CHEK2, MGMT, SULT1E1 and SULT1A1 polymorphisms and endometrial cancer risk

Tracy A. O'Mara; Kaltin Ferguson; Paul Fahey; Louise Marquart; Hannah P. Yang; Jolanta Lissowska; Stephen Chanock; Montserrat Garcia-Closas; Deborah J. Thompson; Catherine S. Healey; Alison M. Dunning; Douglas F. Easton; Penelope M. Webb; Amanda B. Spurdle; J. Young; L. McQuire; S. Baron-Hay; D. Bell; A. Bonaventura; A. Brand; S. Braye; J. Carter; F. Chan; C. Dalrymple; A. Ferrier; G. Gard; N. Hacker; R. Hogg; R. Houghton; D. Marsden; K. McIlroy; G. Otton; S. Pather; A. Proietto; G. Robertson; J. Scurry; R. Sharma; G. Wain; F. Wong; J. Armes; A. Crandon; M. Cummings; R. Land; J. Nicklin; L. Perrin; A. Obermair; B. Ward; M. Davy; T. Dodd; J. Miller; M. Oehler; S. Paramasivum; J. Pierides; F. Whitehead; P. Blomfield; D. Challis; D. Neesham; J. Pyman; M. Quinn; R. Rome; M. Weitzer; B. Brennan; I. Hammond; Y. Leung; A. McCartney; C. Stewart; J. Thompson; S. O'Brien; S. Moore; M. Walsh; R. Cicero; L. Green; J. Griffith; L. Jackman; B. Ranieri; M. O'Brien; P. Schultz; B. Alexander; C. Baxter; H. Croy; A. Fitzgerald; E. Herron; C. Hill; M. Jones; J. Maidens; A. Marshall; K. Martin; J. Mayhew; E. Minehan; D. Roffe; H. Shirley; H. Steane; A. Stenlake; A. Ward; S. Webb; J. White

doi:10.1375/twin.14.4.328

CHEK2, MGMT, SULT1E1 and SULT1A1 polymorphisms and endometrial cancer risk

Tracy A. O'Mara, Kaltin Ferguson, Paul Fahey, Louise Marquart, Hannah P. Yang, Jolanta Lissowska, Stephen Chanock, Montserrat Garcia-Closas, Deborah J. Thompson, Catherine S. Healey, Alison M. Dunning, Douglas F. Easton, Penelope M. Webb, Amanda B. Spurdle, J. Young, L. McQuire, S. Baron-Hay, D. Bell, A. Bonaventura, A. BrandS. Braye, J. Carter, F. Chan, C. Dalrymple, A. Ferrier, G. Gard, N. Hacker, R. Hogg, R. Houghton, D. Marsden, K. McIlroy, G. Otton, S. Pather, A. Proietto, G. Robertson, J. Scurry, R. Sharma, G. Wain, F. Wong, J. Armes, A. Crandon, M. Cummings, R. Land, J. Nicklin, L. Perrin, A. Obermair, B. Ward, M. Davy, T. Dodd, J. Miller, M. Oehler, S. Paramasivum, J. Pierides, F. Whitehead, P. Blomfield, D. Challis, D. Neesham, J. Pyman, M. Quinn, R. Rome, M. Weitzer, B. Brennan, I. Hammond, Y. Leung, A. McCartney, C. Stewart, J. Thompson, S. O'Brien, S. Moore, M. Walsh, R. Cicero, L. Green, J. Griffith, L. Jackman, B. Ranieri, M. O'Brien, P. Schultz, B. Alexander, C. Baxter, H. Croy, A. Fitzgerald, E. Herron, C. Hill, M. Jones, J. Maidens, A. Marshall, K. Martin, J. Mayhew, E. Minehan, D. Roffe, H. Shirley, H. Steane, A. Stenlake, A. Ward, S. Webb, J. White

Environmental Health Sciences

Research output: Contribution to journal › Article › peer-review

14 Scopus citations

Abstract

Several single nucleotide polymorphisms (SNPs) in candidate genes of DNA repair and hormone pathways have been reported to be associated with endometrial cancer risk. We sought to confirm these associations in two endometrial cancer case-control sample sets and used additional data from an existing genome-wide association study to prioritize an additional SNP for further study. Five SNPs from the CHEK2, MGMT, SULT1E1 and SULT1A1 genes, genotyped in a total of 1597 cases and 1507 controls from two case-control studies, the Australian National Endometrial Cancer Study and the Polish Endometrial Cancer Study, were assessed for association with endometrial cancer risk using logistic regression analysis. Imputed data was drawn for CHEK2 rs8135424 for 666 cases from the Study of Epidemiology and Risk factors in Cancer Heredity study and 5190 controls from the Wellcome Trust Case Control Consortium. We observed no association between SNPs in the MGMT, SULT1E1 and SULT1A1 genes and endometrial cancer risk. The A allele of the rs8135424 CHEK2 SNP was associated with decreased risk of endometrial cancer (adjusted per-allele OR 0.83; 95%CI 0.70-0.98; p = .03) however this finding was opposite to that previously published. Imputed data for CHEK2 rs8135424 supported the direction of effect reported in this study (OR 0.85; 95% CI 0.65-1.10). Previously reported endometrial cancer risk associations with SNPs from in genes involved in estrogen metabolism and DNA repair were not replicated in our larger study population. This study highlights the need for replication of candidate gene SNP studies using large sample groups, to confirm risk associations and better prioritize downstream studies to assess the causal relationship between genetic variants and cancer risk. Our findings suggest that the CHEK2 SNP rs8135424 be prioritized for further study as a genetic factor associated with risk of endometrial cancer.

Original language	English (US)
Pages (from-to)	328-332
Number of pages	5
Journal	Twin Research and Human Genetics
Volume	14
Issue number	4
DOIs	https://doi.org/10.1375/twin.14.4.328
State	Published - 2011

Bibliographical note

Funding Information:
ANECS was supported by project grants from the National Health and Medical Research Council (NHMRC) of Australia (ID#339435), The Cancer Council Queensland (ID#4196615) and Cancer Council Tasmania (ID#403031 and ID#457636). ABS and PMW are supported by NHMRC Senior Research Fellowships. TOM is supported by an Australian Postgraduate Award, an Institute of Health and Biomedical Innovation PhD Top-Up and a Smart State PhD Award. PECS was funded by the intramural research program at the US National Cancer Institute, Division of Cancer Epidemiology and Genetics in the Hormonal and Reproductive Epidemiology Branch. SEARCH was funded by Cancer Research UK grants [C490/A11021, C8197/A10123, C1287/A7497, C1287/A10118], BCC grant [2077NovPR17] and EU FP7 COGS [HEALTH-F2-2009-223175]. AMD was supported by Cancer Research Grant [C8197/A10865] and The Joseph Mitchell Trust.

Keywords

CHEK2
Endometrial cancer
MGMT
SULT1A1
SULT1E1
Single nucleotide polymorphism

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1375/twin.14.4.328

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O'Mara, T. A., Ferguson, K., Fahey, P., Marquart, L., Yang, H. P., Lissowska, J., Chanock, S., Garcia-Closas, M., Thompson, D. J., Healey, C. S., Dunning, A. M., Easton, D. F., Webb, P. M., Spurdle, A. B., Young, J., McQuire, L., Baron-Hay, S., Bell, D., Bonaventura, A., ... White, J. (2011). CHEK2, MGMT, SULT1E1 and SULT1A1 polymorphisms and endometrial cancer risk. Twin Research and Human Genetics, 14(4), 328-332. https://doi.org/10.1375/twin.14.4.328

O'Mara, TA, Ferguson, K, Fahey, P, Marquart, L, Yang, HP, Lissowska, J, Chanock, S, Garcia-Closas, M, Thompson, DJ, Healey, CS, Dunning, AM, Easton, DF, Webb, PM, Spurdle, AB, Young, J, McQuire, L, Baron-Hay, S, Bell, D, Bonaventura, A, Brand, A, Braye, S, Carter, J, Chan, F, Dalrymple, C, Ferrier, A, Gard, G, Hacker, N, Hogg, R, Houghton, R, Marsden, D, McIlroy, K, Otton, G, Pather, S, Proietto, A, Robertson, G, Scurry, J, Sharma, R, Wain, G, Wong, F, Armes, J, Crandon, A, Cummings, M, Land, R, Nicklin, J, Perrin, L, Obermair, A, Ward, B, Davy, M, Dodd, T, Miller, J, Oehler, M, Paramasivum, S, Pierides, J, Whitehead, F, Blomfield, P, Challis, D, Neesham, D, Pyman, J, Quinn, M, Rome, R, Weitzer, M, Brennan, B, Hammond, I, Leung, Y, McCartney, A, Stewart, C, Thompson, J, O'Brien, S, Moore, S, Walsh, M, Cicero, R, Green, L, Griffith, J, Jackman, L, Ranieri, B, O'Brien, M, Schultz, P, Alexander, B, Baxter, C, Croy, H, Fitzgerald, A, Herron, E, Hill, C, Jones, M, Maidens, J, Marshall, A, Martin, K, Mayhew, J, Minehan, E, Roffe, D, Shirley, H, Steane, H, Stenlake, A, Ward, A, Webb, S & White, J 2011, 'CHEK2, MGMT, SULT1E1 and SULT1A1 polymorphisms and endometrial cancer risk', Twin Research and Human Genetics, vol. 14, no. 4, pp. 328-332. https://doi.org/10.1375/twin.14.4.328

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title = "CHEK2, MGMT, SULT1E1 and SULT1A1 polymorphisms and endometrial cancer risk",

abstract = "Several single nucleotide polymorphisms (SNPs) in candidate genes of DNA repair and hormone pathways have been reported to be associated with endometrial cancer risk. We sought to confirm these associations in two endometrial cancer case-control sample sets and used additional data from an existing genome-wide association study to prioritize an additional SNP for further study. Five SNPs from the CHEK2, MGMT, SULT1E1 and SULT1A1 genes, genotyped in a total of 1597 cases and 1507 controls from two case-control studies, the Australian National Endometrial Cancer Study and the Polish Endometrial Cancer Study, were assessed for association with endometrial cancer risk using logistic regression analysis. Imputed data was drawn for CHEK2 rs8135424 for 666 cases from the Study of Epidemiology and Risk factors in Cancer Heredity study and 5190 controls from the Wellcome Trust Case Control Consortium. We observed no association between SNPs in the MGMT, SULT1E1 and SULT1A1 genes and endometrial cancer risk. The A allele of the rs8135424 CHEK2 SNP was associated with decreased risk of endometrial cancer (adjusted per-allele OR 0.83; 95%CI 0.70-0.98; p = .03) however this finding was opposite to that previously published. Imputed data for CHEK2 rs8135424 supported the direction of effect reported in this study (OR 0.85; 95% CI 0.65-1.10). Previously reported endometrial cancer risk associations with SNPs from in genes involved in estrogen metabolism and DNA repair were not replicated in our larger study population. This study highlights the need for replication of candidate gene SNP studies using large sample groups, to confirm risk associations and better prioritize downstream studies to assess the causal relationship between genetic variants and cancer risk. Our findings suggest that the CHEK2 SNP rs8135424 be prioritized for further study as a genetic factor associated with risk of endometrial cancer.",

keywords = "CHEK2, Endometrial cancer, MGMT, SULT1A1, SULT1E1, Single nucleotide polymorphism",

author = "O'Mara, {Tracy A.} and Kaltin Ferguson and Paul Fahey and Louise Marquart and Yang, {Hannah P.} and Jolanta Lissowska and Stephen Chanock and Montserrat Garcia-Closas and Thompson, {Deborah J.} and Healey, {Catherine S.} and Dunning, {Alison M.} and Easton, {Douglas F.} and Webb, {Penelope M.} and Spurdle, {Amanda B.} and J. Young and L. McQuire and S. Baron-Hay and D. Bell and A. Bonaventura and A. Brand and S. Braye and J. Carter and F. Chan and C. Dalrymple and A. Ferrier and G. Gard and N. Hacker and R. Hogg and R. Houghton and D. Marsden and K. McIlroy and G. Otton and S. Pather and A. Proietto and G. Robertson and J. Scurry and R. Sharma and G. Wain and F. Wong and J. Armes and A. Crandon and M. Cummings and R. Land and J. Nicklin and L. Perrin and A. Obermair and B. Ward and M. Davy and T. Dodd and J. Miller and M. Oehler and S. Paramasivum and J. Pierides and F. Whitehead and P. Blomfield and D. Challis and D. Neesham and J. Pyman and M. Quinn and R. Rome and M. Weitzer and B. Brennan and I. Hammond and Y. Leung and A. McCartney and C. Stewart and J. Thompson and S. O'Brien and S. Moore and M. Walsh and R. Cicero and L. Green and J. Griffith and L. Jackman and B. Ranieri and M. O'Brien and P. Schultz and B. Alexander and C. Baxter and H. Croy and A. Fitzgerald and E. Herron and C. Hill and M. Jones and J. Maidens and A. Marshall and K. Martin and J. Mayhew and E. Minehan and D. Roffe and H. Shirley and H. Steane and A. Stenlake and A. Ward and S. Webb and J. White",

note = "Funding Information: ANECS was supported by project grants from the National Health and Medical Research Council (NHMRC) of Australia (ID#339435), The Cancer Council Queensland (ID#4196615) and Cancer Council Tasmania (ID#403031 and ID#457636). ABS and PMW are supported by NHMRC Senior Research Fellowships. TOM is supported by an Australian Postgraduate Award, an Institute of Health and Biomedical Innovation PhD Top-Up and a Smart State PhD Award. PECS was funded by the intramural research program at the US National Cancer Institute, Division of Cancer Epidemiology and Genetics in the Hormonal and Reproductive Epidemiology Branch. SEARCH was funded by Cancer Research UK grants [C490/A11021, C8197/A10123, C1287/A7497, C1287/A10118], BCC grant [2077NovPR17] and EU FP7 COGS [HEALTH-F2-2009-223175]. AMD was supported by Cancer Research Grant [C8197/A10865] and The Joseph Mitchell Trust.",

year = "2011",

doi = "10.1375/twin.14.4.328",

language = "English (US)",

volume = "14",

pages = "328--332",

journal = "Twin Research and Human Genetics",

issn = "1832-4274",

publisher = "Australian Academic Press",

number = "4",

}

TY - JOUR

T1 - CHEK2, MGMT, SULT1E1 and SULT1A1 polymorphisms and endometrial cancer risk

AU - O'Mara, Tracy A.

AU - Ferguson, Kaltin

AU - Fahey, Paul

AU - Marquart, Louise

AU - Yang, Hannah P.

AU - Lissowska, Jolanta

AU - Chanock, Stephen

AU - Garcia-Closas, Montserrat

AU - Thompson, Deborah J.

AU - Healey, Catherine S.

AU - Dunning, Alison M.

AU - Easton, Douglas F.

AU - Webb, Penelope M.

AU - Spurdle, Amanda B.

AU - Young, J.

AU - McQuire, L.

AU - Baron-Hay, S.

AU - Bell, D.

AU - Bonaventura, A.

AU - Brand, A.

AU - Braye, S.

AU - Carter, J.

AU - Chan, F.

AU - Dalrymple, C.

AU - Ferrier, A.

AU - Gard, G.

AU - Hacker, N.

AU - Hogg, R.

AU - Houghton, R.

AU - Marsden, D.

AU - McIlroy, K.

AU - Otton, G.

AU - Pather, S.

AU - Proietto, A.

AU - Robertson, G.

AU - Scurry, J.

AU - Sharma, R.

AU - Wain, G.

AU - Wong, F.

AU - Armes, J.

AU - Crandon, A.

AU - Cummings, M.

AU - Land, R.

AU - Nicklin, J.

AU - Perrin, L.

AU - Obermair, A.

AU - Ward, B.

AU - Davy, M.

AU - Dodd, T.

AU - Miller, J.

AU - Oehler, M.

AU - Paramasivum, S.

AU - Pierides, J.

AU - Whitehead, F.

AU - Blomfield, P.

AU - Challis, D.

AU - Neesham, D.

AU - Pyman, J.

AU - Quinn, M.

AU - Rome, R.

AU - Weitzer, M.

AU - Brennan, B.

AU - Hammond, I.

AU - Leung, Y.

AU - McCartney, A.

AU - Stewart, C.

AU - Thompson, J.

AU - O'Brien, S.

AU - Moore, S.

AU - Walsh, M.

AU - Cicero, R.

AU - Green, L.

AU - Griffith, J.

AU - Jackman, L.

AU - Ranieri, B.

AU - O'Brien, M.

AU - Schultz, P.

AU - Alexander, B.

AU - Baxter, C.

AU - Croy, H.

AU - Fitzgerald, A.

AU - Herron, E.

AU - Hill, C.

AU - Jones, M.

AU - Maidens, J.

AU - Marshall, A.

AU - Martin, K.

AU - Mayhew, J.

AU - Minehan, E.

AU - Roffe, D.

AU - Shirley, H.

AU - Steane, H.

AU - Stenlake, A.

AU - Ward, A.

AU - Webb, S.

AU - White, J.

N1 - Funding Information: ANECS was supported by project grants from the National Health and Medical Research Council (NHMRC) of Australia (ID#339435), The Cancer Council Queensland (ID#4196615) and Cancer Council Tasmania (ID#403031 and ID#457636). ABS and PMW are supported by NHMRC Senior Research Fellowships. TOM is supported by an Australian Postgraduate Award, an Institute of Health and Biomedical Innovation PhD Top-Up and a Smart State PhD Award. PECS was funded by the intramural research program at the US National Cancer Institute, Division of Cancer Epidemiology and Genetics in the Hormonal and Reproductive Epidemiology Branch. SEARCH was funded by Cancer Research UK grants [C490/A11021, C8197/A10123, C1287/A7497, C1287/A10118], BCC grant [2077NovPR17] and EU FP7 COGS [HEALTH-F2-2009-223175]. AMD was supported by Cancer Research Grant [C8197/A10865] and The Joseph Mitchell Trust.

PY - 2011

Y1 - 2011

N2 - Several single nucleotide polymorphisms (SNPs) in candidate genes of DNA repair and hormone pathways have been reported to be associated with endometrial cancer risk. We sought to confirm these associations in two endometrial cancer case-control sample sets and used additional data from an existing genome-wide association study to prioritize an additional SNP for further study. Five SNPs from the CHEK2, MGMT, SULT1E1 and SULT1A1 genes, genotyped in a total of 1597 cases and 1507 controls from two case-control studies, the Australian National Endometrial Cancer Study and the Polish Endometrial Cancer Study, were assessed for association with endometrial cancer risk using logistic regression analysis. Imputed data was drawn for CHEK2 rs8135424 for 666 cases from the Study of Epidemiology and Risk factors in Cancer Heredity study and 5190 controls from the Wellcome Trust Case Control Consortium. We observed no association between SNPs in the MGMT, SULT1E1 and SULT1A1 genes and endometrial cancer risk. The A allele of the rs8135424 CHEK2 SNP was associated with decreased risk of endometrial cancer (adjusted per-allele OR 0.83; 95%CI 0.70-0.98; p = .03) however this finding was opposite to that previously published. Imputed data for CHEK2 rs8135424 supported the direction of effect reported in this study (OR 0.85; 95% CI 0.65-1.10). Previously reported endometrial cancer risk associations with SNPs from in genes involved in estrogen metabolism and DNA repair were not replicated in our larger study population. This study highlights the need for replication of candidate gene SNP studies using large sample groups, to confirm risk associations and better prioritize downstream studies to assess the causal relationship between genetic variants and cancer risk. Our findings suggest that the CHEK2 SNP rs8135424 be prioritized for further study as a genetic factor associated with risk of endometrial cancer.

AB - Several single nucleotide polymorphisms (SNPs) in candidate genes of DNA repair and hormone pathways have been reported to be associated with endometrial cancer risk. We sought to confirm these associations in two endometrial cancer case-control sample sets and used additional data from an existing genome-wide association study to prioritize an additional SNP for further study. Five SNPs from the CHEK2, MGMT, SULT1E1 and SULT1A1 genes, genotyped in a total of 1597 cases and 1507 controls from two case-control studies, the Australian National Endometrial Cancer Study and the Polish Endometrial Cancer Study, were assessed for association with endometrial cancer risk using logistic regression analysis. Imputed data was drawn for CHEK2 rs8135424 for 666 cases from the Study of Epidemiology and Risk factors in Cancer Heredity study and 5190 controls from the Wellcome Trust Case Control Consortium. We observed no association between SNPs in the MGMT, SULT1E1 and SULT1A1 genes and endometrial cancer risk. The A allele of the rs8135424 CHEK2 SNP was associated with decreased risk of endometrial cancer (adjusted per-allele OR 0.83; 95%CI 0.70-0.98; p = .03) however this finding was opposite to that previously published. Imputed data for CHEK2 rs8135424 supported the direction of effect reported in this study (OR 0.85; 95% CI 0.65-1.10). Previously reported endometrial cancer risk associations with SNPs from in genes involved in estrogen metabolism and DNA repair were not replicated in our larger study population. This study highlights the need for replication of candidate gene SNP studies using large sample groups, to confirm risk associations and better prioritize downstream studies to assess the causal relationship between genetic variants and cancer risk. Our findings suggest that the CHEK2 SNP rs8135424 be prioritized for further study as a genetic factor associated with risk of endometrial cancer.

KW - CHEK2

KW - Endometrial cancer

KW - MGMT

KW - SULT1A1

KW - SULT1E1

KW - Single nucleotide polymorphism

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DO - 10.1375/twin.14.4.328

M3 - Article

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AN - SCOPUS:80051505316

SN - 1832-4274

VL - 14

SP - 328

EP - 332

JO - Twin Research and Human Genetics

JF - Twin Research and Human Genetics

IS - 4

ER -

CHEK2, MGMT, SULT1E1 and SULT1A1 polymorphisms and endometrial cancer risk

Abstract

Bibliographical note

Keywords

UN SDGs

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