The HRAS1 minisatellite locus and risk of ovarian cancer
Department of Obstetrics and Gynecology
Alleles; Case-Control Studies; Chromosome Mapping; *Chromosomes, Human, Pair 11; European Continental Ancestry Group; Female; Genes, BRCA1; *Genes, ras; Heterozygote; Humans; Middle Aged; *Minisatellite Repeats; Neoplasm Staging; Ovarian Neoplasms; Reference Values; Risk Factors; United States
Obstetrics and Gynecology
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 (<45 >years) had a borderline statistically significant increased association with rare HRAS1 alleles compared to older 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.
Cancer Res. 2000 Jan 15;60(2):259-61.
Weitzel JN, Ding S, Larson GP, Nelson RA, Goodman A, Grendys EC, Ball HG, Krontiris TG. (2000). The HRAS1 minisatellite locus and risk of ovarian cancer. Obstetrics and Gynecology Publications. Retrieved from https://escholarship.umassmed.edu/obgyn_pp/47