title: Hemochromatosis gene mutations among Finnish male breast and prostate cancer patients.
abstract: Hereditary hemochromatosis (HH), the most common genetic disease in northern Europeans, is an autosomal recessive disorder of iron metabolism. The association between hepatocellular carcinoma and HFE homozygosity is well documented, but recently HFE hetero- and homozygosity has also been linked to nonhepatocellular malignancies, including female breast cancer. We hypothesized that C282Y and H63D mutations in the HFE gene could contribute to male breast cancer (MBC) and prostate cancer (PC) susceptibility at the population level in Finland. We screened the 2 major HFE mutations, H63D and C282Y, from 116 MBC cases diagnosed in Finland between 1967 and 1996, 843 consecutive unselected PC cases diagnosed at the Pirkanmaa Hospital District between 1999 and 2001 and 480 anonymous blood donor controls by minisequencing. Our results indicate that the frequencies of the HFE mutations do not significantly differ between MBC and PC patients and the population-based controls. No significantly altered risks for MBC or PC among carriers of the 2 variants were observed. However, HFE mutations were seen twice as often among carriers of a common BRCA2 mutation 9346(-2)A-->G compared with the rest of the MBC cases, indicating that HFE may be an MBC risk modifier gene among BRCA2 mutation carriers. In conclusion, our results indicate a minor role for the HFE mutations C282Y and H63D in the causation of MBC and PC, but carriers of both BRCA2 9346(-2)A-->G and an HFE mutation may be at an increased risk.
authors: Laboratory of Cancer Genetics, Institute of Medical Technology, University of Tampereand Tampere University Hospital, Tampere, Finland.
authors: Kirsi
authors: K
authors: Syrjäkoski
authors: Henna
authors: H
authors: Fredriksson
authors: Tarja
authors: T
authors: Ikonen
authors: Tuula
authors: T
authors: Kuukasjärvi
authors: Ville
authors: V
authors: Autio
authors: Mika P
authors: MP
authors: Matikainen
authors: Teuvo L J
authors: TL
authors: Tammela
authors: Pasi A
authors: PA
authors: Koivisto
authors: Johanna
authors: J
authors: Schleutker
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018567:Breast Neoplasms, Male / Q000235:genetics*; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D005260:Female; D005387:Finland; D020022:Genetic Predisposition to Disease; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000235:genetics*; D012307:Risk Factors
chemical_list: C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins