBOC tend to develop cancer at an earlier age than the general population, and have higher risk for bilateral breast cancer, a second primary tumor in a different tissue, and cancer recurrence.

3. Although, most commonly attributed genes are BRCA1&2, HBOC susceptibility genes also include CDH1, PALB2, PTEN, TP53 among others.

*At CARINGdx, we offer a 20+ gene HBOC panel (100% NCCN coverage), which includes customized hereditary breast, ovarian, prostate and pancreatic cancer panels

Lifetime cancer risks associated with BRCA1 & BRCA2
Can your cancer be hereditary? Risk factors… (As per NCCN guidelines)

Breast Cancer Age <45yrs at diagnosis Age 46-50yrs at diagnosis with unknown family history Second breast cancer Blood relative (1 or more) with breast, ovarian, pancreatic or prostate cancer Age <60yrs at diagnosis with Triple Negative Breast cancer Bilateral Breast cancer Male Breast Cancer Ovarian Cancer Any Age Epithelial or non-mucinous histology Pancreatic Cancer Any Age Exocrine Pancreatic cancer Blood relative with exocrine pancreatic cancer\ Prostate Cancer Metastatic Any age High-Grade Blood relative (1 or more) with breast, ovarian, pancreatic or prostate cancer

Hereditary / Familial Colorectal Cancer Panel & Endometrial Cancer Panel*

High risk of colorectal cancer and endometrial cancer. The syndromes in hereditary colorectal cancer (HCC) and hereditary endometrial cancer (HEC) are: Hereditary Non-polyposis Colorectal Cancer (HNPCC) Lynch Syndrome (LS)* Hereditary Polyposis Colorectal Cancer (HPCC) Syndromes Familial Adenomatous Polyposis (FAP/AFAP) Peutz-Jeghers Syndrome (PJS) Juvenile Polyposis Syndrome (JPS) Cowden Syndrome / PTEN Hamartoma Tumor Syndrome Li-Fraumeni Syndrome *Lynch syndrome is strongly linked to colorectal cancer and endometrial cancer. Women with Lynch syndrome tend to get endometrial cancer 10 to 20 years earlier than the women without having inherited risk. *At CARINGdx, we offer customized HNPCC panel for colorectal cancer and endometrial cancer (100% NCCN coverage)

Lifetime cancer risks associated with various syndromes of HCC
Can your cancer be hereditary? Risk factors… (As per NCCN guidelines)

Colorectal Cancer A person diagnosed with colorectal cancer diagnosed before age 50 A person having synchronous or metachronous colorectal cancer or other hereditary nonpolyposis colorectal cancer related tumor, regardless of age A person younger than 60 years of age exhibiting tumor-infiltrating lymphocytes A person with colorectal cancer at any age, and, colorectal cancer or hereditary nonpolyposis colorectal cancer related tumor diagnosed before the age of 50 years in at least one first-degree relative A person with colorectal cancer at any age, and, colorectal cancer or hereditary nonpolyposis colorectal cancer related tumor diagnosed before the age of 50 years in two or more first- or second-degree relatives https://www.nature.com/articles/gim2013166 Endometrial Cancer Patients with endometrial or colorectal cancer with the following history: A female patient with at least three relatives with a Lynch/HNPCC-associated cancer (colorectal, endometrial, small bowel, ureter, or renal pelvis) in one lineage One affected individual should be a first-degree relative of the other two At least two successive generations should be affected At least one Lynch/HNPCC-associated cancer should be diagnosed before age 50. A female patient with synchronous or metachronous endometrial and colorectal cancer with the first cancer diagnosed prior to age 50 A female patient with synchronous or metachronous ovarian and colorectal cancer with the first cancer diagnosed prior to age 50 A female patient with colorectal or endometrial cancer with evidence of a mismatch repair defect (i.e., microsatellite instability (MSI) or immunohistochemical loss of expression of MLH1, MSH2, MSH6, or PMS2) A female patient with a first- or second-degree relative with a known mismatch repair gene mutation

Why do you need these tests…
Clinical Exome

More stringent screening protocols (Early detection~Secondary prevention) – As per NCCN guidelines Risk of a second cancer (based on the gene mutation) Risk of cancer in other blood relatives Risk Reducing Interventions Only if advised by the clinician Potential therapeutic options As per the clinician’s discretion

How are these tests done…

A peripheral blood sample is taken (just like any routine blood test), and DNA is extracted. The DNA is then sequenced using Next-Generation sequencers and any deviations from normal (variants) are then analyzed for their clinical significance and any significant deviations are reported.

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