Genetic Susceptibility Factors on Genes Involved in the Steroid Hormone Biosynthesis Pathway and Progesterone Receptor for Gastric Cancer Risk

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2012 Oct 31

PMID 23110082

Citations 12

Authors

Lisa Y Cho

Jae Jeong Yang

Kwang-Pil Ko

Seung Hyun Ma

Aesun Shin

Bo Youl Choi

Dong Soo Han

Kyu Sang Song

Yong Sung Kim

Soung-Hoon Chang

Hai-Rim Shin

Daehee Kang

Keun-Young Yoo

Sue K Park

Affiliations

Soon will be listed here.

Abstract

Background: The objective of the study was to investigate the role of genes (HSD3B1, CYP17A1, CYP19A1, HSD17B2, HSD17B1) involved in the steroid hormone biosynthesis pathway and progesterone receptor (PGR) in the etiology of gastric cancer in a population-based two-phase genetic association study.

Methods: In the discovery phase, 108 candidate SNPs in the steroid hormone biosynthesis pathway related genes and PGR were analyzed in 76 gastric cancer cases and 322 controls in the Korean Multi-Center Cancer Cohort. Statistically significant SNPs identified in the discovery phase were re-evaluated in an extended set of 386 cases and 348 controls. Pooled- and meta-analyses were conducted to summarize the results.

Results: Of the 108 SNPs in steroid hormone biosynthesis pathway related genes and PGR analyzed in the discovery phase, 23 SNPs in PGR in the recessive model and 10 SNPs in CYP19A1 in the recessive or additive models were significantly associated with increased gastric cancer risk (p<0.05). The minor allele frequencies of the SNPs in both the discovery and extension phases were not statistically different. Pooled- and meta-analyses showed CYP19A1 rs1004982, rs16964228, and rs1902580 had an increased risk for gastric cancer (pooled OR [95% CI] = 1.22 [1.01-1.48], 1.31 [1.03-1.66], 3.03 [1.12-8.18], respectively). In contrast, all PGR SNPs were not statistically significantly associated with gastric cancer risk.

Conclusions: Our findings suggest CYP19A1 that codes aromatase may play an important role in the association of gastric cancer risk and be a genetic marker for gastric cancer susceptibility.

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References

Heuch I, Kvale G . Does breastfeeding affect the risk of gastric cancer?. Int J Cancer. 2003; 106(6):982-3. DOI: 10.1002/ijc.11291. View

Irahara N, Miyoshi Y, Taguchi T, Tamaki Y, Noguchi S . Quantitative analysis of aromatase, sulfatase and 17beta-HSD(1) mRNA expression in soft tissue metastases of breast cancer. Cancer Lett. 2006; 243(1):23-31. DOI: 10.1016/j.canlet.2005.11.010. View

Al Sarakbi W, Mokbel R, Salhab M, Jiang W, Reed M, Mokbel K . The role of STS and OATP-B mRNA expression in predicting the clinical outcome in human breast cancer. Anticancer Res. 2007; 26(6C):4985-90. View

Harada N, Utsumi T, Takagi Y . Tissue-specific expression of the human aromatase cytochrome P-450 gene by alternative use of multiple exons 1 and promoters, and switching of tissue-specific exons 1 in carcinogenesis. Proc Natl Acad Sci U S A. 1993; 90(23):11312-6. PMC: 47972. DOI: 10.1073/pnas.90.23.11312. View

Heuch I, Kvale G . Menstrual and reproductive factors and risk of gastric cancer: a Norwegian cohort study. Cancer Causes Control. 2000; 11(9):869-74. DOI: 10.1023/a:1008975817061. View

Mahendroo M, Means G, Mendelson C, Simpson E . Tissue-specific expression of human P-450AROM. The promoter responsible for expression in adipose tissue is different from that utilized in placenta. J Biol Chem. 1991; 266(17):11276-81. View

Cai H, Shu X, Egan K, Cai Q, Long J, Gao Y . Association of genetic polymorphisms in CYP19A1 and blood levels of sex hormones among postmenopausal Chinese women. Pharmacogenet Genomics. 2008; 18(8):657-64. PMC: 2613759. DOI: 10.1097/FPC.0b013e3282fe3326. View

Hardy R, Thompson S . Detecting and describing heterogeneity in meta-analysis. Stat Med. 1998; 17(8):841-56. DOI: 10.1002/(sici)1097-0258(19980430)17:8<841::aid-sim781>3.0.co;2-d. View

Izawa M, Inoue M, Osaki M, Ito H, Harada T, Terakawa N . Cytochrome P450 aromatase gene (CYP19) expression in gastric cancer. Gastric Cancer. 2008; 11(2):103-10. DOI: 10.1007/s10120-008-0463-x. View

10.

Goodman M, Lurie G, Thompson P, McDuffie K, Carney M . Association of two common single-nucleotide polymorphisms in the CYP19A1 locus and ovarian cancer risk. Endocr Relat Cancer. 2008; 15(4):1055-60. PMC: 2663409. DOI: 10.1677/ERC-08-0104. View

11.

Lindblad M, Garcia Rodriguez L, Chandanos E, Lagergren J . Hormone replacement therapy and risks of oesophageal and gastric adenocarcinomas. Br J Cancer. 2006; 94(1):136-41. PMC: 2361087. DOI: 10.1038/sj.bjc.6602906. View

12.

Wu C, Chang H, Kao H, Lui W, Peng F, Chi C . The nontransformed progesterone and estrogen receptors in gastric cancer. Gastroenterology. 1992; 102(5):1639-46. DOI: 10.1016/0016-5085(92)91724-i. View

13.

Canzian F, Cox D, Setiawan V, Stram D, Ziegler R, Dossus L . Comprehensive analysis of common genetic variation in 61 genes related to steroid hormone and insulin-like growth factor-I metabolism and breast cancer risk in the NCI breast and prostate cancer cohort consortium. Hum Mol Genet. 2010; 19(19):3873-84. PMC: 2935856. DOI: 10.1093/hmg/ddq291. View

14.

Brodie A, Lu Q, Nakamura J . Aromatase in the normal breast and breast cancer. J Steroid Biochem Mol Biol. 1997; 61(3-6):281-6. View

15.

Ohtani M, Garcia A, Rogers A, Ge Z, Taylor N, Xu S . Protective role of 17 beta -estradiol against the development of Helicobacter pylori-induced gastric cancer in INS-GAS mice. Carcinogenesis. 2007; 28(12):2597-604. DOI: 10.1093/carcin/bgm150. View

16.

Pricci M, Linsalata M, Russo F, Messa C, Amati L, Caradonna L . Effects of 17beta-estradiol administration on apoptosis and polyamine content in AGS cell line. Anticancer Res. 2002; 21(5):3215-20. View

17.

Ma X, Qi X, Chen C, Lin H, Xiong H, Li Y . Association between CYP19 polymorphisms and breast cancer risk: results from 10,592 cases and 11,720 controls. Breast Cancer Res Treat. 2010; 122(2):495-501. DOI: 10.1007/s10549-009-0693-6. View

18.

Kaneko S, Tamakoshi A, Ohno Y, Mizoue T, Yoshimura T . Menstrual and reproductive factors and the mortality risk of gastric cancer in Japanese menopausal females. Cancer Causes Control. 2003; 14(1):53-9. DOI: 10.1023/a:1022596104796. View

19.

Tsuchiya Y, Nakajima M, Yokoi T . Cytochrome P450-mediated metabolism of estrogens and its regulation in human. Cancer Lett. 2005; 227(2):115-24. DOI: 10.1016/j.canlet.2004.10.007. View

20.

Ashton K, Proietto A, Otton G, Symonds I, McEvoy M, Attia J . Polymorphisms in genes of the steroid hormone biosynthesis and metabolism pathways and endometrial cancer risk. Cancer Epidemiol. 2010; 34(3):328-37. DOI: 10.1016/j.canep.2010.03.005. View