Polymorphisms in Steroid Hormone Biosynthesis Genes and Risk of Breast Cancer and Fibrocystic Breast Conditions in Chinese Women

Abstract

Common variants in genes encoding for key enzymes involved in steroidogenesis may alter sex steroid hormone levels, thereby influencing susceptibility to breast carcinoma and related conditions. In a casecontrol study of Chinese women, we examined genotypes of the CYP11A1 pentanucleotide [(TAAAA) n ] repeat (D15S520), CYP17A1 rs743572, and HSD17B1 rs605059 polymorphisms in relation to the risk of breast cancer and fibrocystic breast conditions, comparing 615 women with breast cancer and 467 women with fibrocystic breast conditions separately with 879 women without clinical breast disease. We also evaluated whether these relationships differed by the presence of proliferation in the extratumoral epithelium or fibrocystic lesions, menopausal status, or body mass index. Only CYP11A1 genotype was related to breast cancer risk, with women homozygous for the 4-repeat allele, relative to those homozygous for the 6-repeat allele, at reduced risk (age-adjusted odds ratio, 0.58; 95% confidence interval, 0.37-0.91). There was some suggestion of a stronger inverse association for breast cancer with evidence of proliferation in the extratumoral epithelium than for breast cancer without extratumoral proliferation. Breast cancer risk associated with CYP11A1 genotype did not differ by menopausal status or body mass index level. No associations between CYP11A1, CYP17A1, and HSD17B1 genotypes and risk of fibrocystic breast conditions were observed. Our findings support the possibility that common allelic variation at the CYP11A1 D15S520 locus alters breast cancer risk in Chinese women. (Cancer Epidemiol Biomarkers Prev 2008;17(5):1066 -73)

The association between HSD17B1 Ser312Gly polymorphism and breast cancer risk: a meta-analysis including 31,053 subjects

“…First, 11 publications were collected by searching the databases [6][7][8][9][10][11][12][13][14][15][16]. Second, one study [8] included a portion of the previously published data from the Harvard Nurse's Health Study [15] and the Hawaii-Los Angeles Multiethnic Cohort [16].…”

“…Therefore, HSD17B1, which encodes the 17HSD type 1 enzyme that catalyzes the final step of estradiol biosynthesis, may play a significant role in breast cancer development [16]. A common polymorphism (Ser312Gly) of HSD17B1 had been examined in relationship to breast cancer risk in 11 studies with inconclusive results [6][7][8][9][10][11][12][13][14][15][16]. Although current evidence indicated that HSD17B1 Ser312Gly polymorphism may not affect either the catalytic or the immunological properties of the enzyme [20], some studies on cancer epidemiology suggested that Ser allele may be a significantly increased risk for breast cancer [7,8,9,13].…”

“…It is conceivable that HSD17B1 Ser312Gly polymorphism may have relationship with the breast cancer risk. To date, the association between HSD17B1 Ser312Gly polymorphism and breast cancer risk has been discussed in many published studies [6][7][8][9][10][11][12][13][14][15][16]. However, results were rather inconsistent.…”

CYP11A1 microsatellite (tttta)n polymorphism in PCOS women from South India

“…Studies from Caucasian and Asian population reported an association of 4 and 6 repeat alleles correspondingly with that of PCOS [18]. Further, (tttta) 6 allele was shown to be linked with breast cancer and prostate cancer in Chinese and Slovanian population respectively [9,25]. Daneshmand et al, (2002) observed an over-representation of 9 repeat allele in PCOS patients.…”

17Beta-hydroxysteroid dehydrogenase enzymes and breast cancer

“…Despite the importance of 17HSD1 in breast cancer, few epidemiologic studies concerning HSD17B1 and breast cancer have been conducted [21][22][23][24][25]. The largest study was reported by Feigelson et al [25] that investigated 5370 breast cancer cases and 7480 matched normal controls.…”