Journal Article

Single nucleotide polymorphisms of follicle-stimulating hormone receptor are associated with ovarian cancer susceptibility

C.Q. Yang, K.Y.K. Chan, H.Y.S. Ngan, U.S. Khoo, P.M. Chiu, Q.K.Y. Chan, W.C. Xue and A.N.Y. Cheung

in Carcinogenesis

Volume 27, issue 7, pages 1502-1506
Published in print July 2006 | ISSN: 0143-3334
Published online March 2006 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgl014
Single nucleotide polymorphisms of follicle-stimulating hormone receptor are associated with ovarian cancer susceptibility

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Epidemiological studies suggested that ovulation was associated with ovarian carcinogenesis. Follicle-stimulating hormone (FSH) played an important role in follicular development and was recently found to affect growth of ovarian epithelial cells. Single nucleotide polymorphisms (SNPs) Thr307Ala and Asn680Ser were two non-synonymous variations in the coding region of the FSH receptor (FSHR) gene. This hitherto first case–control study investigating the association between these two FSHR SNPs and the risk of ovarian cancer involved 202 histopathologically confirmed ovarian cancer patients and 266 age-matched cancer-free control subjects using restriction fragment length polymorphism assay and direct sequencing. Our results demonstrated that the 307Ala and 680Ser carriers were associated with significantly increased risk of developing serous and mucinous types of ovarian cancers (P < 0.0005, OR = 2.60, 95% CI = 1.56–4.34; and P < 0.0005, OR = 2.89, 95% CI = 1.73–4.84, adjusted for age, respectively) but not endometrioid and clear cell types. The two SNPs were found to be in modest linkage disequilibrium, D′ = 0.804 and 0.701, r2 = 0.581 and 0.406 for the cancer and control groups, respectively. The major haplotype of 307Ala-680Ser was also associated with higher cancer risk (P = 0.033, OR = 1.39, 95% CI = 1.03–1.88), especially for the serous and mucinous carcinomas (P = 0.001, OR = 1.82, 95% CI = 1.27–2.60). Our results suggested that the two FSHR SNPs might affect the susceptibility of women to specific subtypes of ovarian cancer. Different types of ovarian cancer might adopt distinct carcinogenetic pathways. Such understanding may be important in selecting patients for ovulation induction therapy.

Keywords: FSH, follicle-stimulating hormone; SNP, single nucleotide polymorphism; FSHR, FSH receptor; SC, serous carcinoma; MC, mucinous carcinoma; EC, endometrioid carcinoma; CC, clear cell carcinoma

Journal Article.  3897 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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