The HRAS1 minisatellite locus and risk of ovarian cancer

• Published in: Cancer research (Chicago, Ill.) Ill.), 2000-01, Vol.60 (2), p.259-261
• Main Authors: WEITZEL, J. N, SHAOFENG DING, LARSON, G. P, NELSON, R. A, GOODMAN, A, GRENDYS, E. C, BALL, H. G, KRONTIRIS, T. G
• Format: Article
• Language: English
• Subjects: Alleles; Biological and medical sciences; BRCA1 gene; Case-Control Studies; chromosome 11; Chromosome Mapping; Chromosomes, Human, Pair 11; European Continental Ancestry Group - genetics; Female; Female genital diseases; Genes, BRCA1; Genes, ras; Gynecology. Andrology. Obstetrics; Heterozygote; HRAS1 gene; Humans; Medical sciences; Middle Aged; Minisatellite Repeats; Minisatellites; Neoplasm Staging; Ovarian Neoplasms - epidemiology; Ovarian Neoplasms - genetics; Ovarian Neoplasms - pathology; Reference Values; Risk Factors; Tumors; United States
• ISSN: 0008-5472; 1538-7445

Approximately 10% of ovarian cancers are due to mutations in highly penetrant inherited cancer susceptibility genes. The highly polymorphic HRAS1 minisatellite locus, located just downstream from the proto-oncogene H-ras-1 on chromosome 11p, consists of four common progenitor alleles and several dozen rare alleles, which apparently derive from mutations of the progenitors. Mutant alleles of this locus represent a major risk factor for cancers of the breast, colorectum, and bladder, and it was found that BRCAI mutation carriers with at least one rare HRAS1 allele have a greater risk of ovarian cancer than BRCA1 carriers with only common HRAS1 alleles. There are no conclusive studies of HRAS1 alleles in sporadic epithelial ovarian cancer. A case-control study of HRAS1 alleles was performed on DNA from 136 Caucasian patients with ovarian cancer and 108 cancer-free controls using conventional (Southern blot) and PCR-based methods to determine the frequency of rare HRAS1 alleles. Odds ratios (ORs) were estimated using unconditional logistic regression methods. A single degree of freedom test was used to assess the significance of linear trend across categories of increasing exposure. A statistically significant association between rare HRAS1 alleles and risk of ovarian cancer was observed [OR, 1.70; 95% confidence interval (CI), 1.03-2.80; P = 0.04]. Having only one rare allele was associated with a relative risk of 1.66 (95% CI, 0.91-3.01), whereas having two rare alleles increased the relative risk to 2.86 (95% CI, 0.75-10.94; trend P = 0.03). Analysis of HRAS1 allele types by the age of the case at diagnosis revealed that younger cases ( or = 0 years; OR, 1.89; 95% CI, 0.90-3.98; P = 0.09). Rare HRAS1 alleles contribute to ovarian cancer predisposition in the general population. Thus, the HRAS1-variable number of tandem repeats locus may function as a modifier of ovarian cancer risk in both sporadic and hereditary ovarian cancer.