Analysis of radiosensitivity in South African cervical and breast cancer patients

Introduction: Ionising radiation can cause DNA double strand breaks (DSB), that result in chromosomal aberrations if un- or mis-repaired. Individuals with compromised DNA damage repair mechanisms display increased chromosomal radiosensitivity. The G0-micronucleus assay (MN assay) and the γ-H2AX assay are two assays used in radiobiology to study DNA DSB and repair. Breast cancer is the leading cancer amongst South African women, with a lifetime risk of 1 in 34. Since most cancer patients in South Africa present with late-stage disease, chemotherapy and radiotherapy are commonly-used treatments. Several international studies have shown breast cancer patients to be more chromosomally radiosensitive than healthy controls. These studies have not been confirmed on a cancer population living in South Africa. Cervical cancer is the second most common cancer in South Africa; however, it is the leading cancer amongst black women with a lifetime risk of 1/35 compared to 1/82 in white women. Studies show a genetic link to cervical cancer susceptibility and DNA damage repair genes. International studies on radiation-induced DNA damage in lymphocytes of cervical cancer patients remain inconclusive and have never been performed on a South African population. Cervical cancer is caused by infection with the Human Papilloma Virus (HPV). Human Immunodeficiency Virus (HIV), HPV and cervical cancer are epidemiologically linked. Due to the high rate of HIV in South Africa, a significant proportion of cervical cancer patients receiving radiotherapy treatment will be HIV-positive. Studies show an effect of HIV on chromosomal radiosensitivity, however this has not been confirmed on a cancer population. The MN assay on the biopsies and exfoliated cervical cells of cervical cancer patients could be used as a predictive test for response to radiotherapy. The overall aim was to study chromosomal radiosensitivity in South African cervical and breast cancer patients. Materials and methods: Chromosomal radiosensitivity of lymphocytes of cervical and breast cancer patients was examined using the MN assay with the Metafer 4 of Metasystems. Different scoring methods for the Metafer system were compared to each other. The effect of HIV, HPV, ethnicity, clinical parameters and age on micronuclei (MN) values in lymphocytes was investigated. The MN assay was attempted on cells from cervical biopsies and exfoliated cervical cells. The γ-H2AX was performed on the lymphocytes of a group of cervical cancer patients. Results: A new scoring method for the Metafer 4 system that is more reliable in patients with late-stage disease was introduced. Cervical cancer patients had significantly higher MN values with HIV patients having the highest values. HPV, clinical parameters and age had a limited effect on MN values. The MN assay was unsuccessful on biopsies and exfoliated cervical cells of cervical cancer patients. There was no difference in double strand break induction and repair between cervical cancer patients and controls. In breast cancer patients, ethnicity had an effect on MN values, with only white breast cancer patients having significantly higher MN counts. Conclusion: The study showed increased chromosomal radiosensitivity in cervical cancer and white breast cancer patients. Results highlight how such studies are important within the South African context, where factors like HIV, disease stage and ethnicity can have an effect on chromosomal radiosensitivity and where unique genes/polymorphisms may play a role in cancer risk.

Grantor dc:publisher

University of the Witwatersrand. Faculty of Health Sciences

Year dc:date

2015

Author dc:creator

• Herd, Olivia Jayne

Contributors dc:contributor

• Baeyens, Ans
• Vral, Anne

• Medicine and Health Sciences
• Biology and Life Sciences

Statement dc:rights

• info:eu-repo/semantics/openAccess

Language dc:language

eng

Identifier

https://biblio.ugent.be/publication/8510804
https://biblio.ugent.be/publication/8510804/file/8510815

OAI identifier oai:identifier

oai:archive.ugent.be:8510804