| Sažetak | Hipodoncija je jedna od najčešćih kongenitalnih anomalija u ljudi. Odontogeneza je složen embrionalni proces reguliran s više od 300 gena, čija mutacija može uzrokovati nedostatak zubnog zametka. Geni koji reguliraju razvoj zuba također igraju značajnu ulogu u razvoju drugih tjelesnih sustava i organa. Dosadašnja istraživanja pokazala su da karcinom dojke, karcinom ovarija, kolorektalni karcinom i karcinom pluća dijele isti genetski put uzročnosti s hipodoncijom, dok povezanost hipodoncije i karcinoma štitnjače još nije istražena. Prevalencija papilarnog karcinoma štitnjače jedna je od najbrže rastućih prevalencija karcinoma te predstavlja ozbiljan javnozdravstveni problem među ženama. Cilj ovog istraživanja bio je utvrditi učestalost pojave ageneze zuba kod ispitanica s dijagnosticiranim papilarnim karcinom štitnjače (PTC). Istraživanje se sastojalo od kliničkog pregleda, uzimanja stomatološke, medicinske i obiteljske anamneze, očitavanja ortopantomograma, očitavanja nalaza patohistološke dijagnoze (PHD), očitavanja postoperativnog nalaza scintigrafije jodom -131 i očitavanja postoperacijskih kliničkih parametara tumorskog biljega tireoglobulina (Tg) i antitireoglobulinskih antitijela ( antiTg). Stopa prevalencije hipodoncije bila je 11,3 % u pokusnoj skupini i 3,5 % u kontrolnoj skupini. Prevalencija hipodoncije, mikrodoncije i palatinano postavljenog očnjaka pokazala se statistički značajno veća u žena s papilarnim karcinom štitnjače nego u kontrolnoj skupini. Eksperimentalna skupina pokazala je veću prevalenciju dentalne ageneze gornjih lateralnih sjekutića, donjih lijevih centralnih sjekutića, svih trećih kutnjaka osim gornjeg lijevog u odnosu na prevalenciju navedenih zuba u kontrolnoj skupini. Žene s PTC-om pokazale su značajno veću prevalenciju PDC-a od kontrolne skupine (3,5 %, 0,7 %, P = 0,002). Vjerojatnost hipodoncije kao kliničkog nalaza povećava se 2,6 puta, a mikrodoncije 7,7 puta u žena s PTC-om. Rezultati ukazuju na potencijalnu vezu između dva fenotipa, odontogeneze i papilarnog karcinoma štitnjače. Trajni nedostatak zub može poslužiti kao faktor rizika za PTC u žena. Budući da je idealno vrijeme za prvi ortopantomografski rendgenski snimak u dobi od 7 godina, bilo bi lako identificirati žene s većim rizikom razvoja PTC-a. |
| Sažetak (engleski) | Tooth development is under strict genetic control with more than two hundred identified genes responsible for its development. Tooth development is under strict genetic control with more than two hundred identified genes responsible for its development. Genes associated with early tooth morphogenesis also have developmental regulatory functions in other
organs. Genetics have been found to play a role in dental anomalies at various levels. Numerous authors have investigated whether a gene error causes various phenotypic disorders such as anomalies in teeth' number, shape and position. Defective genes interacting with each other or acting alone in combination with other genes produce a specific phenotype and cause tooth agenesis. Over the past few decades, significant efforts have been made to identify gene loci that cause the most common developmental anomalies in humans. Non-syndromic hypodontia is most often associated with changes in the AXIN2, MSX1, and PAX9 genes. It has been observed that hypodontia, microdontia, and palatally dislocated canine (PDC) share a close and strong genetic link and that these congenital abnormalities are associated with numerous mutations in genes related to transcription factors and growth factors involved in tooth development. Many studies indicate a strong genetic connection between carcinogenesis and dental agenesis. Research has shown that the genes AXIN2, EDA, FGF3, FGFR2, FGFR10, WNT10A, MSX1, and PAX9 are directly related to dental agenesis and the development of
cancer. Bond's research suggests a genetic link between ovarian cancer and hypodontia. AXIN2, MSX1, PAX9, WNT10A, EDA, BARX and BRCA1 genes may contribute to hypodontia and carcinogenesis. That study provided evidence that half of the patients with the two conditions were independently caused, which significantly reduced the previously estimated risk of ovarian cancer for women with asymptomatic hypodontia. Thyroid cancer is the most common malignancy of the female hormonal system with a significantly increasing incidence and one of the fastest growing in the US compared to other
cancers in the last 20 years. Papillary thyroid cancer (PTC) is histologically the most common category of thyroid cancer and accounts for 85% of all thyroid cancers. Liu et al. in 2016. showed that the AXIN2 polymorphism has a significant relationship with PTC. The finding of Lv and Xue suggest proteins that cause rapid progression of PTC by inhibiting Wnt/-catenin and activating the Axin2 gene. To our knowledge, a review of the literature indicates a lack of research on the correlation between hypodontia and PTC.
Aim: The research aimed to determine the occurrence and pattern of tooth agenesis, microdontia, and palatally displaced canine (PDC) in women with diagnosed papillary thyroid cancer (PTC) compared to a control group of women without any malignancy or thyroid disease. The study's objective is to ascertain the following in participants with papillary thyroid cancer: 1) frequency of tooth agenesis, 2) the number of missing teeth, 3) which teeth are most often missing, 4) whether tooth agenesis occurs unilaterally or bilaterally, 5) does tooth agenesis occur more often in the maxilla or mandible, 6) does tooth agenesis occur more often unilaterally or bilaterally, 7) whether tooth agenesis occurs more often in the front or back part of the dental arch, 8) frequency of microdontia, 9) frequency of tooth impaction, 10) does exposure to diagnostic radiation (such as MR, CT or multiple x-rays of the head, neck, lungs, limbs) in childhood and early life affect the appearance of tooth agenesis.
Materials and methods: By examining the patient database of the Reference Center for Thyroid Diseases, the Oncology and Nuclear Medicine Clinic of the Sisters of Mercy Clinical Hospital Center, a sample of 116 women was selected. Including criteria for the experimental group were: 1) female gender, 2) diagnosis of papillary thyroid cancer, and 3) age 20 to 40 years. Excluding criteria for the experimental group were: 1) diagnosis of another malignant disease, 2) craniofacial abnormalities, 3) cleft palate and/or lip syndromes, 4) ectodermal dysplasia, 5) prosthetic replacements, 6) inability to determine with certainty the reason for tooth loss. The control group consists of 424 women without a diagnosed malignant disease, aged 20 to 40, randomly selected from the population with the condition that they have an orthopantomogram recorded. The exclusion criteria for the control group were: 1) diagnosis of malignant disease, 2) diagnosis of autoimmune disease, 3) diagnosis of endocrine disease, 4) craniofacial abnormalities, 5) cleft palate and/or lip syndromes, 6) ectodermal dysplasia,7) positive family history of malignant disease, 8) positive family history of autoimmune disease, 9) radiation or chemotherapy in childhood, 10) prosthetic replacements and 11) inability to determine with certainty the reason for tooth loss. From the dental status, it was detected: 1) absence of embryos of permanent teeth including teeth 18, 28, 38, 48, 2) absence of a permanent tooth caused by extraction, and 3) microdontia in the permanent dentition. From the dental anamnesis and dental documentation, data on: 1) previous orthodontic therapy, 2) localization of tooth impaction if it existed on teeth 13 and 23, 3) surgical tooth extractions, 4) presence of periodontal diseases (gingivitis, periodontitis), 5) existence of subjective disturbances in the oral cavity (dryness, burning, loss of taste). Orthopantomogram analysis confirmed the lack of permanent tooth germ and the presence of tooth impaction 13, 23, 18, 28, 38, 48. Information about exposure to multiple diagnostic radiations in childhood (MR, CT, or multiple X-ray imaging of the head, neck, lungs, and limbs), the existence of a chronic disease, and the existence of an autoimmune disease was taken from the medical anamnesis. The following data were used in the research from the medical documentation made at the Oncology and Nuclear Medicine Clinic of the KBC Sisters of Mercy: 1) tumor type according to TNM tumor classification based on the findings of pathohistological diagnosis (PHD), 2) tumor type according to the recent WHO (2017) classification of thyroid tumors based on the histological picture of PHD findings, 3) status post radiotherapy cum I -131 -3441 MBq (93 mCi), 4) type of surgery the subject underwent (non-operated, thyroidectomia totalis, dissectio colli), 5) postoperative clinical parameters of the tumor marker thyroglobulin (Tg) and anti-thyroglobulin antibodies (anti-Tg), 6) status of postoperative scintigraphy of the whole body with iodine-131 (postoperative remnant in the thyroid gland/pathological accumulation in the neck/distant metastases). Information was
taken from the family history about the existence of malignant and autoimmune diseases in the closest relatives (mother, father, grandmother, grandfather, brothers, and sisters of the mother and father) diagnosed at an age younger than 65 years.
Results: The research sample consisted of 116 women diagnosed with papillary thyroid cancer (PTC) in the experimental group and 424 women in the control group, in the age range of 20 to 40 years. The median age of the participants was 30 years (interquartile range, IQR, 26 - 36) in the experimental group, while it was 31 years (IQR 24 - 35) in the control group.
A positive family history of malignant diseases in the closest relatives (mother, father, grandmother, grandfather, brothers, and sisters of the mother and father) diagnosed at an age younger than 65 was reported by 62 respondents (53.5%). The results of the regression analysis of the relationship between the characteristics of papillary thyroid cancer (TNM classification, type of surgery the patient underwent, radiotherapy status, postoperative whole-body scintigraphy status, postoperative clinical parameters of the tumor marker Tg and anti-Tg, multiple exposures to diagnostic radiation and childhood and the occurrence of cancer in close relatives) and hypodontia show that there is no connection between cancer parameters and the incidence of hypodontia. The prevalence of hypodontia, microdontia, and PDC was statistically higher in women with PTC than in the control group. The prevalence rate of hypodontia was 11.3 % in the experimental group and 3,5% in the control group. The experimental group showed a higher prevalence of dental agenesis of upper lateral incisors, lower left central incisors, all the third molars except the upper left over the prevalence of mentioned teeth in the control group. Women with PTC showed the prevalence of PDC significantly higher than the control group (3,5 %, 0,7 %, P = 0.002). The probability of hypodontia as a clinical finding increases 2.6 times, and microdontia 7.7 times in women with PTC.
Conclusion: The results of this research point to the following conclusions: 1) the lack of a permanent tooth can serve as an early indicator of the possible occurrence of PTC, as it increases the probability 2.6 times, 2) the prevalence of hypodontia is statistically significantly higher in the experimental group than in the control group, 3) the prevalence of microdontia is
statistically significantly higher in the experimental group than in the control group, 4)the occurrence of PDC shows higher values in the experimental group, 5) there is a strong association between microdontia of the upper lateral incisor and agenesis of the lower left incisor, 6) there is a strong association between upper lateral incisor microdontia and PDC, 7)
there is a higher prevalence of bilateral upper second incisor agenesis in the experimental group than in the control group, 8) the most affected teeth were the upper lateral incisors, then the lower 2nd premolars and the lower left incisors in the experimental group, while in the control group the 2nd premolars were most affected, 9) tooth agenesis was found more often in the mandible (55.55%) than in the maxilla (44.44%). Since the ideal age for the first orthopantomographic x-ray is 7 years, we to identify women who are at a higher risk of developing papillary thyroid cancer early with a simple and inexpensive diagnostic test, profile them and enable quality medical monitoring from an early age and prevent the disease from being detected in an already advanced stage. The research showed that parameters such as tumor size and the existence of regional metastases are not correlated with the appearance of tooth agenesis. This research can serve as a basis for further research on more aggressive cancers whose genetics of carcinogenesis have points of contact with the genetics of tooth agenesis, such as endometrial cancer. |
