Skip to main content
Top
Published in: BMC Cancer 1/2009

Open Access 01-12-2009 | Research article

The Int7G24A variant of transforming growth factor-beta receptor type I is a risk factor for colorectal cancer in the male Spanish population: a case-control study

Authors: Adela Castillejo, Trinidad Mata-Balaguer, Carla Guarinos, María-Isabel Castillejo, Ana Martínez-Cantó, Víctor-Manuel Barberá, Paola Montenegro, Enrique Ochoa, Rafael Lázaro, Carmen Guillén-Ponce, Alfredo Carrato, José-Luís Soto

Published in: BMC Cancer | Issue 1/2009

Login to get access

Abstract

Background

The Int7G24A variant of transforming growth factor-beta receptor type I (TGFBR1) has been shown to increase the risk for kidney, ovarian, bladder, lung and breast cancers. Its role in colorectal cancer (CRC) has not been established. The aims of this study were to assess the association of TGFBR1*Int7G24A variant with CRC occurrence, patient age, gender, tumour location and stage.

Methods

We performed a case-control study with 504 cases of sporadic CRC; and 504 non-cancerous age, gender and ethnically matched controls. Genotyping analysis was performed using allelic discrimination assay by real time PCR.

Results

The Int7G24A variant was associated with increased CRC incidence in an additive model of inheritance (P for trend = 0.005). No significant differences were found between Int7G24A genotypes and tumour location or stage. Interestingly, the association of the Int7G24A variant with CRC risk was significant in men (odds ratio 4.10 with 95% confidence intervals 1.41-11.85 for homozygous individuals; P for trend = 0.00023), but not in women. We also observed an increase in susceptibility to CRC for individuals aged less than 70 years.

Conclusion

Our data suggest that the Int7G24A variant represents a risk factor for CRC in the male Spanish population.
Appendix
Available only for authorised users
Literature
1.
go back to reference Siegel PM, Massagué J: Cytostatic and apoptotic actions of TGF-beta in homeostasis and cancer. Nat Rev Cancer. 2003, 3 (11): 807-821. 10.1038/nrc1208.CrossRefPubMed Siegel PM, Massagué J: Cytostatic and apoptotic actions of TGF-beta in homeostasis and cancer. Nat Rev Cancer. 2003, 3 (11): 807-821. 10.1038/nrc1208.CrossRefPubMed
2.
go back to reference Bian Y, Kaklamani V, Reich J, Pasche B: TGF-beta signaling alterations in cancer. Cancer Treat Res. 2003, 115: 73-94. full_text.CrossRefPubMed Bian Y, Kaklamani V, Reich J, Pasche B: TGF-beta signaling alterations in cancer. Cancer Treat Res. 2003, 115: 73-94. full_text.CrossRefPubMed
3.
go back to reference Massagué J, Blain SW, Lo RS: TGFbeta signaling in growth control, cancer, and heritable disorders. Cell. 2000, 103 (2): 295-309. 10.1016/S0092-8674(00)00121-5.CrossRefPubMed Massagué J, Blain SW, Lo RS: TGFbeta signaling in growth control, cancer, and heritable disorders. Cell. 2000, 103 (2): 295-309. 10.1016/S0092-8674(00)00121-5.CrossRefPubMed
4.
go back to reference Pasche B, Kaklamani V, Hou N, Young T, Rademaker A, Peterlongo P, Ellis N, Offit K, Caldes T, Reiss M, Zheng T: TGFBR1*6A and cancer: a meta-analysis of 12 case-control studies. J Clin Oncol. 2004, 22 (4): 756-758. 10.1200/JCO.2004.99.271.CrossRefPubMed Pasche B, Kaklamani V, Hou N, Young T, Rademaker A, Peterlongo P, Ellis N, Offit K, Caldes T, Reiss M, Zheng T: TGFBR1*6A and cancer: a meta-analysis of 12 case-control studies. J Clin Oncol. 2004, 22 (4): 756-758. 10.1200/JCO.2004.99.271.CrossRefPubMed
5.
go back to reference Skoglund J, Song B, Dalén J, Dedorson S, Edler D, Hjern F, Holm J, Lenander C, Lindforss U, Lundqvist N, Olivecrona H, Olsson L, Påhlman L, Rutegård J, Smedh K, Törnqvist A, Houlston RS, Lindblom A: Lack of an association between the TGFBR1*6A variant and colorectal cancer risk. Clin Cancer Res. 2007, 13 (12): 3748-3752. 10.1158/1078-0432.CCR-06-2865.CrossRefPubMed Skoglund J, Song B, Dalén J, Dedorson S, Edler D, Hjern F, Holm J, Lenander C, Lindforss U, Lundqvist N, Olivecrona H, Olsson L, Påhlman L, Rutegård J, Smedh K, Törnqvist A, Houlston RS, Lindblom A: Lack of an association between the TGFBR1*6A variant and colorectal cancer risk. Clin Cancer Res. 2007, 13 (12): 3748-3752. 10.1158/1078-0432.CCR-06-2865.CrossRefPubMed
6.
go back to reference Castillejo A, Mata-Balaguer T, Montenegro P, Ochoa E, Lázaro R, Martínez-Cantó A, Castillejo MI, Guarinos C, Barberá VM, Guillén-Ponce C, Carrato A, Soto JL: The TGFBR1*6Aallele is not associated with susceptibility to colorectal cancer in a Spanish population: a case-control study. BMC Cancer. Castillejo A, Mata-Balaguer T, Montenegro P, Ochoa E, Lázaro R, Martínez-Cantó A, Castillejo MI, Guarinos C, Barberá VM, Guillén-Ponce C, Carrato A, Soto JL: The TGFBR1*6Aallele is not associated with susceptibility to colorectal cancer in a Spanish population: a case-control study. BMC Cancer.
7.
go back to reference Zhang HT, Fei QY, Chen F, Qi QY, Zou W, Wang JC, Zhang RM, Tao SH, Chen XF, Luo ZW: Mutational analysis of the transforming growth factor beta receptor type I gene in primary non-small cell lung cancer. Lung Cancer. 2003, 40 (3): 281-287.CrossRefPubMed Zhang HT, Fei QY, Chen F, Qi QY, Zou W, Wang JC, Zhang RM, Tao SH, Chen XF, Luo ZW: Mutational analysis of the transforming growth factor beta receptor type I gene in primary non-small cell lung cancer. Lung Cancer. 2003, 40 (3): 281-287.CrossRefPubMed
8.
go back to reference Zhang HT: Int7G24A variant of the TGFBR1 gene and cancer risk: a meta-analysis of three case-control studies. Lung Cancer. 2005, 49 (3): 419-420. 10.1016/j.lungcan.2005.03.038.CrossRefPubMed Zhang HT: Int7G24A variant of the TGFBR1 gene and cancer risk: a meta-analysis of three case-control studies. Lung Cancer. 2005, 49 (3): 419-420. 10.1016/j.lungcan.2005.03.038.CrossRefPubMed
9.
go back to reference Chen T, Jackson C, Costello B, Singer N, Colligan B, Douglass L, Pemberton J, Deddens J, Graff JR, Carter JH: An intronic variant of the TGFBR1 gene is associated with carcinomas of the kidney and bladder. Int J Cancer. 2004, 112 (3): 420-425. 10.1002/ijc.20419.CrossRefPubMed Chen T, Jackson C, Costello B, Singer N, Colligan B, Douglass L, Pemberton J, Deddens J, Graff JR, Carter JH: An intronic variant of the TGFBR1 gene is associated with carcinomas of the kidney and bladder. Int J Cancer. 2004, 112 (3): 420-425. 10.1002/ijc.20419.CrossRefPubMed
10.
go back to reference Chen T, Jackson CR, Link A, Markey MP, Colligan BM, Douglass LE, Pemberton JO, Deddens JA, Graff JR, Carter JH: Int7G24A variant of transforming growth factor-beta receptor type I is associated with invasive breast cancer. Clin Cancer Res. 2006, 12 (2): 392-397. 10.1158/1078-0432.CCR-05-1518.CrossRefPubMed Chen T, Jackson CR, Link A, Markey MP, Colligan BM, Douglass LE, Pemberton JO, Deddens JA, Graff JR, Carter JH: Int7G24A variant of transforming growth factor-beta receptor type I is associated with invasive breast cancer. Clin Cancer Res. 2006, 12 (2): 392-397. 10.1158/1078-0432.CCR-05-1518.CrossRefPubMed
11.
go back to reference Skoglund Lundin J, Vandrovcova J, Song B, Zhou X, Zelada-Hedman M, Werelius B, Houlston RS, Lindblom A: TGFBR1 variants TGFBR1(*)6A and Int7G24A are not associated with an increased familial colorectal cancer risk. Br J Cancer. 2009, 100 (10): 1674-1679. 10.1038/sj.bjc.6605054.CrossRefPubMedPubMedCentral Skoglund Lundin J, Vandrovcova J, Song B, Zhou X, Zelada-Hedman M, Werelius B, Houlston RS, Lindblom A: TGFBR1 variants TGFBR1(*)6A and Int7G24A are not associated with an increased familial colorectal cancer risk. Br J Cancer. 2009, 100 (10): 1674-1679. 10.1038/sj.bjc.6605054.CrossRefPubMedPubMedCentral
12.
go back to reference Loktionov A: Common gene polymorphisms, cancer progression and prognosis. Cancer Lett. 2004, 208 (1): 1-33. 10.1016/j.canlet.2004.02.009.CrossRefPubMed Loktionov A: Common gene polymorphisms, cancer progression and prognosis. Cancer Lett. 2004, 208 (1): 1-33. 10.1016/j.canlet.2004.02.009.CrossRefPubMed
13.
go back to reference Slattery ML, Sweeney C, Murtaugh M, Ma KN, Wolff RK, Potter JD, Caan BJ, Samowitz W: Associations between ERalpha, ERbeta, and AR genotypes and colon and rectal cancer. Cancer Epidemiol Biomarkers Prev. 2005, 14 (12): 2936-2942. 10.1158/1055-9965.EPI-05-0514.CrossRefPubMed Slattery ML, Sweeney C, Murtaugh M, Ma KN, Wolff RK, Potter JD, Caan BJ, Samowitz W: Associations between ERalpha, ERbeta, and AR genotypes and colon and rectal cancer. Cancer Epidemiol Biomarkers Prev. 2005, 14 (12): 2936-2942. 10.1158/1055-9965.EPI-05-0514.CrossRefPubMed
14.
go back to reference Buck MB, Knabbe C: TGF-beta signaling in breast cancer. Ann N Y Acad Sci. 2006, 1089: 119-126. 10.1196/annals.1386.024.CrossRefPubMed Buck MB, Knabbe C: TGF-beta signaling in breast cancer. Ann N Y Acad Sci. 2006, 1089: 119-126. 10.1196/annals.1386.024.CrossRefPubMed
15.
go back to reference Watson MA, Gay L, Stebbings WS, Speakman CT, Bingham SA, Loktionov A: Apolipoprotein E gene polymorphism and colorectal cancer: gender-specific modulation of risk and prognosis. Clin Sci (Lond). 2003, 104 (5): 537-545. 10.1042/CS20020329.CrossRef Watson MA, Gay L, Stebbings WS, Speakman CT, Bingham SA, Loktionov A: Apolipoprotein E gene polymorphism and colorectal cancer: gender-specific modulation of risk and prognosis. Clin Sci (Lond). 2003, 104 (5): 537-545. 10.1042/CS20020329.CrossRef
16.
go back to reference Bae SJ, Kim JW, Kang H, Hwang SG, Oh D, Kim NK: Gender-specific association between polymorphism of vascular endothelial growth factor (VEGF 936 C>T) gene and colon cancer in Korea. Anticancer Res. 2008, 28 (2B): 1271-1276.PubMed Bae SJ, Kim JW, Kang H, Hwang SG, Oh D, Kim NK: Gender-specific association between polymorphism of vascular endothelial growth factor (VEGF 936 C>T) gene and colon cancer in Korea. Anticancer Res. 2008, 28 (2B): 1271-1276.PubMed
17.
go back to reference Press OA, Zhang W, Gordon MA, Yang D, Lurje G, Iqbal S, El-Khoueiry A, Lenz HJ: Gender-related survival differences associated with EGFR polymorphisms in metastatic colon cancer. Cancer Res. 2008, 68 (8): 3037-3042. 10.1158/0008-5472.CAN-07-2718.CrossRefPubMed Press OA, Zhang W, Gordon MA, Yang D, Lurje G, Iqbal S, El-Khoueiry A, Lenz HJ: Gender-related survival differences associated with EGFR polymorphisms in metastatic colon cancer. Cancer Res. 2008, 68 (8): 3037-3042. 10.1158/0008-5472.CAN-07-2718.CrossRefPubMed
18.
go back to reference Wang JM, Irwin RW, Brinton RD: Activation of estrogen receptor alpha increases and estrogen receptor beta decreases apolipoprotein E expression in hippocampus in vitro and in vivo. Proc Natl Acad Sci USA. 2006, 103 (45): 16983-16988. 10.1073/pnas.0608128103.CrossRefPubMedPubMedCentral Wang JM, Irwin RW, Brinton RD: Activation of estrogen receptor alpha increases and estrogen receptor beta decreases apolipoprotein E expression in hippocampus in vitro and in vivo. Proc Natl Acad Sci USA. 2006, 103 (45): 16983-16988. 10.1073/pnas.0608128103.CrossRefPubMedPubMedCentral
19.
go back to reference Ruohola JK, Valve EM, Karkkainen MJ, Joukov V, Alitalo K, Härkönen PL: Vascular endothelial growth factors are differentially regulated by steroid hormones and antiestrogens in breast cancer cells. Mol Cell Endocrinol. 1999, 149 (1-2): 29-40. 10.1016/S0303-7207(99)00003-9.CrossRefPubMed Ruohola JK, Valve EM, Karkkainen MJ, Joukov V, Alitalo K, Härkönen PL: Vascular endothelial growth factors are differentially regulated by steroid hormones and antiestrogens in breast cancer cells. Mol Cell Endocrinol. 1999, 149 (1-2): 29-40. 10.1016/S0303-7207(99)00003-9.CrossRefPubMed
21.
go back to reference Marchini J, Cardon LR, Phillips MS, Donnelly P: The effects of human population structure on large genetic association studies. Nat Genet. 2004, 36 (5): 512-517. 10.1038/ng1337.CrossRefPubMed Marchini J, Cardon LR, Phillips MS, Donnelly P: The effects of human population structure on large genetic association studies. Nat Genet. 2004, 36 (5): 512-517. 10.1038/ng1337.CrossRefPubMed
22.
go back to reference Pritchard JK, Cox NJ: The allelic architecture of human disease genes: common disease-common variant...or not?. Hum Mol Genet. 2002, 11 (20): 2417-2423. 10.1093/hmg/11.20.2417.CrossRefPubMed Pritchard JK, Cox NJ: The allelic architecture of human disease genes: common disease-common variant...or not?. Hum Mol Genet. 2002, 11 (20): 2417-2423. 10.1093/hmg/11.20.2417.CrossRefPubMed
23.
go back to reference Markey MP, Graff J, Carter J, Chen T: Alternative splicing of a cancer-associated intronic variant of TGFBR1 in cancer cell lines. Proc Amer Assoc Cancer Research. 2006, 47: 2475- Markey MP, Graff J, Carter J, Chen T: Alternative splicing of a cancer-associated intronic variant of TGFBR1 in cancer cell lines. Proc Amer Assoc Cancer Research. 2006, 47: 2475-
24.
go back to reference Valle L, Serena-Acedo T, Liyanarachchi S, Hampel H, Comeras I, Li Z, Zeng Q, Zhang HT, Pennison MJ, Sadim M, Pasche B, Tanner SM, de la Chapelle A: Germline allele-specific expression of TGFBR1 confers an increased risk of colorectal cancer. Science. 2008, 321 (5894): 1361-1365. 10.1126/science.1159397.CrossRefPubMedPubMedCentral Valle L, Serena-Acedo T, Liyanarachchi S, Hampel H, Comeras I, Li Z, Zeng Q, Zhang HT, Pennison MJ, Sadim M, Pasche B, Tanner SM, de la Chapelle A: Germline allele-specific expression of TGFBR1 confers an increased risk of colorectal cancer. Science. 2008, 321 (5894): 1361-1365. 10.1126/science.1159397.CrossRefPubMedPubMedCentral
Metadata
Title
The Int7G24A variant of transforming growth factor-beta receptor type I is a risk factor for colorectal cancer in the male Spanish population: a case-control study
Authors
Adela Castillejo
Trinidad Mata-Balaguer
Carla Guarinos
María-Isabel Castillejo
Ana Martínez-Cantó
Víctor-Manuel Barberá
Paola Montenegro
Enrique Ochoa
Rafael Lázaro
Carmen Guillén-Ponce
Alfredo Carrato
José-Luís Soto
Publication date
01-12-2009
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2009
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-9-406

Other articles of this Issue 1/2009

BMC Cancer 1/2009 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine