Family history of cancer and non-malignant diseases and risk of childhood acute lymphoblastic leukemia: A Children's Oncology Group Study

Abstract Background Hereditary cancer susceptibility syndrome (HCSS) contributes to the cancer predisposition at an early age, therefore, identification of HCSS has found to be crucial for surveillance, managing therapeutic interventions and refer the patients and their families for genetic counselling. The study aimed to identify ALL patients who meet the American College of Medical Genetics (ACMG) criteria and refer them for the genetic testing for HCSS as hereditary leukemia and hematologic malignancy syndrome, and to elucidate the significance of high consanguinity with the prevalence of inherited leukemia in Pakistani population. Methods A total of 300 acute lymphoblastic leukemia patients were recruited from the Children’s Hospital, Lahore, Pakistan from December 2018 to September 2019. A structured self-reporting questionnaire based on family and medical history of the disease was utilized for the data collection. Results In our cohort, 60.40% of ALL patients were identified to meet ACMG criteria. Among them, a large number of patients (40.65%) solely fulfil the criteria due to the presence of parental consanguinity. However, parental consanguinity showed protective impact on the onset at early age of disease [OD = 0.44 (0.25–0.77), p-value = 0.00] while, a family history of cancer increased the risk of cardiotoxicity [OD = 2.46 (1.15–5.24), p-value = 0.02]. Parental consanguinity shows no significant impact on the family history of cancer and the number of relatives with cancer. Conclusions More than 50% of the ALL patients were considered the strong candidates’ for genetic testing of HCSS in the Pakistani population, and parental consanguinity was the leading criteria fulfilled by the individuals when assessed through ACMG guidelines. Our study suggests revisiting ACMG guidelines, especially for the criterion of parental consanguinity, and formulating the score based criteria based on; genetic research, the toxicology profile, physical features, personal and family history of cancer for the identification of patients for the genetic testing.

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Prevalence of Hereditary Cancer Susceptibility Syndromes (HCSS) in Acute Lymphoblastic Leukemia (ALL): A Cross-Sectional Study in a Highly Consanguineous Population.

10.21203/rs.3.rs-133503/v1 ◽

2021 ◽

Author(s):

Sara Aslam ◽

Shabana NA ◽

Mehboob Ahmed

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Family History ◽

Genetic Counselling ◽

Cancer Susceptibility ◽

Lymphoblastic Leukemia ◽

P Value ◽

Early Age ◽

Parental Consanguinity ◽

History Of ◽

History Of Cancer

Abstract Background: Hereditary cancer susceptibility syndrome (HCSS) has been reported to impact cancer predisposition at an early age, therefore, identification of HCSS has found to be crucial for surveillance, managing therapeutic interventions and referring the patients and their families for genetic counselling. The aims of this study are to assess the prevalence of HCSS as hereditary leukemia and hematologic malignancy syndrome by using ACMG guidelines and to assess parental consanguinity as the criterion for referring patients for the genetic counselling. Methods: A total of 300 acute lymphoblastic leukemia subjects were recruited from the Children’s Hospital, Lahore, Pakistan during the period of December 2018 to September 2019. Structured self-reporting questionnaire based on family and medical history of the disease was utilized for the data collection.Results: In our cohort, 60.40% of ALL patients were identified to have HCSS and among them 40.65% patients solely fulfil the criteria due to the presence of parental consanguinity. Parental consanguinity was shown to have protective impact on the onset at early age of disease [OD=0.44 (0.25-0.77), p-value= 0.00] while family history of cancer increase the risk of cardiotoxicity [OD= 2.46 (1.15-5.24), p-value=0.02]. Parental consanguinity in the population shows no significant impact on the family history of cancer and the number of relatives with cancer. Conclusions: The higher prevalence of HCSS in Pakistani population is attributed to the presence of parental consanguinity in more than 50% of the patients when assessed through ACMG guidelines. Our study suggests revisiting ACMG guidelines for the criterion of parental consanguinity in the highly consanguineous population and formulating the score based criteria for the identification of inherited ALL for genetic counselling.

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