Skip to main content
SpringerLink
Log in

Impact of Phospholipase A2 Group IIa Gene Polymorphism on Phenotypic Features of Patients with Familial Adenomatous Polyposis

  • Published:
Diseases of the Colon & Rectum

Purpose

Phospholipase A2 Group IIa has been suggested to be a possible disease modifier gene in familial adenomatous polyposis. This investigation was designed to elucidate possible association between phospholipase A2 Group IIa polymorphism and phenotypes of patients with familial adenomatous polyposis.

Methods

Phospholipase A2 Group IIa was examined by polymerase chain reaction-based single strand conformation polymorphism and direct sequencing in 55 patients from 45 families with familial adenomatous polyposis. The patients were examined by gastroduodenoscopy plus biopsy with respect to fundic gland polyposis and gastroduodenal adenomas. Helicobacter pylori status was determined by rapid urease test. Contributions of genetic alteration and Helicobacter pylori infection to intestinal and extraintestinal lesions were investigated.

Results

Four types of single nucleotide polymorphism were found in exon 3 of phospholipase A2 Group IIa, among which single nucleotide polymorphism in codon 32 was the most frequent. The prevalence of fundic gland polyposis was higher in patients positive for single nucleotide polymorphism of phospholipase A2 Group IIa than those negative for single nucleotide polymorphism (61 vs. 33 percent; P < 0.05). In contrast, positive rate of Helicobacter pylori infection was lower in the former than in the latter (22 vs. 52 percent; P < 0.05). The prevalence of the other phenotypes was not different significantly. Logistic regression analysis revealed a possibility toward single nucleotide polymorphism of phospholipase A2 Group IIa as an independent risk factor for fundic gland polyposis (95 percent confidence interval, 00.9–14.3; P = 0.06).

Conclusions

Phospholipase A2 Group IIa may be a modifier gene for fundic gland polyposis in patients with familial adenomatous polyposis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. I Nishisho Y Nakamura Y Miyoshi et al. (1991) ArticleTitleMutation of a chromosome 5q21 genes in FAP and colorectal cancer patient Science 253 665–669 Occurrence Handle1651563 Occurrence Handle10.1126/science.1651563 Occurrence Handle1:CAS:528:DyaK3MXmt1Gitr0%3D

    Article  PubMed  CAS  Google Scholar 

  2. L Sporio B Otterud D Stauffer et al. (1992) ArticleTitleLinkage of a variant or attenuated form of adenomatous polyposis coli to the adenomatous polyposis coli (APC) locus Am J Hum Genet 51 92–100

    Google Scholar 

  3. M Leppert R Burt JP Hughes et al. (1990) ArticleTitleGenetic analysis of an inherited predisposition to colon cancer in a family with a variable number of adenomatous polyps N Engl J Med 322 904–908 Occurrence Handle2156161 Occurrence Handle1:STN:280:DyaK3c7ptVOksg%3D%3D Occurrence Handle10.1056/NEJM199003293221306

    Article  PubMed  CAS  Google Scholar 

  4. P Paul T Letteboer L Gelbert J Groden R White MJ Coppes (1993) ArticleTitleIdentical APC exon 15 mutations result in a variable phenotype in familial adenomatous polyposis Hum Mol Genet 2 925–931 Occurrence Handle8395941 Occurrence Handle10.1093/hmg/2.7.925 Occurrence Handle1:CAS:528:DyaK3sXms1Olu74%3D

    Article  PubMed  CAS  Google Scholar 

  5. FM Giardiello AJ Krush GM Petersen et al. (1994) ArticleTitlePhenotypic variability of familial adenomatous polyposis in 11 unrelated families with identical APC gene mutation Gastroenterology 106 1542–1547 Occurrence Handle8194700 Occurrence Handle1:STN:280:DyaK2c3lt1Gjuw%3D%3D

    PubMed  CAS  Google Scholar 

  6. AR Moser WF Dove KA Roth JI Gordon (1992) ArticleTitleThe MIN (multiple intestinal neoplasia) mutation. Its effect on gut epithelium cell differentiation and interaction with a modifier system J Cell Biol 116 517–526

    Google Scholar 

  7. M MacPhee KP Chepenik RA Liddell KK Nelson LD Siracusa AM Buchberg (1995) ArticleTitleThe secretory phospholipase A2 gene is a candidate for the Mom1 locus, a major modifier of APC Min-induced intestinal neoplasia Cell 81 957–966 Occurrence Handle7781071 Occurrence Handle10.1016/0092-8674(95)90015-2 Occurrence Handle1:CAS:528:DyaK2MXmsVagt7o%3D

    Article  PubMed  CAS  Google Scholar 

  8. KA Silverman R Koratkar LD Siracusa AM Buchberg (2002) ArticleTitleIdentification of the modifier of Min 2 (Mom2) locus, a new mutation that influences APC-induced neoplasia Genome Res 12 88–97 Occurrence Handle11779834 Occurrence Handle10.1101/gr.206002 Occurrence Handle1:CAS:528:DC%2BD38XksV2qsg%3D%3D

    Article  PubMed  CAS  Google Scholar 

  9. K Takaku M Sonoshita N Sasaki et al. (2000) ArticleTitleSuppression of intestinal polyposis in APCD716 knockout mice by an additional mutation in the cytosolic phospholipase A2 gene J Biol Chem 275 34013–34016 Occurrence Handle10969066 Occurrence Handle10.1074/jbc.M003696200 Occurrence Handle1:CAS:528:DC%2BD3cXotFWmtbk%3D

    Article  PubMed  CAS  Google Scholar 

  10. RT Cormier A Bilger AJ Lillich et al. (2000) ArticleTitleThe Mom1AKR intestinal tumor resistance region consists of PLA2g2a and a locus distal to D4Min64 Oncogene 19 3182–3192 Occurrence Handle10918573 Occurrence Handle10.1038/sj.onc.1203646 Occurrence Handle1:CAS:528:DC%2BD3cXlt1Wisrk%3D

    Article  PubMed  CAS  Google Scholar 

  11. BP Kennedy C Soravia J Moffat et al. (1998) ArticleTitleOverexpression of the nonpancreatic secretory group II PLA2 messenger RNA and protein in colorectal adenomas from familial adenomatous polyposis Cancer Res 58 500–503 Occurrence Handle9458096 Occurrence Handle1:STN:280:DyaK1c7hslejsg%3D%3D

    PubMed  CAS  Google Scholar 

  12. T Matsumoto M Iida Y Kobori et al. (2002) ArticleTitleGenetic predisposition to clinical manifestations in familial adenomatous polyposis with special reference to duodenal lesions Am J Gastroenterol 97 180–185 Occurrence Handle11808944 Occurrence Handle10.1111/j.1572-0241.2002.05434.x

    Article  PubMed  Google Scholar 

  13. S Nakamura T Matsumoto Y Kobori M Iida (2002) ArticleTitleImpact of Helicobacter pylori infection and mucosal atrophy on gastric lesions in patients with familial adenomatous polyposis Gut 52 485–489 Occurrence Handle10.1136/gut.51.4.485

    Article  Google Scholar 

  14. T Sasaki T Tahira A Suzuki et al. (2001) ArticleTitlePrecise estimation of allele frequencies of single-nucleotide polymorphisms by a quantitative SSCP analysis of pooled DNA Am J Hum Genet 68 214–218 Occurrence Handle11083945 Occurrence Handle10.1086/316928 Occurrence Handle1:CAS:528:DC%2BD3MXnt1egtQ%3D%3D

    Article  PubMed  CAS  Google Scholar 

  15. K Heinimann B Mullhaupt W Weber et al. (1998) ArticleTitlePhenotypic differences in familial adenomatous polyposis based on APC gene mutation status Gut 43 675–679 Occurrence Handle9824350 Occurrence Handle1:STN:280:DyaK1M%2FntFamtA%3D%3D Occurrence Handle10.1136/gut.43.5.675

    Article  PubMed  CAS  Google Scholar 

  16. FM Giardiello GM Petersen S Piantadosi et al. (1997) ArticleTitleAPC gene mutations and extraintestinal phenotype of familial adenomatous polyposis Gut 40 521–525 Occurrence Handle9176082 Occurrence Handle1:CAS:528:DyaK2sXjsFOksbg%3D

    PubMed  CAS  Google Scholar 

  17. YL Wallis DG Morton CM McKeown F Macdonald (1999) ArticleTitleMolecular analysis of the APC gene in 205 families. Extended genotype-phenotype correlations in FAP and evidence for the role of APC amino acid changes in colorectal cancer predisposition J Med Genet 36 14–20 Occurrence Handle9950360 Occurrence Handle1:CAS:528:DyaK1MXitVKrtrc%3D

    PubMed  CAS  Google Scholar 

  18. H Nagase Y Miyoshi A Horii et al. (1992) ArticleTitleCorrelation between the location of germ-line mutations in the APC gene and the number of colorectal polyps in familial adenomatous polyposis patients Cancer Res 52 4055–4057 Occurrence Handle1319838 Occurrence Handle1:CAS:528:DyaK38XkvVOktLs%3D

    PubMed  CAS  Google Scholar 

  19. S Olschwang A Tiret P Laurent-Puig M Muleris R Parc G Thomas (1993) ArticleTitleRestriction of ocular fundus lesions to a specific subgroup of APC mutations in adenomatous polyposis coli patients Cell 75 959–968 Occurrence Handle8252631 Occurrence Handle10.1016/0092-8674(93)90539-3 Occurrence Handle1:CAS:528:DyaK2cXltFyjsg%3D%3D

    Article  PubMed  CAS  Google Scholar 

  20. YL Wallis F Macdonald M Hulten et al. (1994) ArticleTitleGenotype-phenotype correlation between position of constitutional APC gene mutation and CHRPE expression in familial adenomatous polyposis Hum Genet 94 543–548 Occurrence Handle7959691 Occurrence Handle10.1007/BF00211023 Occurrence Handle1:CAS:528:DyaK2MXivFWntr8%3D

    Article  PubMed  CAS  Google Scholar 

  21. R Caspari S Olschwang W Friedl et al. (1995) ArticleTitleFamilial adenomatous polyposis. Desmoid tumors and lack of ophthalmic lesions (CHRPE) associated with APC mutations beyond codon 1444 Hum Mol Genet 4 337–340 Occurrence Handle7795585 Occurrence Handle10.1093/hmg/4.3.337 Occurrence Handle1:CAS:528:DyaK2MXkvVeju7w%3D

    Article  PubMed  CAS  Google Scholar 

  22. DR Davies JG Armstrong N Thakker et al. (1995) ArticleTitleSevere Gardner syndrome in families with mutations restricted to a specific region of the APC gene Am J Hum Genet 57 1151–1158 Occurrence Handle7485167 Occurrence Handle1:STN:280:DyaK28%2Fis1Wisw%3D%3D

    PubMed  CAS  Google Scholar 

  23. Z Dobbie M Spycher JL Mary et al. (1996) ArticleTitleCorrelation between the development of extracolonic manifestations in FAP patients and mutations beyond codon 1403 in the APC gene J Med Genet 33 274–280 Occurrence Handle8730280 Occurrence Handle1:CAS:528:DyaK28XivFWktr4%3D

    PubMed  CAS  Google Scholar 

  24. K Heinimann A Thompson A Locher et al. (2001) ArticleTitleNontruncating APC germ-line mutations and mismatch repair deficiency play a minor role in APC mutation-negative polyposis Cancer Res 61 7616–7622 Occurrence Handle11606402 Occurrence Handle1:CAS:528:DC%2BD3MXnvFShtrs%3D

    PubMed  CAS  Google Scholar 

  25. I Nimmrich W Friedl R Kruse et al. (1997) ArticleTitleLoss of the PLA2G2A gene in a sporadic colorectal tumor of a patient with a PLA2G2A germline mutation and absence of PLA2G2A germline alterations in patients with FAP Hum Genet 100 345–349 Occurrence Handle9272153 Occurrence Handle10.1007/s004390050514 Occurrence Handle1:CAS:528:DyaK2sXkvF2msr4%3D

    Article  PubMed  CAS  Google Scholar 

  26. LN Spirio W Kutchera MV Winstead et al. (1996) ArticleTitleThree secretary phospholipase A(2) genes that map to human chromosome 1P35–36 are not mutated in individuals with attenuated adenomatous polyposis coli Cancer Res 56 955–958 Occurrence Handle8640784 Occurrence Handle1:CAS:528:DyaK28XhtlKksL8%3D

    PubMed  CAS  Google Scholar 

  27. Z Dobbie H Muller RJ Scott (1996) ArticleTitleSecretory phospholipase A2 does not appear to be associated with phenotypic variation in familial adenomatous polyposis Hum Genet 98 386–390 Occurrence Handle8707313 Occurrence Handle10.1007/s004390050226 Occurrence Handle1:CAS:528:DyaK28Xls1Cgs7o%3D

    Article  PubMed  CAS  Google Scholar 

  28. Z Dobbie K Heinimann DT Bishop H Muller RJ Scott (1997) ArticleTitleIdentification of a modifier gene locus on chromosome 1p35–36 in familial adenomatous polyposis Hum Genet 99 653–657 Occurrence Handle9150735 Occurrence Handle10.1007/s004390050423 Occurrence Handle1:CAS:528:DyaK2sXjtl2qsr0%3D

    Article  PubMed  CAS  Google Scholar 

  29. IP Tomlinson NE Beck K Neale WF Bodmer (1996) ArticleTitleVariants at the secretary phospholipase A2 (PLA2g2a) locus. Analysis of associations with familial adenomatous polyposis and sporadic colorectal tumors Ann Hum Genet 60 369–376 Occurrence Handle8912789 Occurrence Handle1:STN:280:DyaK2s%2FmvFyjuw%3D%3D

    PubMed  CAS  Google Scholar 

  30. RT Cormier KH Hong RB Halberg et al. (1997) ArticleTitleSecretory phospholipase PLA2g2a confers resistance to intestinal tumorigenesis Nat Genet 17 88–91 Occurrence Handle9288104 Occurrence Handle10.1038/ng0997-88 Occurrence Handle1:CAS:528:DyaK2sXlvVGhtbs%3D

    Article  PubMed  CAS  Google Scholar 

  31. C Praml LC Amler S Dihlmann LH Finke P Schlag M Schwab (1998) ArticleTitleSecretory type II phospholipase A2 (PLA2g2a) expression status in colorectal carcinoma derived cell line and in normal colonic mucosa Oncogene 17 2009–2012 Occurrence Handle9788445 Occurrence Handle10.1038/sj.onc.1202121 Occurrence Handle1:CAS:528:DyaK1cXnt1Glt7o%3D

    Article  PubMed  CAS  Google Scholar 

  32. IP Tomlinson K Neale IC Talbot et al. (1996) ArticleTitleA modifying locus for familial adenomatous polyposis may be present on chromosome 1p35–p36 J Med Genet 36 268–273 Occurrence Handle10.1136/jmg.33.4.268

    Article  Google Scholar 

  33. T Tsuchigame R Saito Y Ogata et al. (1995) ArticleTitleClinical evaluation of gastric fundic gland polyps without familial polyposis coli Abdom Imaging 20 101–105 Occurrence Handle7787708 Occurrence Handle10.1007/BF00201512 Occurrence Handle1:STN:280:DyaK2MzgslCjsA%3D%3D

    Article  PubMed  CAS  Google Scholar 

  34. AG Shand AC Taylor M Banerjee et al. (2002) ArticleTitleGastric fundic gland polyps in southeast Scotland. Absence of adenomatous polyposis coli gene mutations and a strikingly low prevalence of Helicobacter pylori infection J Gastroenterol Hepatol 17 1161–1164 Occurrence Handle12453274 Occurrence Handle10.1046/j.1440-1746.2002.02863.x Occurrence Handle1:CAS:528:DC%2BD38XptVOnu7g%3D

    Article  PubMed  CAS  Google Scholar 

  35. N Watanabe H Seno T Nakajima et al. (2002) ArticleTitleRegression of fundic gland polyps following acquisition of Helicobacter pylori Gut 51 742–745 Occurrence Handle12377817 Occurrence Handle10.1136/gut.51.5.742 Occurrence Handle1:STN:280:DC%2BD38nitVGltA%3D%3D

    Article  PubMed  CAS  Google Scholar 

  36. TC Wang JR Goldenring C Dangler et al. (1998) ArticleTitleMice lacking secretory phospholipase A2 show altered apoptosis and differentiation with Helicobacter felis infection Gastroenterology 114 675–689 Occurrence Handle9516388 Occurrence Handle10.1016/S0016-5085(98)70581-5 Occurrence Handle1:CAS:528:DyaK1cXisVWms78%3D

    Article  PubMed  CAS  Google Scholar 

  37. HT Huhtinen JM Gronroos J Uksila DS Grass TJ Nevalainen VJ Laine (2004) ArticleTitleExperimental Helicobacter felis infection in transgenic mice expressing human group IIA phospholipase A2 Helicobacter 9 408–416 Occurrence Handle15361079 Occurrence Handle10.1111/j.1083-4389.2004.00257.x Occurrence Handle1:CAS:528:DC%2BD2cXovFOgu7g%3D

    Article  PubMed  CAS  Google Scholar 

  38. A Zwick M Munir CK Ryan et al. (1997) ArticleTitleGastric adenocarcinoma and dysplasia in fundic gland polyps of a patient with attenuated adenomatous polyposis coli Gastroenterology 113 659–663 Occurrence Handle9247488 Occurrence Handle10.1053/gast.1997.v113.pm9247488 Occurrence Handle1:STN:280:DyaK2szptVKgsw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  39. TT Wu S Kornacki A Rashid JH Yardley SR Hamilton (1998) ArticleTitleDysplasia and dysregulation of proliferation in foveolar and surface epithelia of fundic gland polyps from patients with familial adenomatous polyposis Am J Surg Pathol 22 293–298 Occurrence Handle9500770 Occurrence Handle10.1097/00000478-199803000-00003 Occurrence Handle1:STN:280:DyaK1c7mtVCjtQ%3D%3D

    Article  PubMed  CAS  Google Scholar 

  40. WT Hofgartner M Thorp MW Ramus et al. (1999) ArticleTitleGastric adenocarcinoma associated with fundic gland polyposis with attenuated familial adenomatous polyposis Am J Gastroenterol 94 2275–2281 Occurrence Handle10445562 Occurrence Handle1:STN:280:DyaK1Mznt1Ogtg%3D%3D

    PubMed  CAS  Google Scholar 

  41. S Sekine T Shimoda S Nimura et al. (2004) ArticleTitleHigh-grade dysplasia associated with fundic gland polyposis in a familial adenomatous polyposis patient, with special reference to APC mutationprofiles Mod Pathol 17 421–426 Occurrence Handle10.1038/modpathol.3800178 Occurrence Handle1:CAS:528:DC%2BD2cXhtVWltLrN

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank Dr. Koji Yonemoto and Dr. Koichi Asano for assistance.

Author information

Authors and Affiliations

  1. Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka, 812-8582, Japan

    Ritsuko Yanaru-Fujisawa M.D., Takayuki Matsumoto M.D., Shotaro Nakamura M.D. & Mitsuo Iida M.D.

  2. Division of Genome Analysis, Department of Genetic Information, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan

    Yoji Kukita Ph.D. & Kenshi Hayashi Ph.D.

  3. Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Takashi Yao M.D.

Authors
  1. Ritsuko Yanaru-Fujisawa M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Takayuki Matsumoto M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yoji Kukita Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shotaro Nakamura M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Takashi Yao M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kenshi Hayashi Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mitsuo Iida M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ritsuko Yanaru-Fujisawa M.D..

About this article

Cite this article

Yanaru-Fujisawa, R., Matsumoto, T., Kukita, Y. et al. Impact of Phospholipase A2 Group IIa Gene Polymorphism on Phenotypic Features of Patients with Familial Adenomatous Polyposis. Dis Colon Rectum 50, 223–231 (2007). https://doi.org/10.1007/s10350-006-0780-2

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10350-006-0780-2

Key words

Search

Navigation