Cross-cancer pleiotropic analysis of endometrial cancer: PAGE and E2C2 consortia

Veronica Wendy Setiawan; Fredrick Schumacher; Jennifer Prescott; Jeffrey Haessler; Jennifer Malinowski; Nicolas Wentzensen; Hannah Yang; Stephen Chanock; Louise Brinton; Patricia Hartge; Jolanta Lissowska; S. Lani Park; Iona Cheng; William S. Bush; Dana C. Crawford; Giske Ursin; Pamela Horn-Ross; Leslie Bernstein; Lingeng Lu; Harvey Risch; Herbert Yu; Lori C. Sakoda; Jennifer Doherty; Chu Chen; Rebecca Jackson; Shagufta Yasmeen; Michele Cote; Jonathan M. Kocarnik; Ulrike Peters; Peter Kraft; Immaculata De Vivo; Christopher A. Haiman; Charles Kooperberg; Loic Le Marchand

doi:10.1093/carcin/bgu107

Cross-cancer pleiotropic analysis of endometrial cancer: PAGE and E2C2 consortia

Veronica Wendy Setiawan, Fredrick Schumacher, Jennifer Prescott, Jeffrey Haessler, Jennifer Malinowski, Nicolas Wentzensen, Hannah Yang, Stephen Chanock, Louise Brinton, Patricia Hartge, Jolanta Lissowska, S. Lani Park, Iona Cheng, William S. Bush, Dana C. Crawford, Giske Ursin, Pamela Horn-Ross, Leslie Bernstein, Lingeng Lu, Harvey RischHerbert Yu, Lori C. Sakoda, Jennifer Doherty, Chu Chen, Rebecca Jackson, Shagufta Yasmeen, Michele Cote, Jonathan M. Kocarnik, Ulrike Peters, Peter Kraft, Immaculata De Vivo, Christopher A. Haiman, Charles Kooperberg, Loic Le Marchand

School of Medicine

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

14 Scopus citations

Abstract

Genome-wide association studies (GWAS) have identified a large number of cancer-associated single nucleotide polymorphisms (SNPs), several of which have been associated with multiple cancer sites suggesting pleiotropic effects and shared biological mechanisms across some cancers. We hypothesized that SNPs associated with other cancers may be additionally associated with endometrial cancer. We examined 213 SNPs previously associated with 14 other cancers for their associations with endometrial cancer in 3758 endometrial cancer cases and 5966 controls of European ancestry from two consortia: Population Architecture Using Genomics and Epidemiology and the Epidemiology of Endometrial Cancer Consortium. Study-specific logistic regression estimates adjusted for age, body mass index and the most significant principal components of genetic ancestry were combined using fixedeffect meta-analysis to evaluate the association between each SNP and endometrial cancer risk. A Bonferroni-corrected P value of 2.35 × 10^-4 was used to determine statistical significance of the associations. SNP rs7679673, ~6.3 kb upstream of TET2 and previously reported to be associated with prostate cancer risk, was associated with endometrial cancer risk in the direction opposite to that for prostate cancer [meta-analysis odds ratio = 0.87 (per copy of the C allele), 95% confidence interval = 0.81, 0.93; P = 7.37 × 10^-5] with no evidence of heterogeneity across studies (P heterogeneity = 0.66). This pleiotropic analysis is the first to suggest TET2 as a susceptibility locus for endometrial cancer.

Original language	English (US)
Article number	bgu107
Pages (from-to)	2068-2073
Number of pages	6
Journal	Carcinogenesis
Volume	35
Issue number	9
DOIs	https://doi.org/10.1093/carcin/bgu107
State	Published - Sep 2014

ASJC Scopus subject areas

Cancer Research

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10.1093/carcin/bgu107

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Setiawan, V. W., Schumacher, F., Prescott, J., Haessler, J., Malinowski, J., Wentzensen, N., Yang, H., Chanock, S., Brinton, L., Hartge, P., Lissowska, J., Lani Park, S., Cheng, I., Bush, W. S., Crawford, D. C., Ursin, G., Horn-Ross, P., Bernstein, L., Lu, L., ... Le Marchand, L. (2014). Cross-cancer pleiotropic analysis of endometrial cancer: PAGE and E2C2 consortia. Carcinogenesis, 35(9), 2068-2073. Article bgu107. https://doi.org/10.1093/carcin/bgu107

Setiawan, VW, Schumacher, F, Prescott, J, Haessler, J, Malinowski, J, Wentzensen, N, Yang, H, Chanock, S, Brinton, L, Hartge, P, Lissowska, J, Lani Park, S, Cheng, I, Bush, WS, Crawford, DC, Ursin, G, Horn-Ross, P, Bernstein, L, Lu, L, Risch, H, Yu, H, Sakoda, LC, Doherty, J, Chen, C, Jackson, R, Yasmeen, S, Cote, M, Kocarnik, JM, Peters, U, Kraft, P, De Vivo, I, Haiman, CA, Kooperberg, C & Le Marchand, L 2014, 'Cross-cancer pleiotropic analysis of endometrial cancer: PAGE and E2C2 consortia', Carcinogenesis, vol. 35, no. 9, bgu107, pp. 2068-2073. https://doi.org/10.1093/carcin/bgu107

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title = "Cross-cancer pleiotropic analysis of endometrial cancer: PAGE and E2C2 consortia",

abstract = "Genome-wide association studies (GWAS) have identified a large number of cancer-associated single nucleotide polymorphisms (SNPs), several of which have been associated with multiple cancer sites suggesting pleiotropic effects and shared biological mechanisms across some cancers. We hypothesized that SNPs associated with other cancers may be additionally associated with endometrial cancer. We examined 213 SNPs previously associated with 14 other cancers for their associations with endometrial cancer in 3758 endometrial cancer cases and 5966 controls of European ancestry from two consortia: Population Architecture Using Genomics and Epidemiology and the Epidemiology of Endometrial Cancer Consortium. Study-specific logistic regression estimates adjusted for age, body mass index and the most significant principal components of genetic ancestry were combined using fixedeffect meta-analysis to evaluate the association between each SNP and endometrial cancer risk. A Bonferroni-corrected P value of 2.35 × 10-4 was used to determine statistical significance of the associations. SNP rs7679673, ~6.3 kb upstream of TET2 and previously reported to be associated with prostate cancer risk, was associated with endometrial cancer risk in the direction opposite to that for prostate cancer [meta-analysis odds ratio = 0.87 (per copy of the C allele), 95% confidence interval = 0.81, 0.93; P = 7.37 × 10-5] with no evidence of heterogeneity across studies (P heterogeneity = 0.66). This pleiotropic analysis is the first to suggest TET2 as a susceptibility locus for endometrial cancer.",

author = "Setiawan, {Veronica Wendy} and Fredrick Schumacher and Jennifer Prescott and Jeffrey Haessler and Jennifer Malinowski and Nicolas Wentzensen and Hannah Yang and Stephen Chanock and Louise Brinton and Patricia Hartge and Jolanta Lissowska and {Lani Park}, S. and Iona Cheng and Bush, {William S.} and Crawford, {Dana C.} and Giske Ursin and Pamela Horn-Ross and Leslie Bernstein and Lingeng Lu and Harvey Risch and Herbert Yu and Sakoda, {Lori C.} and Jennifer Doherty and Chu Chen and Rebecca Jackson and Shagufta Yasmeen and Michele Cote and Kocarnik, {Jonathan M.} and Ulrike Peters and Peter Kraft and {De Vivo}, Immaculata and Haiman, {Christopher A.} and Charles Kooperberg and {Le Marchand}, Loic",

year = "2014",

month = sep,

doi = "10.1093/carcin/bgu107",

language = "English (US)",

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journal = "Carcinogenesis",

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T2 - PAGE and E2C2 consortia

AU - Setiawan, Veronica Wendy

AU - Schumacher, Fredrick

AU - Prescott, Jennifer

AU - Haessler, Jeffrey

AU - Malinowski, Jennifer

AU - Wentzensen, Nicolas

AU - Yang, Hannah

AU - Chanock, Stephen

AU - Brinton, Louise

AU - Hartge, Patricia

AU - Lissowska, Jolanta

AU - Lani Park, S.

AU - Cheng, Iona

AU - Bush, William S.

AU - Crawford, Dana C.

AU - Ursin, Giske

AU - Horn-Ross, Pamela

AU - Bernstein, Leslie

AU - Lu, Lingeng

AU - Risch, Harvey

AU - Yu, Herbert

AU - Sakoda, Lori C.

AU - Doherty, Jennifer

AU - Chen, Chu

AU - Jackson, Rebecca

AU - Yasmeen, Shagufta

AU - Cote, Michele

AU - Kocarnik, Jonathan M.

AU - Peters, Ulrike

AU - Kraft, Peter

AU - De Vivo, Immaculata

AU - Haiman, Christopher A.

AU - Kooperberg, Charles

AU - Le Marchand, Loic

PY - 2014/9

Y1 - 2014/9

N2 - Genome-wide association studies (GWAS) have identified a large number of cancer-associated single nucleotide polymorphisms (SNPs), several of which have been associated with multiple cancer sites suggesting pleiotropic effects and shared biological mechanisms across some cancers. We hypothesized that SNPs associated with other cancers may be additionally associated with endometrial cancer. We examined 213 SNPs previously associated with 14 other cancers for their associations with endometrial cancer in 3758 endometrial cancer cases and 5966 controls of European ancestry from two consortia: Population Architecture Using Genomics and Epidemiology and the Epidemiology of Endometrial Cancer Consortium. Study-specific logistic regression estimates adjusted for age, body mass index and the most significant principal components of genetic ancestry were combined using fixedeffect meta-analysis to evaluate the association between each SNP and endometrial cancer risk. A Bonferroni-corrected P value of 2.35 × 10-4 was used to determine statistical significance of the associations. SNP rs7679673, ~6.3 kb upstream of TET2 and previously reported to be associated with prostate cancer risk, was associated with endometrial cancer risk in the direction opposite to that for prostate cancer [meta-analysis odds ratio = 0.87 (per copy of the C allele), 95% confidence interval = 0.81, 0.93; P = 7.37 × 10-5] with no evidence of heterogeneity across studies (P heterogeneity = 0.66). This pleiotropic analysis is the first to suggest TET2 as a susceptibility locus for endometrial cancer.

AB - Genome-wide association studies (GWAS) have identified a large number of cancer-associated single nucleotide polymorphisms (SNPs), several of which have been associated with multiple cancer sites suggesting pleiotropic effects and shared biological mechanisms across some cancers. We hypothesized that SNPs associated with other cancers may be additionally associated with endometrial cancer. We examined 213 SNPs previously associated with 14 other cancers for their associations with endometrial cancer in 3758 endometrial cancer cases and 5966 controls of European ancestry from two consortia: Population Architecture Using Genomics and Epidemiology and the Epidemiology of Endometrial Cancer Consortium. Study-specific logistic regression estimates adjusted for age, body mass index and the most significant principal components of genetic ancestry were combined using fixedeffect meta-analysis to evaluate the association between each SNP and endometrial cancer risk. A Bonferroni-corrected P value of 2.35 × 10-4 was used to determine statistical significance of the associations. SNP rs7679673, ~6.3 kb upstream of TET2 and previously reported to be associated with prostate cancer risk, was associated with endometrial cancer risk in the direction opposite to that for prostate cancer [meta-analysis odds ratio = 0.87 (per copy of the C allele), 95% confidence interval = 0.81, 0.93; P = 7.37 × 10-5] with no evidence of heterogeneity across studies (P heterogeneity = 0.66). This pleiotropic analysis is the first to suggest TET2 as a susceptibility locus for endometrial cancer.

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Cross-cancer pleiotropic analysis of endometrial cancer: PAGE and E2C2 consortia

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