AIMS: Cholinergic signaling, particularly in response to non-physiological ligands like nicotine, stimulates carcinogenesis of a variety of tissue types including epithelia of the cervix uteri. Cholinergic signaling is mediated by nicotinic acetylcholine receptors (nAChRs), which are pentamers formed by subsets of 16 nAChR subunits. Recent literature suggests that single nucleotide polymorphisms (SNPs) of some of these subunits, notably alpha5, are risk factors for developing lung cancer in smokers as well as in non-smokers. MAIN METHODS: We have studied the prevalence of four SNPs in the alpha5, alpha9, and beta1 subunits, which are expressed in cervical cells, in 456 patients with cervical cancers, precursor lesions, and healthy controls from two cohorts in Mexico. KEY FINDINGS: A SNP in the alpha9 subunit, the G allele of rs10009228 (alpha9, A>G) shows a significant trend in the combined cohort, indicating that this allele constitutes a risk factor for neoplastic progression. The A allele of the SNP rs16969968 (alpha5, G>A), which correlates with the development of lung cancer, shows a non-significant trend to be associated with cervical lesions. Two other SNPs, rs55633891 (alpha9, C>T) and rs17856697 (beta1, A>G), did not exhibit a significant trend. SIGNIFICANCE: Our study points to a potential risk factor of cervical carcinogenesis with importance for DNA diagnosis and as a target for intervention.
AIMS: Cholinergic signaling, particularly in response to non-physiological ligands like nicotine, stimulates carcinogenesis of a variety of tissue types including epithelia of the cervix uteri. Cholinergic signaling is mediated by nicotinic acetylcholine receptors (nAChRs), which are pentamers formed by subsets of 16 nAChR subunits. Recent literature suggests that single nucleotide polymorphisms (SNPs) of some of these subunits, notably alpha5, are risk factors for developing lung cancer in smokers as well as in non-smokers. MAIN METHODS: We have studied the prevalence of four SNPs in the alpha5, alpha9, and beta1 subunits, which are expressed in cervical cells, in 456 patients with cervical cancers, precursor lesions, and healthy controls from two cohorts in Mexico. KEY FINDINGS: A SNP in the alpha9 subunit, the G allele of rs10009228 (alpha9, A>G) shows a significant trend in the combined cohort, indicating that this allele constitutes a risk factor for neoplastic progression. The A allele of the SNP rs16969968 (alpha5, G>A), which correlates with the development of lung cancer, shows a non-significant trend to be associated with cervical lesions. Two other SNPs, rs55633891 (alpha9, C>T) and rs17856697 (beta1, A>G), did not exhibit a significant trend. SIGNIFICANCE: Our study points to a potential risk factor of cervical carcinogenesis with importance for DNA diagnosis and as a target for intervention.
Authors: Christopher I Amos; Xifeng Wu; Peter Broderick; Ivan P Gorlov; Jian Gu; Timothy Eisen; Qiong Dong; Qing Zhang; Xiangjun Gu; Jayaram Vijayakrishnan; Kate Sullivan; Athena Matakidou; Yufei Wang; Gordon Mills; Kimberly Doheny; Ya-Yu Tsai; Wei Vivien Chen; Sanjay Shete; Margaret R Spitz; Richard S Houlston Journal: Nat Genet Date: 2008-04-02 Impact factor: 38.330
Authors: Rayjean J Hung; James D McKay; Valerie Gaborieau; Paolo Boffetta; Mia Hashibe; David Zaridze; Anush Mukeria; Neonilia Szeszenia-Dabrowska; Jolanta Lissowska; Peter Rudnai; Eleonora Fabianova; Dana Mates; Vladimir Bencko; Lenka Foretova; Vladimir Janout; Chu Chen; Gary Goodman; John K Field; Triantafillos Liloglou; George Xinarianos; Adrian Cassidy; John McLaughlin; Geoffrey Liu; Steven Narod; Hans E Krokan; Frank Skorpen; Maiken Bratt Elvestad; Kristian Hveem; Lars Vatten; Jakob Linseisen; Françoise Clavel-Chapelon; Paolo Vineis; H Bas Bueno-de-Mesquita; Eiliv Lund; Carmen Martinez; Sheila Bingham; Torgny Rasmuson; Pierre Hainaut; Elio Riboli; Wolfgang Ahrens; Simone Benhamou; Pagona Lagiou; Dimitrios Trichopoulos; Ivana Holcátová; Franco Merletti; Kristina Kjaerheim; Antonio Agudo; Gary Macfarlane; Renato Talamini; Lorenzo Simonato; Ray Lowry; David I Conway; Ariana Znaor; Claire Healy; Diana Zelenika; Anne Boland; Marc Delepine; Mario Foglio; Doris Lechner; Fumihiko Matsuda; Helene Blanche; Ivo Gut; Simon Heath; Mark Lathrop; Paul Brennan Journal: Nature Date: 2008-04-03 Impact factor: 49.962
Authors: Thorgeir E Thorgeirsson; Frank Geller; Patrick Sulem; Thorunn Rafnar; Anna Wiste; Kristinn P Magnusson; Andrei Manolescu; Gudmar Thorleifsson; Hreinn Stefansson; Andres Ingason; Simon N Stacey; Jon T Bergthorsson; Steinunn Thorlacius; Julius Gudmundsson; Thorlakur Jonsson; Margret Jakobsdottir; Jona Saemundsdottir; Olof Olafsdottir; Larus J Gudmundsson; Gyda Bjornsdottir; Kristleifur Kristjansson; Halla Skuladottir; Helgi J Isaksson; Tomas Gudbjartsson; Gregory T Jones; Thomas Mueller; Anders Gottsäter; Andrea Flex; Katja K H Aben; Femmie de Vegt; Peter F A Mulders; Dolores Isla; Maria J Vidal; Laura Asin; Berta Saez; Laura Murillo; Thorsteinn Blondal; Halldor Kolbeinsson; Jon G Stefansson; Ingunn Hansdottir; Valgerdur Runarsdottir; Roberto Pola; Bengt Lindblad; Andre M van Rij; Benjamin Dieplinger; Meinhard Haltmayer; Jose I Mayordomo; Lambertus A Kiemeney; Stefan E Matthiasson; Hogni Oskarsson; Thorarinn Tyrfingsson; Daniel F Gudbjartsson; Jeffrey R Gulcher; Steinn Jonsson; Unnur Thorsteinsdottir; Augustine Kong; Kari Stefansson Journal: Nature Date: 2008-04-03 Impact factor: 49.962
Authors: Nubia Muñoz; F Xavier Bosch; Silvia de Sanjosé; Rolando Herrero; Xavier Castellsagué; Keerti V Shah; Peter J F Snijders; Chris J L M Meijer Journal: N Engl J Med Date: 2003-02-06 Impact factor: 91.245
Authors: S A Grando; R M Horton; E F Pereira; B M Diethelm-Okita; P M George; E X Albuquerque; B M Conti-Fine Journal: J Invest Dermatol Date: 1995-12 Impact factor: 8.551