Variants in hormone-related genes and the risk of biliary tract cancers and stones: A population-based study in China

Sue Kyung Park, Gabriella Andreotti, Lori C. Sakoda, Yu Tang Gao, Asif Rashid, Jinbo Chen, Bingshu E. Chen, Philip S. Rosenberg, Ming Chang Shen, Bing Sheng Wang, Tian Quan Han, Bai He Zhang, Meredith Yeager, Stephen Chanock, Ann W. Hsing

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Abstract

Biliary tract cancers, encompassing gallbladder, extrahepatic bile duct and ampulla of Vater cancers, are uncommon but often fatal malignancies. Hormone-related factors, including parity, oral contraceptive use, obesity, and gallstones, have been implicated in the etiology of these cancers. To further clarify the role of hormones in biliary tract cancers and biliary stones, we genotyped 18 single-nucleotide polymorphisms (SNPs) in nine genes involved in steroid hormone biosynthesis, metabolism and transport in a population-based case-control study in Shanghai, China. This study included subjects who completed an interview and provided blood, which totaled 411 biliary tract cancer and 893 biliary stone patients and 786 healthy Shanghai residents. The CYP1A1 IVS1 + 606 (rs2606345) T allele was associated with gallbladder [odds ratio (OR) = 2.0, 95% confidence interval (CI), 1.3-3.0] and bile duct cancers (OR = 1.8, 95% CI = 1.1-3.1), whereas the CYP1A1 Ex7 + 131 (rs1048943) G allele was associated with ampulla of Vater cancer (OR = 2.9, 95% CI = 1.5-5.4). After taking into account multiple comparisons for SNPs within each gene, CYP1A1 was significantly associated with gallbladder (P = 0.004) and ampulla of Vater cancers (P = 0.01), but borderline with bile duct cancer (P = 0.06). The effect of CYP1A1 IVS1 + 606 on gallbladder cancer was more pronounced among non-obese (body mass index < 23) (OR = 3.3, 95% CI = 1.8-6.1; P interaction = 0.001). Among women taking oral contraceptives, the effect of SHBG Ex8 + 6 (rs6259) on gallbladder cancer (OR = 6.7, 95% CI = 2.2-20.5; P interaction = 0.001) and stones (OR = 2.3, 95% CI = 1.1-4.9; P-interaction = 0.05) was statistically significant. Our findings suggest that common variants in hormone-related genes contribute to the risk of biliary tract cancers and stones, possibly by modulating hormone metabolism.

Original languageEnglish
Pages (from-to)606-614
Number of pages9
JournalCarcinogenesis
Volume30
Issue number4
DOIs
StatePublished - 17 Apr 2009

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Biliary Tract Neoplasms
China
Cytochrome P-450 CYP1A1
Odds Ratio
Hormones
Confidence Intervals
Ampulla of Vater
Gallbladder Neoplasms
Bile Duct Neoplasms
Population
Genes
Neoplasms
Oral Contraceptives
Gallbladder
Single Nucleotide Polymorphism
Alleles
Extrahepatic Bile Ducts
Gallstones
Contraceptive Agents
Parity

Cite this

Park, Sue Kyung ; Andreotti, Gabriella ; Sakoda, Lori C. ; Gao, Yu Tang ; Rashid, Asif ; Chen, Jinbo ; Chen, Bingshu E. ; Rosenberg, Philip S. ; Shen, Ming Chang ; Wang, Bing Sheng ; Han, Tian Quan ; Zhang, Bai He ; Yeager, Meredith ; Chanock, Stephen ; Hsing, Ann W. / Variants in hormone-related genes and the risk of biliary tract cancers and stones : A population-based study in China. In: Carcinogenesis. 2009 ; Vol. 30, No. 4. pp. 606-614.
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abstract = "Biliary tract cancers, encompassing gallbladder, extrahepatic bile duct and ampulla of Vater cancers, are uncommon but often fatal malignancies. Hormone-related factors, including parity, oral contraceptive use, obesity, and gallstones, have been implicated in the etiology of these cancers. To further clarify the role of hormones in biliary tract cancers and biliary stones, we genotyped 18 single-nucleotide polymorphisms (SNPs) in nine genes involved in steroid hormone biosynthesis, metabolism and transport in a population-based case-control study in Shanghai, China. This study included subjects who completed an interview and provided blood, which totaled 411 biliary tract cancer and 893 biliary stone patients and 786 healthy Shanghai residents. The CYP1A1 IVS1 + 606 (rs2606345) T allele was associated with gallbladder [odds ratio (OR) = 2.0, 95{\%} confidence interval (CI), 1.3-3.0] and bile duct cancers (OR = 1.8, 95{\%} CI = 1.1-3.1), whereas the CYP1A1 Ex7 + 131 (rs1048943) G allele was associated with ampulla of Vater cancer (OR = 2.9, 95{\%} CI = 1.5-5.4). After taking into account multiple comparisons for SNPs within each gene, CYP1A1 was significantly associated with gallbladder (P = 0.004) and ampulla of Vater cancers (P = 0.01), but borderline with bile duct cancer (P = 0.06). The effect of CYP1A1 IVS1 + 606 on gallbladder cancer was more pronounced among non-obese (body mass index < 23) (OR = 3.3, 95{\%} CI = 1.8-6.1; P interaction = 0.001). Among women taking oral contraceptives, the effect of SHBG Ex8 + 6 (rs6259) on gallbladder cancer (OR = 6.7, 95{\%} CI = 2.2-20.5; P interaction = 0.001) and stones (OR = 2.3, 95{\%} CI = 1.1-4.9; P-interaction = 0.05) was statistically significant. Our findings suggest that common variants in hormone-related genes contribute to the risk of biliary tract cancers and stones, possibly by modulating hormone metabolism.",
author = "Park, {Sue Kyung} and Gabriella Andreotti and Sakoda, {Lori C.} and Gao, {Yu Tang} and Asif Rashid and Jinbo Chen and Chen, {Bingshu E.} and Rosenberg, {Philip S.} and Shen, {Ming Chang} and Wang, {Bing Sheng} and Han, {Tian Quan} and Zhang, {Bai He} and Meredith Yeager and Stephen Chanock and Hsing, {Ann W.}",
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Park, SK, Andreotti, G, Sakoda, LC, Gao, YT, Rashid, A, Chen, J, Chen, BE, Rosenberg, PS, Shen, MC, Wang, BS, Han, TQ, Zhang, BH, Yeager, M, Chanock, S & Hsing, AW 2009, 'Variants in hormone-related genes and the risk of biliary tract cancers and stones: A population-based study in China', Carcinogenesis, vol. 30, no. 4, pp. 606-614. https://doi.org/10.1093/carcin/bgp024

Variants in hormone-related genes and the risk of biliary tract cancers and stones : A population-based study in China. / Park, Sue Kyung; Andreotti, Gabriella; Sakoda, Lori C.; Gao, Yu Tang; Rashid, Asif; Chen, Jinbo; Chen, Bingshu E.; Rosenberg, Philip S.; Shen, Ming Chang; Wang, Bing Sheng; Han, Tian Quan; Zhang, Bai He; Yeager, Meredith; Chanock, Stephen; Hsing, Ann W.

In: Carcinogenesis, Vol. 30, No. 4, 17.04.2009, p. 606-614.

Research output: Contribution to journalArticle

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T1 - Variants in hormone-related genes and the risk of biliary tract cancers and stones

T2 - A population-based study in China

AU - Park, Sue Kyung

AU - Andreotti, Gabriella

AU - Sakoda, Lori C.

AU - Gao, Yu Tang

AU - Rashid, Asif

AU - Chen, Jinbo

AU - Chen, Bingshu E.

AU - Rosenberg, Philip S.

AU - Shen, Ming Chang

AU - Wang, Bing Sheng

AU - Han, Tian Quan

AU - Zhang, Bai He

AU - Yeager, Meredith

AU - Chanock, Stephen

AU - Hsing, Ann W.

PY - 2009/4/17

Y1 - 2009/4/17

N2 - Biliary tract cancers, encompassing gallbladder, extrahepatic bile duct and ampulla of Vater cancers, are uncommon but often fatal malignancies. Hormone-related factors, including parity, oral contraceptive use, obesity, and gallstones, have been implicated in the etiology of these cancers. To further clarify the role of hormones in biliary tract cancers and biliary stones, we genotyped 18 single-nucleotide polymorphisms (SNPs) in nine genes involved in steroid hormone biosynthesis, metabolism and transport in a population-based case-control study in Shanghai, China. This study included subjects who completed an interview and provided blood, which totaled 411 biliary tract cancer and 893 biliary stone patients and 786 healthy Shanghai residents. The CYP1A1 IVS1 + 606 (rs2606345) T allele was associated with gallbladder [odds ratio (OR) = 2.0, 95% confidence interval (CI), 1.3-3.0] and bile duct cancers (OR = 1.8, 95% CI = 1.1-3.1), whereas the CYP1A1 Ex7 + 131 (rs1048943) G allele was associated with ampulla of Vater cancer (OR = 2.9, 95% CI = 1.5-5.4). After taking into account multiple comparisons for SNPs within each gene, CYP1A1 was significantly associated with gallbladder (P = 0.004) and ampulla of Vater cancers (P = 0.01), but borderline with bile duct cancer (P = 0.06). The effect of CYP1A1 IVS1 + 606 on gallbladder cancer was more pronounced among non-obese (body mass index < 23) (OR = 3.3, 95% CI = 1.8-6.1; P interaction = 0.001). Among women taking oral contraceptives, the effect of SHBG Ex8 + 6 (rs6259) on gallbladder cancer (OR = 6.7, 95% CI = 2.2-20.5; P interaction = 0.001) and stones (OR = 2.3, 95% CI = 1.1-4.9; P-interaction = 0.05) was statistically significant. Our findings suggest that common variants in hormone-related genes contribute to the risk of biliary tract cancers and stones, possibly by modulating hormone metabolism.

AB - Biliary tract cancers, encompassing gallbladder, extrahepatic bile duct and ampulla of Vater cancers, are uncommon but often fatal malignancies. Hormone-related factors, including parity, oral contraceptive use, obesity, and gallstones, have been implicated in the etiology of these cancers. To further clarify the role of hormones in biliary tract cancers and biliary stones, we genotyped 18 single-nucleotide polymorphisms (SNPs) in nine genes involved in steroid hormone biosynthesis, metabolism and transport in a population-based case-control study in Shanghai, China. This study included subjects who completed an interview and provided blood, which totaled 411 biliary tract cancer and 893 biliary stone patients and 786 healthy Shanghai residents. The CYP1A1 IVS1 + 606 (rs2606345) T allele was associated with gallbladder [odds ratio (OR) = 2.0, 95% confidence interval (CI), 1.3-3.0] and bile duct cancers (OR = 1.8, 95% CI = 1.1-3.1), whereas the CYP1A1 Ex7 + 131 (rs1048943) G allele was associated with ampulla of Vater cancer (OR = 2.9, 95% CI = 1.5-5.4). After taking into account multiple comparisons for SNPs within each gene, CYP1A1 was significantly associated with gallbladder (P = 0.004) and ampulla of Vater cancers (P = 0.01), but borderline with bile duct cancer (P = 0.06). The effect of CYP1A1 IVS1 + 606 on gallbladder cancer was more pronounced among non-obese (body mass index < 23) (OR = 3.3, 95% CI = 1.8-6.1; P interaction = 0.001). Among women taking oral contraceptives, the effect of SHBG Ex8 + 6 (rs6259) on gallbladder cancer (OR = 6.7, 95% CI = 2.2-20.5; P interaction = 0.001) and stones (OR = 2.3, 95% CI = 1.1-4.9; P-interaction = 0.05) was statistically significant. Our findings suggest that common variants in hormone-related genes contribute to the risk of biliary tract cancers and stones, possibly by modulating hormone metabolism.

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