Top

Published in:

Open Access 01-12-2017 | Research article

Clinical relevance of breast and gastric cancer-associated polymorphisms as potential susceptibility markers for oral clefts in the Brazilian population

Authors: Renato Assis Machado, Edimilson Martins de Freitas, Sibele Nascimento de Aquino, Daniella Reis B. Martelli, Mário Sérgio Oliveira Swerts, Silvia Regina de Almeida Reis, Darlene Camati Persuhn, Helenara Salvati Bertolossi Moreira, Verônica Oliveira Dias, Ricardo D. Coletta, Hercílio Martelli-Júnior

Published in: BMC Medical Genetics | Issue 1/2017

Abstract

Background

Epidemiological studies have indicated a higher incidence of breast and gastric cancer in patients with nonsyndromic cleft lip with or without cleft palate (NSCL ± P) and their relatives, which can be based on similar genetic triggers segregated within family with NSCL ± P.

Methods

This multicenter study evaluated the association of 9 single nucleotide polymorphisms (SNP) in AXIN2 and CDH1, representing genes consistently altered in breast and gastric tumors, with NSCL ± P in 223 trios (father, mother and patient with NSCL ± P) by transmission disequilibrium test (TDT).

Results

Our results showed that the minor A allele of rs7210356 (p = 0.01) and the T-G-G-A-G haplotype formed by rs7591, rs7210356, rs4791171, rs11079571 and rs3923087 SNPs (p = 0.03) in AXIN2 were significantly under-transmitted to patients with NSCL ± P. In CDH1 gene, the C-G-A-A and A-G-A-G haplotypes composed by rs16260, rs9929218, rs7186053 and rs4783573 polymorphisms were respectively over-transmitted (p = 0.01) and under-transmitted (p = 0.008) from parents to the children with NSCL ± P.

Conclusions

The results suggest that polymorphic variants in AXIN2 and CDH1 may be associated with NSCL ± P susceptibility, and reinforce the putative link between cancer and oral clefts.

Available only for authorised users

Dixon MJ, Marazita ML, Beaty TH, Murray JC. Cleft lip and palate: understanding genetic and environmental influences. Nat Rev Genet. 2011;12(3):167–78.CrossRefPubMedPubMedCentral

Marazita ML, Lidral AC, Murray JC, Field LL, Maher BS, Goldstein McHenry T, Cooper ME, Govil M, Daack-Hirsch S, Riley B, Jugessur A, Felix T, Morene L, Mansilla MA, Vieira AR, Doheny K, Pugh E, Valencia-Ramirez C, Arcos-Burgos M. Genome scan, fine-mapping, and candidate gene analysis of non-syndromic cleft lip with or without cleft palate reveals phenotype-specific differences in linkage and association results. Hum Hered. 2009;68(3):151–70.CrossRefPubMedPubMedCentral

Meng L, Bian Z, Torensma R, Von den Hoff JW. Biological mechanisms in palatogenesis and cleft palate. J Dent Res. 2009;88(1):22–33.CrossRefPubMed

Mangold E, Ludwig KU, Nothen MM. Breakthroughs in the genetics of orofacial clefting. Trends Mol Med. 2011;17(12):725–33.CrossRefPubMed

Harville EW, Wilcox AJ, Lie RT, Vindenes H, Abyholm F. Cleft lip and palate versus cleft lip only: are they distinct defects? Am J Epidemiol. 2005;162(5):448–53.CrossRefPubMed

Grosen D, Chevrier C, Skytthe A, Bille C, Molsted K, Sivertsen A, Murray JC, Christensen K. A cohort study of recurrence patterns among more than 54,000 relatives of oral cleft cases in Denmark: support for the multifactorial threshold model of inheritance. J Med Genet. 2010;47(3):162–8.CrossRefPubMed

Murthy J, Bhaskar L. Current concepts in genetics of nonsyndromic clefts. Indian J Plast Surg. 2009;42(1):68–81.CrossRefPubMedPubMedCentral

Machado RA, Moreira HS, de Aquino SN, Martelli-Junior H, de Almeida Reis SR, Persuhn DC, Wu T, Yuan Y, Coletta RD. Interactions between RAD51 rs1801321 and maternal cigarette smoking as risk factor for nonsyndromic cleft lip with or without cleft palate. Am J Med Genet A. 2016;170(2):536–9.CrossRef

Wu T, Schwender H, Ruczinski I, Murray JC, Marazita ML, Munger RG, Hetmanski JB, Parker MM, Wang P, Murray T, Taub M, Li S, Redett RJ, Fallin MD, Liang KY, Wu-Chou YH, Chong SS, Yeow V, Ye X, Wang H, Huang S, Jabs EW, Shi B, Wilcox AJ, Jee SH, Scott AF, Beaty TH. Evidence of gene-environment interaction for two genes on chromosome 4 and environmental tobacco smoke in controlling the risk of nonsyndromic cleft palate. PLoS One. 2014;9(2):e88088.CrossRefPubMedPubMedCentral

10.

James A, Oluwatosin B, Njideka G, Babafemi BOG, Olufemi D, Leo R, Folorunso I, Phylis OO. Cleft palate in hiv-exposed newborns of mothers on highly active antiretroviral therapy. Oral Surg. 2014;7 Suppl 1:102–6.PubMedPubMedCentral

11.

Figueiredo JC, Ly S, Magee KS, Ihenacho U, Baurley JW, Sanchez-Lara PA, Brindopke F, Nguyen TH, Nguyen V, Tangco MI, Giron M, Abrahams T, Jang G, Vu A, Zolfaghari E, Yao CA, Foong A, DeClerk YA, Samet JM, Magee W. Parental risk factors for oral clefts among Central Africans, Southeast Asians, and Central Americans. Birth Defects Res A Clin Mol Teratol. 2015;103(10):863–79.CrossRefPubMedPubMedCentral

12.

Yuan Q, Blanton SH, Hecht JT. Genetic causes of nonsyndromic cleft lip with or without cleft palate. Adv Otorhinolaryngol. 2011;70:107–13.PubMed

13.

Mehrotra D. Genomic expression in non syndromic cleft lip and palate patients: a review. J Oral Biol Craniofac Res. 2015;5(2):86–91.CrossRefPubMedPubMedCentral

14.

Taioli E, Ragin C, Robertson L, Linkov F, Thurman NE, Vieira AR. Cleft lip and palate in family members of cancer survivors. Cancer Invest. 2010;28(9):958–62.CrossRefPubMedPubMedCentral

15.

Jindal A, Vieira AR. Family history of cleft lip and palate in subjects diagnosed with leukemia. Am J Med Genet A. 2012;158A(3):678–9.CrossRefPubMed

16.

Zhu JL, Basso O, Hasle H, Winther JF, Olsen JH, Olsen J. Do parents of children with congenital malformations have a higher cancer risk? a nationwide study in Denmark. Br J Cancer. 2002;87(5):524–8.CrossRefPubMedPubMedCentral

17.

Vieira AR, Khaliq S, Lace B. Risk of cancer in relatives of children born with isolated cleft lip and palate. Am J Med Genet A. 2012;158A(6):1503–4.CrossRefPubMed

18.

Goncalves E, Martelli DR, Coletta RD, Vieira AR, Caldeira AP, Martelli Jr H. Risk of leukemia in first degree relatives of patients with nonsyndromic cleft lip and palate. Braz Oral Res. 2014;28(1):1–3.CrossRefPubMed

19.

Frebourg T, Oliveira C, Hochain P, Karam R, Manouvrier S, Graziadio C, Vekemans M, Hartmann A, Baert-Desurmont S, Alexandre C, Lejeune Dumoulin S, Marroni C, Martin C, Castedo S, Lovett M, Winston J, Machado JC, Attié T, Jabs EW, Cai J, Pellerin P, Triboulet JP, Scotte M, Le Pessot F, Hedouin A, Carneiro F, Blayau M, Seruca R. Cleft lip/palate and CDH1/E-cadherin mutations in families with hereditary diffuse gastric cancer. J Med Genet. 2006;43(2):138–42.CrossRefPubMedPubMedCentral

20.

Cavallaro U, Dejana E. Adhesion molecule signalling: not always a sticky business. Nat Rev Mol Cell Biol. 2011;12(3):189–97.CrossRefPubMed

21.

Li S, Wang C, Liu X, Hua S. The roles of AXIN2 in tumorigenesis and epigenetic regulation. Fam Cancer. 2015;14(2):325–31.CrossRefPubMed

22.

Mani P, Jarrell A, Myers J, Atit R. Visualizing canonical Wnt signaling during mouse craniofacial development. Dev Dyn. 2010;239(1):354–63.PubMedPubMedCentral

23.

Chiquet BT, Blanton SH, Burt A, Ma D, Stal S, Mulliken JB, Hecht JT. Variation in WNT genes is associated with non-syndromic cleft lip with or without cleft palate. Hum Mol Genet. 2008;17(14):2212–8.CrossRefPubMedPubMedCentral

24.

Lu YP, Han WT, Liu Q, Li JX, Li ZJ, Jiang M, Xu W. Variations in WNT3 gene are associated with incidence of non-syndromic cleft lip with or without cleft palate in a northeast Chinese population. Genet Mol Res. 2015;14(4):12646–53.CrossRefPubMed

25.

Galamb O, Kalmár A, Péterfia B, Csabai I, Bodor A, Ribli D, Krenács T, Patai ÁV, Wichmann B, Barták BK, Tóth K, Valcz G, Spisák S, Tulassay Z, Molnár B. Aberrant DNA methylation of WNT pathway genes in the development and progression of CIMP-negative colorectal cancer. Epigenetics. 2016;11(8):588–602.CrossRefPubMed

26.

Chan DW, Mak CS, Leung TH, Chan KK, Ngan HY. Down-regulation of Sox7 is associated with aberrant activation of Wnt/b-catenin signaling in endometrial cancer. Oncotarget. 2012;3(12):1546–56.CrossRefPubMedPubMedCentral

27.

Baarsma HA, Konigshoff M, Gosens R. The WNT signaling pathway from ligand secretion to gene transcription: molecular mechanisms and pharmacological targets. Pharmacol Ther. 2013;138(1):66–83.CrossRefPubMed

28.

Wang SH, Li N, Wei Y, Li QR, Yu ZP. beta-catenin deacetylation is essential for WNT-induced proliferation of breast cancer cells. Mol Med Rep. 2014;9(3):973–8.PubMed

29.

Wang X, Goode EL, Fredericksen ZS, Vierkant RA, Pankratz VS, Liu-Mares W, Rider DN, Vachon CM, Cerhan JR, Olson JE, Couch FJ. Association of genetic variation in genes implicated in the beta-catenin destruction complex with risk of breast cancer. Cancer Epidemiol Biomarkers Prev. 2008;17(8):2101–8.CrossRefPubMedPubMedCentral

30.

Paredes J, Figueiredo J, Albergaria A, Oliveira P, Carvalho J, Ribeiro AS, Caldeira J, Costa AM, Simões-Correia J, Oliveira MJ, Pinheiro H, Pinho SS, Mateus R, Reis CA, Leite M, Fernandes MS, Schmitt F, Carneiro F, Figueiredo C, Oliveira C, Seruca R. Epithelial E- and P-cadherins: role and clinical significance in cancer. Biochim Biophys Acta. 2012;1826(2):297–311.PubMed

31.

Liu X, Chu KM. E-cadherin and gastric cancer: cause, consequence, and applications. Biomed Res Int. 2014;2014:637308.PubMedPubMedCentral

32.

Jiang B, Zhu K, Shao H, Bao C, Ou J, Sun W. Lack of association between the CDH1 polymorphism and gastric cancer susceptibility: a meta-analysis. Sci Rep. 2015;5:7891.CrossRefPubMedPubMedCentral

33.

Li YL, Tian Z, Zhang JB, Fu BY. CDH1 promoter polymorphism and stomach cancer susceptibility. Mol Biol Rep. 2012;39(2):1283–6.CrossRefPubMed

34.

van der Post RS, Vogelaar IP, Carneiro F, Guilford P, Huntsman D, Hoogerbrugge N, Caldas C, Schreiber KE, Hardwick RH, Ausems MG, Bardram L, Benusiglio PR, Bisseling TM, Blair V, Bleiker E, Boussioutas A, Cats A, Coit D, DeGregorio L, Figueiredo J, Ford JM, Heijkoop E, Hermens R, Humar B, Kaurah P, Keller G, Lai J, Ligtenberg MJ, O’Donovan M, Oliveira C, Pinheiro H, Ragunath K, Rasenberg E, Richardson S, Roviello F, Schackert H, Seruca R, Taylor A, Ter Huurne A, Tischkowitz M, Joe ST, van Dijck B, van Grieken NC, van Hillegersberg R, van Sandick JW, Vehof R, van Krieken JH, Fitzgerald RC. Hereditary diffuse gastric cancer: updated clinical guidelines with an emphasis on germline CDH1 mutation carriers. J Med Genet. 2015;52(6):361–74.CrossRefPubMedPubMedCentral

35.

Han Y, Zhou L, Ma L, Li D, Xu M, Yuan H, Ma J, Zhang W, Jiang H, Wu Y, Wang L, Pan Y. The axis inhibition protein 2 polymorphisms and non-syndromic orofacial clefts susceptibility in a Chinese Han population. J Oral Pathol Med. 2014;43(7):554–60.CrossRefPubMed

36.

Letra A, Bjork B, Cooper ME, Szabo-Rogers H, Deleyiannis FW, Field LL, Czeizel AE, Ma L, Garlet GP, Poletta FA, Mereb JC, Lopez-Camelo JS, Castilla EE, Orioli IM, Wendell S, Blanton SH, Liu K, Hecht JT, Marazita ML, Vieira AR, Silva RM. Association of AXIN2 with non-syndromic oral clefts in multiple populations. J Dent Res. 2012;91(5):473–8.CrossRefPubMedPubMedCentral

37.

Letra A, Menezes R, Granjeiro JM, Vieira AR. AXIN2 and CDH1 polymorphisms, tooth agenesis, and oral clefts. Birth Defects Res A Clin Mol Teratol. 2009;85(2):169–73.CrossRefPubMedPubMedCentral

38.

Bureau A, Parker MM, Ruczinski I, Taub MA, Marazita ML, Murray JC, Mangold E, Noethen MM, Ludwig KU, Hetmanski JB, Bailey-Wilson JE, Cropp CD, Li Q, Szymczak S, Albacha-Hejazi H, Alqosayer K, Field LL, Wu-Chou YH, Doheny KF, Ling H, Scott AF, Beaty TH. Whole exome sequencing of distant relatives in multiplex families implicates rare variants in candidate genes for oral clefts. Genetics. 2014;197(3):1039–44.CrossRefPubMedPubMedCentral

39.

Song Y, Zhang S. Association of CDH1 promoter polymorphism and the risk of non-syndromic orofacial clefts in a Chinese Han population. Arch Oral Biol. 2011;56(1):68–72.CrossRefPubMed

40.

Hozyasz KK, Mostowska A, Wojcicki P, Lasota A, Offert B, Balcerek A, Dunin-Wilczyńska I, Jagodziński PP. Nucleotide variants of the cancer predisposing gene CDH1 and the risk of non-syndromic cleft lip with or without cleft palate. Fam Cancer. 2014;13(3):415–21.CrossRefPubMedPubMedCentral

41.

Spina V, Psillakis JM, Lapa FS, Ferreira MC. Classification of cleft lip and cleft palate. Suggested changes. Rev Hosp Clin Fac Med Sao Paulo. 1972;27(1):5–6.PubMed

42.

Aidar M, Line SR. A simple and cost-effective protocol for DNA isolation from buccal epithelial cells. Braz Dent J. 2007;18(2):148–52.CrossRefPubMed

43.

Alanazi MS, Parine NR, Shaik JP, Alabdulkarim HA, Ajaj SA, Khan Z. Association of single nucleotide polymorphisms in Wnt signaling pathway genes with breast cancer in Saudi patients. PLoS One. 2013;8(3):e59555.CrossRefPubMedPubMedCentral

44.

Jing H, Dai F, Zhao C, Yang J, Li L, Kota P, Mao L, Xiang K, Zheng C, Yang J. Association of genetic variants in and promoter hypermethylation of CDH1 with gastric cancer: a meta-analysis. Medicine (Baltimore). 2014;93(19):e107.CrossRef

45.

Zhan Z, Wu J, Zhang JF, Yang YP, Tong S, Zhang CB, Li J, Yang XW, Dong W. CDH1 gene polymorphisms, plasma CDH1 levels and risk of gastric cancer in a Chinese population. Mol Biol Rep. 2012;39(8):8107–13.CrossRefPubMed

46.

Mostowska A, Hozyasz KK, Wojcicki P, Lasota A, Dunin-Wilczynska I, Jagodzinski PP. Association of DVL2 and AXIN2 gene polymorphisms with cleft lip with or without cleft palate in a Polish population. Birth Defects Res A Clin Mol Teratol. 2012;94(11):943–50.CrossRefPubMed

47.

Menezes R, Marazita ML, Goldstein McHenry T, Cooper ME, Bardi K, Brandon C, Letra A, Martin RA, Vieira AR. AXIS inhibition protein 2, orofacial clefts and a family history of cancer. J Am Dent Assoc. 2009;140(1):80–4.CrossRefPubMedPubMedCentral

48.

Al-Moundhri MS, Al-Khanbashi M, Al-Kindi M, Al-Nabhani M, Burney IA, Al-Farsi A, Al-Bahrani B. Association of E-cadherin (CDH1) gene polymorphisms and gastric cancer risk. World J Gastroenterol. 2010;16(27):3432–6.CrossRefPubMedPubMedCentral

49.

Kerrigan JJ, Mansell JP, Sengupta A, Brown N, Sandy JR. Palatogenesis and potential mechanisms for clefting. J R Coll Surg Edinb. 2000;45(6):351–8.PubMed

Title: Clinical relevance of breast and gastric cancer-associated polymorphisms as potential susceptibility markers for oral clefts in the Brazilian population
Authors: Renato Assis Machado
Edimilson Martins de Freitas
Sibele Nascimento de Aquino
Daniella Reis B. Martelli
Mário Sérgio Oliveira Swerts
Silvia Regina de Almeida Reis
Darlene Camati Persuhn
Helenara Salvati Bertolossi Moreira
Verônica Oliveira Dias
Ricardo D. Coletta
Hercílio Martelli-Júnior
Publication date: 01-12-2017
Publisher: BioMed Central
Published in: BMC Medical Genetics / Issue 1/2017
Electronic ISSN: 1471-2350
DOI: https://doi.org/10.1186/s12881-017-0390-y

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Clinical relevance of breast and gastric cancer-associated polymorphisms as potential susceptibility markers for oral clefts in the Brazilian population

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2017

Association of NOS3 gene polymorphisms with essential hypertension in Sudanese patients: a case control study

SCN8A mutations in Chinese patients with early onset epileptic encephalopathy and benign infantile seizures

Vitamin D receptor gene polymorphisms in association with diabetic nephropathy: a systematic review and meta-analysis

African ancestry is associated with facial melasma in women: a cross-sectional study

Breast cancer protection by genomic imprinting in close kin families

Characterization of a novel disease-causing mutation in exon 1 of SH2D1A gene through amplicon sequencing: a case report on HLH