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      MMP1-1607(1G>2G) polymorphism and the risk of lung cancer in Lebanon

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          Abstract

          CONTEXT:

          Matrix metalloproteinases (MMPs) are a family of enzymes that degrade various components of the extracellular matrix and are involved in the development and progression of cancer. Lung cancer is the most commonly diagnosed cancer in Lebanon. MMP1 is responsible for degrading stromal collagens, which enhance the ability of neoplastic cells to cross basal membrane of both the endothelium and the vascular endothelium. A recent meta-analysis has suggested that the MMP1-1607 2G allele may be associated with an increased risk for certain types of cancers.

          AIM:

          This study was undertaken to investigate the association between guanine insertion polymorphism in the MMP1 promoter and the susceptibility to lung cancer in the Lebanese population.

          SETTINGS AND DESIGN:

          This case-control study was conducted on 41 patients with lung cancer and 51 age-matched healthy controls, recruited from different regions of Lebanon.

          METHODS:

          Cases were histologically confirmed lung cancer patients obtained from different hospitals in Lebanon. Controls were healthy unrelated individuals with no history of cancer or genetic diseases. All subjects were genotyped for MMP1 -1607(1G>2G) polymorphism using polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP).

          RESULTS:

          No statistically significant differences were found when genotype and allele distribution of MMP1 -1607(1G>2G) polymorphism were compared between patients with lung cancer and controls [ P= 0.6 by chi-squared test on a 3×2 contingency table; allelic P=0.61, OR (95% CI) = 1.18 (0.60-2.31)].

          CONCLUSION:

          Our data shows that MMP1 promoter polymorphism is not associated with lung cancer susceptibility in the Lebanese population.

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          Most cited references13

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          Polycyclic aromatic hydrocarbons, carbon monoxide, "tar", and nicotine in the mainstream smoke aerosol of the narghile water pipe.

          A smoking machine protocol and yields for "tar", nicotine, PAH, and CO are presented for the standard 171-puff steady periodic smoking regimen proposed by Shihadeh et al. [Shihadeh, A., Azar, S., Antonios, C., Haddad, A., 2004b. Towards a topographical model of narghile water-pipe cafe smoking: A pilot study in a high socioeconomic status neighborhood of Beirut, Lebanon. Pharmacology Biochemistry and Behavior 79(1), 75]. Results show that smokers are likely exposed to more "tar" and nicotine than previously thought, and that pyronsynthesized PAH are present in the "tar" despite the low temperatures characteristic of the tobacco in narghile smoking. With a smoking regimen consisting of 171 puffs each of 0.53l volume and 2.6s duration with a 17 s interpuff interval, the following results were obtained for a single smoking session of 10 g of mo'assel tobacco paste with 1.5 quick-lighting charcoal disks applied to the narghile head: 2.94 mg nicotine, 802 mg "tar", 145 mg CO, and relative to the smoke of a single cigarette, greater quantities of chrysene, phenanthrene, and fluoranthene. Anthracene and pyrene were also identified but not quantified. The results indicate that narghile smoke likely contains an abundance of several of the chemicals thought to be causal factors in the elevated incidence of cancer, cardiovascular disease and addiction in cigarette smokers.
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            Interstitial collagenases as markers of tumor progression.

            Degradation of the extracellular matrix is the sine qua non of tumor invasion and metastasis. Most of this degradation is mediated by matrix metalloproteinases (MMPs), a family of enzymes that, collectively, degrades the extracellular matrix. Although the basement membrane-degrading enzymes, MMP-2 and MMP-9, have been given considerable attention for their roles in invasion and metastasis, the interstitial collagenases, a subfamily of MMPs that cleaves the stromal collagens types I and III, have received relatively little recognition for their part in these processes. This subfamily is comprised of collagenase 1 (MMP-1), collagenase 3 (MMP-13), and the MT-MMPs, membrane-bound MMPs, and numerous reports over the last several years document the expression of these MMPs in a wide variety of advancing tumors. Of particular interest is a single nucleotide polymorphism in the MMP-1 promoter that increases the transcription of this gene and that is associated with melanoma and with ovarian and endometrial cancers. The collagenases can mediate tumor invasion through several mechanisms, which include constitutive production of enzyme by the tumor cells, induction of collagenase production in the neighboring stromal cells, and interactions between tumor/ stromal cells to induce collagenase production by one or both cell types. Thus, evidence indicates that elevated expression of the interstitial collagenases is associated with a poor prognosis in a variety of cancers, and therefore, these MMPs can serve as a marker of tumor progression.
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              Charcoal emissions as a source of CO and carcinogenic PAH in mainstream narghile waterpipe smoke.

              Burning charcoal is normally placed atop the tobacco to smoke the narghile waterpipe. We investigated the importance of charcoal as a toxicant source in the mainstream smoke, with particular attention to two well-known charcoal emissions: carbon monoxide (CO) and polyaromatic hydrocarbons (PAH). CO and PAH yields were compared when a waterpipe was machine smoked using charcoal and using an electrical heating element. The electrical heating element was designed to produce spatial and temporal temperature distributions similar to those measured using charcoal. With a popular type of ma'assel tobacco mixture, and using a smoking regimen consisting of 105 puffs of 530ml volume spaced 17s apart, it was found that approximately 90% of the CO and 75-92% of the 4- and 5-membered ring PAH compounds originated in the charcoal. Greater than 95% of the benzo(a)pyrene in the smoke was attributable to the charcoal. It was also found that the relative proportions of individual PAH species, the "PAH fingerprint", of the mainstream smoke were highly correlated to those extracted from the unburned charcoal (R(2)>0.94). In contrast, there was no correlation between the PAH fingerprint of the electrically heated and charcoal-heated conditions (R(2)<0.02). In addition to inhaling toxicants transferred from the tobacco, such as nicotine, "tar", and nitrosamines, waterpipe smokers thus also inhale large quantities of combustion-generated toxicants. This explains why, despite the generally low temperatures attained in the narghile tobacco, large quantities of CO and PAH have been found in the smoke.
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                Author and article information

                Journal
                Ann Thorac Med
                Ann Thorac Med
                ATM
                Annals of Thoracic Medicine
                Medknow Publications & Media Pvt Ltd (India )
                1817-1737
                1998-3557
                Jul-Sep 2012
                : 7
                : 3
                : 130-132
                Affiliations
                [1] Department of Basic Sciences, King Saud bin Abdulaziz University for Health Sciences, Riyadh, KSA
                [1 ] Department of Biological and Environmental Sciences, Faculty of Science, American University of Beirut Medical Center, Beirut, Lebanon
                [2 ] Department of Pharmacology, Faculty of Pharmacy, American University of Beirut Medical Center, Beirut, Lebanon
                [3 ] Department of Internal Medicine, Clinical Research Institute, American University of Beirut Medical Center, Beirut, Lebanon
                [4 ] Department of Biological and Environmental Sciences, Faculty of Science, Beirut Arab University, Beirut, Lebanon
                Author notes
                Address for correspondence: Dr. Hana Fakhoury, Department of Basic Sciences, University Pre-Professional Program, King Saud bin Abdulaziz University for Health Sciences, Riyadh, KSA. E-mail: hana.fakhoury@ 123456gmail.com
                Article
                ATM-7-130
                10.4103/1817-1737.98844
                3425043
                22924069
                af10b023-aa9e-415c-97d8-5555afc98d64
                Copyright: © Annals of Thoracic Medicine

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 11 March 2012
                : 24 April 2012
                Categories
                Original Article

                Respiratory medicine
                mmp1,polymorphism,lebanon,lung cancer
                Respiratory medicine
                mmp1, polymorphism, lebanon, lung cancer

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