Cancer risk and irradiation: an epidemiological and genetic study of a cohort irradiated for Tinea Capitis
Team
Sponsor
FCT
Dates and Lifetime
From: 2009-01-01 To: 2012-07-01
Duration: 42 months
Reference
PIC/IC/83154/2007
Code
CAPI
Epilation by scalp X-ray irradiation was widely used 50 years ago for treatmenting tinea capitis due to the limited pharmacological therapy. The effect of ionizing radiation was not understood at that time so X-ray irradiation was widely used for many clinical purposes. Subsequent studies showed an increase in prevalence in head and neck malignancies in the individuals subjected to this kind of intervention. Lesions more frequently found were benign and malignant thyroid disease, basal cell carcinoma (BCC) and meningioma. It was also found that the time delay between ionizing radiation exposure and tumour development can be as long as 20-40 years.
This type of treatment was also used in Portugal in the same period. Only in one Health Unit (the ancient Dispensário de Saúde e Higiene Social do Porto - DSHSP) 5358 children were submitted to such treatment and, as far as we know, no follow-up study was done in this population. Having had access to the respective files we aim to:
1. Localize, contact and provide to the irradiated individuals a clinical observation
Taking into account the work we have been doing, that allowed us to localize and observe 318 individuals (5.9% of the cohort), we hope to observe clinically at least, one third of the individuals from that original cohort. In this clinical observation a summarized clinical history is obtained and detailed examination of the head and neck area is performed, giving particular attention to thyroid palpation and skin lesions observation. To every individual without previous history of thyroid surgery, the realization of a thyroid ultrasound scan and a serum calcium determination is programed. With this procedure we intend to screen thyroid morphology and parathyroid function.
2. Evaluate the prevalence of pathology associated with head and neck irradiation, namely tumours (together with clinicians), and compare their prevalences with the data available in national data bases
Thyroid nodules, BCC and meningioma are the lesions more frequently associated with a therapeutic irradiation history so we are dedicating our efforts to screen them in our cohort. From the 318 observed individuals 4 had thyroid cancer (papillary carcinoma) representing a prevalence of 1.26 %, 18 presented BCCs (5.7%) - multiple forms of BCC in 6 out of the 18 cases (33.3%) – and 3 presented meningioma (0.94%). These figures are higher than the ones referred for non-irradiated populations and in accordance with the ones shown for irradiated cohorts.
3. Establish and organize a bank of samples from this cohort (blood, oral mucosa and tumoral tissue)
Under informed consent a blood and oral mucosa samples are being obtained for posterior DNA studies. The oral mucosa samples are being kept under -80ºC. All the blood samples are processed to obtain their DNA and are frozen a -80ºC. Whenever there is a previous head / neck surgery we try to obtain a copy of the pathology report and the paraffin embedded tissues to extract DNA from the lesion (benign or malignant) and from a normal surrounding area; all the samples are subsequently frozen. Up to the present we could obtain 21 paraffin embedded tissue samples.
4. Study genetic changes (mitochondrial and nuclear) eventually related to radiation treatment.
The DNA obtained will be used to evaluate instability/errors using repetitive DNA sequences (nuclear and mitochondrial) as markers. The mitochondrial DNA (mtDNA) deletions in blood, oral mucosa, normal and neoplasic tissue will be searched using a PCR-based technique. With the preliminary results obtained from the DNA analysis of complex rearrangements and deletions in mtDNA of 15 cases we could not get evidence that these markers can be considered as irradiation biomarkers, as the variations found in these 15 lesions studied were rare. So far we have also studied, in 12 of these cases, the Displacement-Loop (D-Loop) region, which is known to be involved in the control of both transcription and replication of mtDNA. In our series, 7 out of 12 (58.3%) of the cases showed mutations on a repetitive region of D-Loop. To confirm if these markers can be or not irradiation biomarkers we need to increase our casuistic.
We want also to evaluate the prevalence of genetic alterations in nuclear genes (oncogenes/tumor suppressor) known to be important in the tumorigenesis of the neoplasias found in the cohort (thyroid cancer, BCC and meningioma) and compare with that found in sporadic tumours: BRAF and ret-PTC in thyroid cancer; PTCH and TP53 in BCC and NF2 in meningioma.