Genetic Testing for Hereditary Cancer in Mexico: Insights from a Private Hospital Cohort from 2007 to 2023
Cancer Genetics and Therapeutics
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Primary Categories:
- Cancer
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Secondary Categories:
- Cancer
Introduction:
Hereditary cancer syndromes account for approximately 10% of all cancers, arising from mutations that significantly increase susceptibility to cancer development. Identifying a germline predisposition has critical implications for treatment decisions, risk-reducing interventions, and cancer screening strategies.
Traditionally, selection for genetic testing has been guided by pathological features of the cancer, age at diagnosis, family cancer history, and criteria outlined in clinical practice guidelines. However, the prevalence of germline variants in cancer predisposition genes has largely been studied in populations with access to genetic testing, often limited to 10% of the Mexican population who can afford such tests either privately or through insurance. Consequently, not all testing indications align with clinical practice guidelines, highlighting disparities in accessibility.
Methods:
A retrospective review was conducted on genetic testing data from 2007 to 2023, sourced from a private hospital in the State of Mexico, Mexico. Molecular technologies employed included targeted Sanger sequencing and next-generation sequencing (NGS), performed in laboratories worldwide.
Results:
Study Indications
Molecular Studies
From 2007, initial analyses focused on Ashkenazi founder variants. In 2017, NGS panels for hereditary cancer were introduced, initially processed in Spain. Between 2017–2019, testing in Mexico expanded to include panels covering 21–94 genes. From 2020 onward, studies were sent to Germany and included:
Findings
For patients diagnosed with cancer:
For patients with known familial variants:
Whole Exome Sequencing (WES)
Twelve WES tests were performed, primarily for pediatric patients:
Notable secondary findings:
Genetic Counseling
Pre-test counseling by a medical geneticist was conducted for 39/111 (35%) patients. Since 2022, pre-test counseling has been provided universally at no additional cost.
Conclusion:
Hereditary cancer syndromes account for approximately 10% of all cancers, arising from mutations that significantly increase susceptibility to cancer development. Identifying a germline predisposition has critical implications for treatment decisions, risk-reducing interventions, and cancer screening strategies.
Traditionally, selection for genetic testing has been guided by pathological features of the cancer, age at diagnosis, family cancer history, and criteria outlined in clinical practice guidelines. However, the prevalence of germline variants in cancer predisposition genes has largely been studied in populations with access to genetic testing, often limited to 10% of the Mexican population who can afford such tests either privately or through insurance. Consequently, not all testing indications align with clinical practice guidelines, highlighting disparities in accessibility.
Methods:
A retrospective review was conducted on genetic testing data from 2007 to 2023, sourced from a private hospital in the State of Mexico, Mexico. Molecular technologies employed included targeted Sanger sequencing and next-generation sequencing (NGS), performed in laboratories worldwide.
Results:
- Total patients: 111
- Average age: 37.2 years (range: 3 months to 81 years)
- Gender distribution: 23 men (20%), 88 women (79%)
Study Indications
- Family history of cancer: 36/111 (32%)
- Patient diagnosed with cancer: 27/111 (24%)
- Most common cancer: breast cancer (19/27, 70%; all female)
- Known familial variant: 12/111 (10%)
- Miscellaneous: 36/111 (32%)
- Included Ashkenazi ancestry, neurofibromatosis type I, tuberous sclerosis, macrocephaly, suspicious mammographic findings, etc.
Molecular Studies
From 2007, initial analyses focused on Ashkenazi founder variants. In 2017, NGS panels for hereditary cancer were introduced, initially processed in Spain. Between 2017–2019, testing in Mexico expanded to include panels covering 21–94 genes. From 2020 onward, studies were sent to Germany and included:
- Breast cancer panel (28 genes)
- Hereditary cancer panel (67 genes)
- Comprehensive cancer panel (118 genes)
- Whole exome sequencing (WES)
Findings
- Clinical relevant findings: 40/111 (36%)
- Pathogenic variants: 22/40 (55%)
- Likely pathogenic variants: 3/40 (7.5%)
- Variants of uncertain significance (VUS): 15/40 (37%)
- No clinical findings: 71/111 (64%)
For patients diagnosed with cancer:
- Pathogenic variants: 2/27 (7%)
- VUS: 4/27 (14%)
For patients with known familial variants:
- Positive findings: 8/12 (66%)
Whole Exome Sequencing (WES)
Twelve WES tests were performed, primarily for pediatric patients:
- Neurofibromatosis type 1: 6 cases (5 pathogenic variants in NF1, 1 VUS)
- Multiple enchondromas: 1 case (pathogenic variant in EXT1)
- Macrocephaly and hypotonia: 1 case (pathogenic variant in PTEN)
- Tuberous sclerosis: 1 case (pathogenic variant in TSC2)
Notable secondary findings:
- A 3-year-old female with autism (pathogenic BRCA1 variant inherited maternally)
- A 33-year-old male with obstructive azoospermia (pathogenic variants in CFTR and BRCA2)
Genetic Counseling
Pre-test counseling by a medical geneticist was conducted for 39/111 (35%) patients. Since 2022, pre-test counseling has been provided universally at no additional cost.
Conclusion:
- Pathogenic and likely pathogenic variants were identified in 23% of patients, similar to populations with universal genetic testing access.
- Molecular testing for hereditary cancer in Mexico has evolved in step with global advancements, starting with single-gene analyses (e.g., BRCA1/2) to expanded NGS panels.
- Access to genetic testing remains limited, with only 10% of the Mexican population able to afford testing. This creates a reliance on family cancer history for study indication, even when the index patient cannot access testing due to financial constraints.
- Universal access to genetic testing should be prioritized, even for patients without a family cancer history, to ensure equitable healthcare.
- Establishing a database of genetic variants in cancer predisposition genes could aid in the reclassification of the numerous VUS reported in non-Caucasian populations, such as Mexicans.