CYPJ7 Genotype and Breast Cancer Risk1

The MspAI polymorphism in the 5’ untranslated region of CYPJ 7 has been evaluated as a breast cancer risk factor in a hospital-based case-control study in New York City. The study population consisted of 363 women [123 breast cancer patients and 240 patient controls (123 benign breast disease without atypical hyperplasia, 117 women without breast disease)]. There were 224 Caucasians (76 cases, 148 controls), 55 African-Americans (20 cases, 35 controls) and 84 Hispanics (27 cases, 57 controls); 142 premenopausal women and 221 postmenopausal women. Consistent with a previous report (Feigelson et aL, Cancer Res., 57: 1063-1065, 1997) we found no evidence to implicate the minor variant (restriction site present allele, designated A2) as a breast cancer risk factor. Furthermore, we sought evidence to implicate the minor variant of CYPJ7 in the development of more aggressive breast cancers (n = 38/121) as had been reported previously. Although confidence intervals (CI) overlap, the data presented here do not provide support for previously reported findings (odds ratio, 0.9; 95% CI, 0.4-2.0; n = 38 versus odds ratio, 2.5; 95% CI, 1.1-5.2; n = 40). Clearly this question needs to be resolved in a larger study. No evidence was found to support the contention that inheritance of the minor variant is a predictor of early age at menarche. Allelic frequencies between different ethnic groups were not found to be different with the exception of Hispanic controls, in which the genotypic distribution was not consistent with the Hardy-Weinberg equilibrium. Introduction Epidemiological studies have provided a plausible basis for an association between breast cancer risk and steroid/estrogen or xenoestrogen exposure ( 1 , 2). A recent report (3) further considered the possibility that a common polymorphism in CYPJ 7, a 17a-steroid hydroxylase and 17/20-lyase, is a determinant of human breast cancer risk. The minor variant (A2) differs from Received 12/9/97: revised 6/29/98: accepted 7/14/98. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. I This work was supported by NIH Grant U0I CA 62591. 2 To whom requests for reprints should be addressed, at NIOSH-CDC, MS 3014, HELD TMBB, 1095 Willowdale Road, Morgantown, WV 26505-2888. Phone: (304) 285-622 1 : E-mail: [email protected]. the major variant (Al) by one nucleotide in the 5’ untranslated region (T -sC at position 193 1 , Ref. 4). It was reasoned that the C-allele may have enhanced transcriptional activity because of the creation of an Sp-l-type promotor motif. Further, because CYPJ7 has a fundamental role in steroid metabolism, it was further reasoned that this allele may be associated with increased breast cancer risk. In that study, three ethnic groups were analyzed: African-Americans, Latinos, and Asians. Because the genotypic distributions were similar in each ethnic group (--35:50:15), data were combined for analysis (3). It was reported that the A2 allele was over-represented in women with a diagnosis of advanced breast cancer (Al homozygotes versus A2 homozygotes and heterozygotes: OR,3 2.5; 95% CI, 1.15.9). Furthermore, it was observed that among controls, Al homozygotes were likely to have later age at menarche. In this study, we report the results of a hospital-based case-control study of breast cancer in which the CYPJ7 genotypes of the participants have been determined. The current study focuses on Caucasians, African-Americans, and Latinos recruited in New York City. Materials and Methods Human Samples. The design and recruitment of the breast cancer case-control study has been described previously (4). Briefly, women were enrolled at the Mount Sinai Medical Center (New York) between September 1994 and February 1996. All of the cases were approached before, or within 2 months after, diagnostic biopsy. The participation rate (64.5%) was comparable in cases and controls and among ethnic groups. Samples were frequency-matched on age, race, and diagnosis: and genotypes were determined for 363 women. The case group was matched to each of two separate control groups (benign breast disease without atypia and women without breast disease). Ethnicity was self-described, and the study included 224 Caucasians (76 cases, 148 controls), 55 African-Americans (20 cases, 35 controls), and 84 Hispanics (27 cases, 57 controls). Menstrual history was determined by questionnaire. For 121 breast cancer cases in which full histopathology was available, classification of tumors as aggressive or nonaggressive was possible. Women presenting with stage-3 or -4 disease and who had undergone chemotherapy without lymph node dissection were considered to have aggressive tumors. Infiltrating carcinomas with lymph node involvement or lymphatic invasion were also designated as aggressive. Small invasive carcinomas with favorable histology and ductal carcinoma i i situ (in which lymph nodes were not dissected) were regarded as nonaggressive. CYPJ7 Genotype. CYP17 genotype was determined exactly as described (3). However, several technical discrepancies should be noted. The original report describing this polymorphism and on June 22, 2017. © 1998 American Association for Cancer Research. cebp.aacrjournals.org Downloaded from