LUNG CANCER AND PULMONARY TUBERCULOSIS -A COMPARATIVE POPULATION-GENETIC STUDY Pešut DP1,2,*, Marinkovic DM3 *Corresponding Author: Dragica P. Pešut, Institute of Lung Diseases and Tuberculosis, Research
and Epidemiology Department, Visegraska 26/20, 11000 Belgrade, Serbia; Tel.: +381-11-361-
5561; Fax: +381-11-268-1591; E-mail: dragica.pesut@gmail.com page: 45
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DISCUSSION
This study showed a statistically significant difference of the middle values of genetic homozygosity, differences in the type of distribution and of the presence of certain individual combinations of such traits. Significantly decreased HRC number in both patients' groups could be a manifestation of their decreased degree of homozygosity and might support dominant factor influence in predisposition to TB and to LC. While the molecular genetic research on Moroccan multiplex families supports this for TB [21], a new research on MDM2 promoter polymorphisms as associated risk for LC showed contradiction to previous reports [8]. The results of our study, together with previous research based on the same methodology, show that any retreat from optimal homozygos-ity degree, whether decrease or increase, points to the possibility of changed genetic-physiological organism homeostasis and its altered reaction norm that leads to illness [17,25,27-31]. Namely, apart from LC and TB, decreased homozygousity was found in asthma, acute appendicitis, while increased homozy-gosity level has been shown in diabetes mellitus, congenital hip dislocation and Balkan endemic neph-ropathy, to mention just a few [17,25,27-31]. Recent direct molecular evidence that TB involves a genetic component of at least one major locus with a dominant susceptibility allele, also support our findings [21]. While in the mentioned study, a decrease of logarithm of the odds (LOD) score for TB was found in the 19p12 gene location, previously connected to blue eye color, a new research of a Dutch group indicated that 15q13.1 was the predominant region involved in human iris color [26]. This latter could bring a new light to our earlier finding that eye color and hair color in TB patients have a characteristic expression and independent inheritance, which might make closer the particular genome region responsible for TB susceptibility [17]. The new eye color location also correlates with the finding of a locus at 15q11-q13 (OMIM number 300259) for susceptibility to TB. Only interdisciplinary approach could make it possible to put into connection eye color-related findings aimed to improve forensic analysis to the important field of susceptibility to TB. Similarly, while epidemiologic and clinical studies connected TB with diabetes mellitus long ago, susceptibility regions at 2q34-2q36.2 have been associated with TB and diabetes mellitus [23].
We found significantly decreased O blood type in TB patients. Numerous studies have shown the frequency of ABO blood types differ in groups of patients or subjects [13,17,28]. We assume that certain connection between a predisposition to TB and some of the ABO blood types exists, and this is in correlation with the previous findings [14,17]. Our study on associated diseases showed significantly decreased number of palatal tonsillectomies in both LC and TB patients, increased the average age at tonsillectomy in LC patients compared to controls, and decreased frequency of allergic diseases in the LC group [34]. Both the mentioned results on independent genetic markers in LC and TB need further investigation with a larger sample size and multi center multi disciplinary research.
There were possible limitations in our study such as the list and number of chosen HRCs and their correct identification in the examined persons. The list of traits was developed as the result of the experiences of the authors of the HRCs test in its previous application in several other studies [27-31]. Since 23 homo-recessive traits were analyzed in each individual, both in patients groups and controls, this multiplied the total number of tested traits to 4,600 in total, and influenced the statistical power of the test. Thus, even a smaller number of patients and controls would be sufficient in this kind of investigation. When it comes to possible errors generated by subjectively different identification of the traits, it has been taken to a minimum having only one person to detect them in all the examinees.
Although enormous efforts to find out a single dominant factor both in LC and TB have been done, especially during the last decade, it is more probable that not a single gene but a pleiotropic effect of few (many) plays a role in development of these diseases. The results of our study, according to i) HRCs average number, ii) gene allele frequencies, iii) total cumulative x2 difference, and iv) frequency distribution, showed that both patients' groups present different samples when compared to healthy controls, according to their population-genetic structure. That means that persons in these groups may give a different response to similar environmental agents when compared to healthy ones. The population-genetic approach in this comparative analysis may serve as paradigm of successful cooperation between clinicians, epidemiologists and laboratory scientists in the pursuit of the understanding of cancer etiology and predisposition, and susceptibility to TB in humans. The described methodology can be used in further improved analyses, with hope that it can be applied in as an early prognosis for susceptibility to a variety of diseases.
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