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Three founder mutations in BRCA1 and BRCA2 contribute to the risk of hereditary breast and ovarian cancer in Ashkenazi Jews (AJ). They are observed at increased frequency in the AJ compared to other BRCA mutations in Caucasian non-Jews (CNJ). Several authors have proposed that elevated allele frequencies in the surrounding genomic regions reflect adaptive or balancing selection. Such proposals pre
BACKGROUND: Women with a breast cancer susceptibility gene 1 (BRCA1) or breast cancer susceptibility gene 2 (BRCA2) mutation are at increased risk for developing breast and ovarian cancer. Various reproductive and hormonal factors have been shown to modify the risk of breast cancer. These studies suggest that estrogen exposure and deprivation are important in the etiology of hereditary cancer. Man
BACKGROUND: Epidemiologic studies of associations between folate intake and breast cancer are inconclusive, but folate and other plant food nutrients appear protective in women at elevated risk.OBJECTIVE: The objective was to examine the association between folate intake and the incidence of postmenopausal breast cancer.DESIGN: This prospective study included all women aged >or=50 y (n = 11699) fr
A unifying hypothesis is presented about tumour biology in hereditary breast cancer in relation to the epithelial origin and the degree of differentiation of the normal epithelium at the time of tumour initiation. By using different breast cancer syndromes as examples, it is possible to, at least partly, predict the tumour biology, clinical presentation and therapeutic response.
The overall tumour incidence and breast cancer incidence related to hormone replacement therapy (HRT) were followed in a population-based cohort of 29 508 women, aged 25-65 when interviewed in 1990-92. By the end of the follow up in December 1999, there were 226 611 person-years of observation. A total of 1145 malignant tumours were recorded (expected 1166.6; SIR = 0.98, 95% CI 0.93-1.04). There w
A hypothesis is presented suggesting that initiation of breast epithelial cell freezes the cell at least partly according to the development/differention of cell at the time of initiation. Tumour biology will mimic the physiology of normal cell development at the time of initiation and this is preserved at least partly onwards. Also preferentially, tumours will develop from the cell type that is p
A cohort of offspring of mothers with breast or ovarian cancer diagnosed in 1958-1993 was established using Swedish population-based registers. The children (n = 158,041) were born between 1941 and 1993, and their cancer incidence was followed between 1961 and 1993. A total of 3,257 tumors in 3,102 children were found. Observed numbers of cases were compared with expected numbers based on national
BACKGROUND: Colorectal carcinoma is one of the most common malignancies in the Western population, and a considerable proportion of colorectal carcinomas are estimated to have a familial background.METHODS: Individuals whose mothers were diagnosed with colon carcinoma or rectal carcinoma from 1958 to 1993, a total of 1. 48 million person-years, constituted the cohort of this Swedish population-bas
Hereditary nonpolyposis colorectal cancer (HNPCC) is caused by a germline mutation in one of several DNA repair genes, which in the tumors is reflected as microsatellite instability (MSI). MSI+ tumors have been found to carry somatic frameshift mutations in mononucleotide repeats within the coding regions of several genes involved in growth control, apoptosis, and DNA repair, e.g., TGFBRII, BAX, I
BACKGROUND: : Inherited mutations in the CDKN2A tumor suppressor gene, which encodes the p16(INK4a) protein, and in the cyclin-dependent kinase 4 (CDK4) gene confer susceptibility to cutaneous malignant melanoma. We analyzed families with two or more cases of melanoma for germline mutations in CDKN2A and CDK4 to elucidate the contribution of these gene defects to familial malignant melanoma and to
In a new population-based, matched, case-control study from southern Sweden of 571 patients with a first diagnosis of cutaneous malignant melanoma, between 1995 and 1997, and 913 healthy controls aged 16 to 80 years, the association between sunscreen use and malignant melanoma was evaluated. The median sun protection factor (SPF) used by both cases and controls was 6, range 2 to 25. Sunscreen user
In a population-based, matched, case-control study from southern Sweden of 571 patients with a first diagnosis of cutaneous malignant melanoma and 913 healthy controls aged 16-80 years, the association between sunbed use and malignant melanoma was evaluated. A total of 250 (44%) cases and 372 (41%) controls reported ever having used sunbeds. A significantly elevated odds ratio for developing malig
Approximately 5-10% of prostate cancer cases are caused by dominantly inherited susceptibility to the disease. Although advances have been made in research concerning the genetic mechanisms of hereditary prostate cancer, little is known about the psychological consequences for men at high risk of developing the disease. The aims of the present study were to examine risk perception, interest in gen
The length of the polymorphic CAG repeat in the N-terminal of the androgen receptor (AR) gene is inversely correlated with the transactivation function of the AR. Some studies have indicated that short CAG repeats are related to higher risk of prostate cancer. We performed a case-control study to investigate relations between CAG repeat length and prostate cancer risk, tumour grade, tumour stage,
The objectives of this study were to investigate the effect of family history on prostate cancer risk, to estimate the incidence of hereditary prostate cancer in southern Sweden and to assess the reliability of self-reported family history of prostate cancer. The study included consecutive prostate cancer patients and age-matched control subjects from a geographically defined population. The contr
BACKGROUND: Carriers of germline mutations in the BRCA2 gene are known to be at high risk of breast and ovarian cancers, but the risks of other cancers in mutation carriers are uncertain. We investigated these risks in 173 breast-ovarian cancer families with BRCA2 mutations identified at 20 centers in Europe and North America.METHODS: Other cancer occurrence was determined in a final cohort of 372
In this population-based, case-control study from Sweden using data collected from 1988 to 1990, an increased risk of melanoma was associated with the number of sunburns, propensity to freckle, the number of raised naevi and a family history of melanoma. Furthermore, a decreased risk was associated with occupational sun exposure. The purpose of this study was to investigate whether different histo
