Genetic variants in sex hormone metabolic pathway genes and risk of esophageal squamous cell carcinoma

Paula L. Hyland; Neal D. Freedman; Nan Hu; Ze Zhong Tang; Lemin Wang; Chaoyu Wang; Ti Ding; Jin Hu Fan; You Lin Qiao; Asieh Golozar; William Wheeler; Kai Yu; Jeff Yuenger; Laurie Burdett; Stephen J. Chanock; Sanford M. Dawsey; Margaret A. Tucker; Alisa M. Goldstein; Christian C. Abnet; Philip R. Taylor

doi:10.1093/carcin/bgt030

Genetic variants in sex hormone metabolic pathway genes and risk of esophageal squamous cell carcinoma

Paula L. Hyland, Neal D. Freedman, Nan Hu, Ze Zhong Tang, Lemin Wang, Chaoyu Wang, Ti Ding, Jin Hu Fan, You Lin Qiao, Asieh Golozar, William Wheeler, Kai Yu, Jeff Yuenger, Laurie Burdett, Stephen J. Chanock, Sanford M. Dawsey, Margaret A. Tucker, Alisa M. Goldstein, Christian C. Abnet, Philip R. Taylor

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

25 Scopus citations

Abstract

In China, esophageal cancer is the fourth leading cause of cancer death where essentially all cases are histologically esophageal squamous cell carcinoma (ESCC), in contrast to esophageal ade-nocarcinoma in the West. Globally, ESCC is 2.4 times more common among men than women and recently it has been suggested that sex hormones may be associated with the risk of ESCC. We examined the association between genetic variants in sex hormone metabolic genes and ESCC risk in a population from north central China with high-incidence rates. A total of 1026 ESCC cases and 1452 controls were genotyped for 797 unique tag sin-gle-nucleotide polymorphisms (SNPs) in 51 sex hormone metabolic genes. SNP-, gene- and pathway-based associations with ESCC risk were evaluated using unconditional logistic regression adjusted for age, sex and geographical location and the adaptive rank truncated product (ARTP) method. Statistical significance was determined through use of permutation for pathway- and gene-based associations. No associations were observed for the overall sex hormone metabolic pathway (P = 0.14) or subpath-ways (androgen synthesis: P = 0.30, estrogen synthesis: P = 0.15 and estrogen removal: P = 0.19) with risk of ESCC. However, six individual genes (including SULT2B1, CYP1B1, CYP3A7, CYP3A5, SHBG and CYP11A1) were significantly associated with ESCC risk (P < 0.05). Our examination of genetic variation in the sex hormone metabolic pathway is consistent with a potential association with risk of ESCC. These positive findings warrant further evaluation in relation to ESCC risk and replication in other populations.

Original language	English (US)
Pages (from-to)	1062-1068
Number of pages	7
Journal	Carcinogenesis
Volume	34
Issue number	5
DOIs	https://doi.org/10.1093/carcin/bgt030
State	Published - May 2013
Externally published	Yes

ASJC Scopus subject areas

Cancer Research

Access to Document

10.1093/carcin/bgt030

Cite this

Hyland, P. L., Freedman, N. D., Hu, N., Tang, Z. Z., Wang, L., Wang, C., Ding, T., Fan, J. H., Qiao, Y. L., Golozar, A., Wheeler, W., Yu, K., Yuenger, J., Burdett, L., Chanock, S. J., Dawsey, S. M., Tucker, M. A., Goldstein, A. M., Abnet, C. C., & Taylor, P. R. (2013). Genetic variants in sex hormone metabolic pathway genes and risk of esophageal squamous cell carcinoma. Carcinogenesis, 34(5), 1062-1068. https://doi.org/10.1093/carcin/bgt030

Hyland, PL, Freedman, ND, Hu, N, Tang, ZZ, Wang, L, Wang, C, Ding, T, Fan, JH, Qiao, YL, Golozar, A, Wheeler, W, Yu, K, Yuenger, J, Burdett, L, Chanock, SJ, Dawsey, SM, Tucker, MA, Goldstein, AM, Abnet, CC & Taylor, PR 2013, 'Genetic variants in sex hormone metabolic pathway genes and risk of esophageal squamous cell carcinoma', Carcinogenesis, vol. 34, no. 5, pp. 1062-1068. https://doi.org/10.1093/carcin/bgt030

@article{7cfef68356484056a45e80e4a2d1fd4d,

title = "Genetic variants in sex hormone metabolic pathway genes and risk of esophageal squamous cell carcinoma",

abstract = "In China, esophageal cancer is the fourth leading cause of cancer death where essentially all cases are histologically esophageal squamous cell carcinoma (ESCC), in contrast to esophageal ade-nocarcinoma in the West. Globally, ESCC is 2.4 times more common among men than women and recently it has been suggested that sex hormones may be associated with the risk of ESCC. We examined the association between genetic variants in sex hormone metabolic genes and ESCC risk in a population from north central China with high-incidence rates. A total of 1026 ESCC cases and 1452 controls were genotyped for 797 unique tag sin-gle-nucleotide polymorphisms (SNPs) in 51 sex hormone metabolic genes. SNP-, gene- and pathway-based associations with ESCC risk were evaluated using unconditional logistic regression adjusted for age, sex and geographical location and the adaptive rank truncated product (ARTP) method. Statistical significance was determined through use of permutation for pathway- and gene-based associations. No associations were observed for the overall sex hormone metabolic pathway (P = 0.14) or subpath-ways (androgen synthesis: P = 0.30, estrogen synthesis: P = 0.15 and estrogen removal: P = 0.19) with risk of ESCC. However, six individual genes (including SULT2B1, CYP1B1, CYP3A7, CYP3A5, SHBG and CYP11A1) were significantly associated with ESCC risk (P < 0.05). Our examination of genetic variation in the sex hormone metabolic pathway is consistent with a potential association with risk of ESCC. These positive findings warrant further evaluation in relation to ESCC risk and replication in other populations.",

author = "Hyland, {Paula L.} and Freedman, {Neal D.} and Nan Hu and Tang, {Ze Zhong} and Lemin Wang and Chaoyu Wang and Ti Ding and Fan, {Jin Hu} and Qiao, {You Lin} and Asieh Golozar and William Wheeler and Kai Yu and Jeff Yuenger and Laurie Burdett and Chanock, {Stephen J.} and Dawsey, {Sanford M.} and Tucker, {Margaret A.} and Goldstein, {Alisa M.} and Abnet, {Christian C.} and Taylor, {Philip R.}",

note = "Funding Information: Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics; Cancer Prevention Fellowship Program, Division of Cancer Prevention, National Cancer Institute, Bethesda, USA (to P.L.H.); Health and Social Care, Northern Ireland, UK (to P.L.H.).",

year = "2013",

month = may,

doi = "10.1093/carcin/bgt030",

language = "English (US)",

volume = "34",

pages = "1062--1068",

journal = "Carcinogenesis",

issn = "0143-3334",

publisher = "Oxford University Press",

number = "5",

}

TY - JOUR

T1 - Genetic variants in sex hormone metabolic pathway genes and risk of esophageal squamous cell carcinoma

AU - Hyland, Paula L.

AU - Freedman, Neal D.

AU - Hu, Nan

AU - Tang, Ze Zhong

AU - Wang, Lemin

AU - Wang, Chaoyu

AU - Ding, Ti

AU - Fan, Jin Hu

AU - Qiao, You Lin

AU - Golozar, Asieh

AU - Wheeler, William

AU - Yu, Kai

AU - Yuenger, Jeff

AU - Burdett, Laurie

AU - Chanock, Stephen J.

AU - Dawsey, Sanford M.

AU - Tucker, Margaret A.

AU - Goldstein, Alisa M.

AU - Abnet, Christian C.

AU - Taylor, Philip R.

N1 - Funding Information: Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics; Cancer Prevention Fellowship Program, Division of Cancer Prevention, National Cancer Institute, Bethesda, USA (to P.L.H.); Health and Social Care, Northern Ireland, UK (to P.L.H.).

PY - 2013/5

Y1 - 2013/5

N2 - In China, esophageal cancer is the fourth leading cause of cancer death where essentially all cases are histologically esophageal squamous cell carcinoma (ESCC), in contrast to esophageal ade-nocarcinoma in the West. Globally, ESCC is 2.4 times more common among men than women and recently it has been suggested that sex hormones may be associated with the risk of ESCC. We examined the association between genetic variants in sex hormone metabolic genes and ESCC risk in a population from north central China with high-incidence rates. A total of 1026 ESCC cases and 1452 controls were genotyped for 797 unique tag sin-gle-nucleotide polymorphisms (SNPs) in 51 sex hormone metabolic genes. SNP-, gene- and pathway-based associations with ESCC risk were evaluated using unconditional logistic regression adjusted for age, sex and geographical location and the adaptive rank truncated product (ARTP) method. Statistical significance was determined through use of permutation for pathway- and gene-based associations. No associations were observed for the overall sex hormone metabolic pathway (P = 0.14) or subpath-ways (androgen synthesis: P = 0.30, estrogen synthesis: P = 0.15 and estrogen removal: P = 0.19) with risk of ESCC. However, six individual genes (including SULT2B1, CYP1B1, CYP3A7, CYP3A5, SHBG and CYP11A1) were significantly associated with ESCC risk (P < 0.05). Our examination of genetic variation in the sex hormone metabolic pathway is consistent with a potential association with risk of ESCC. These positive findings warrant further evaluation in relation to ESCC risk and replication in other populations.

AB - In China, esophageal cancer is the fourth leading cause of cancer death where essentially all cases are histologically esophageal squamous cell carcinoma (ESCC), in contrast to esophageal ade-nocarcinoma in the West. Globally, ESCC is 2.4 times more common among men than women and recently it has been suggested that sex hormones may be associated with the risk of ESCC. We examined the association between genetic variants in sex hormone metabolic genes and ESCC risk in a population from north central China with high-incidence rates. A total of 1026 ESCC cases and 1452 controls were genotyped for 797 unique tag sin-gle-nucleotide polymorphisms (SNPs) in 51 sex hormone metabolic genes. SNP-, gene- and pathway-based associations with ESCC risk were evaluated using unconditional logistic regression adjusted for age, sex and geographical location and the adaptive rank truncated product (ARTP) method. Statistical significance was determined through use of permutation for pathway- and gene-based associations. No associations were observed for the overall sex hormone metabolic pathway (P = 0.14) or subpath-ways (androgen synthesis: P = 0.30, estrogen synthesis: P = 0.15 and estrogen removal: P = 0.19) with risk of ESCC. However, six individual genes (including SULT2B1, CYP1B1, CYP3A7, CYP3A5, SHBG and CYP11A1) were significantly associated with ESCC risk (P < 0.05). Our examination of genetic variation in the sex hormone metabolic pathway is consistent with a potential association with risk of ESCC. These positive findings warrant further evaluation in relation to ESCC risk and replication in other populations.

UR - http://www.scopus.com/inward/record.url?scp=84877101042&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84877101042&partnerID=8YFLogxK

U2 - 10.1093/carcin/bgt030

DO - 10.1093/carcin/bgt030

M3 - Article

C2 - 23358850

AN - SCOPUS:84877101042

SN - 0143-3334

VL - 34

SP - 1062

EP - 1068

JO - Carcinogenesis

JF - Carcinogenesis

IS - 5

ER -

Genetic variants in sex hormone metabolic pathway genes and risk of esophageal squamous cell carcinoma

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this