Guðríður Ólafsdóttir

Linkage to BRCA2 region in hereditary male breast cancer

Breast cancer is rare in men, and family history of the disease is a risk factor. The recently discovered BRCA2 gene on chromosome 13q is thought to account for some families with increased risk of breast cancer, including male breast cancer. We describe a family with multiple cases of male breast cancer but, interestingly, no increase in female breast cancer. Linkage to the BRCA2 region is demonstrated and all the affected men share the same haplotype for the BCRA2 markers and loss of the other alleles in their tumours.

The effect of a single BRCA2 mutation on cancer in Iceland.

Objective: To estimate the risk of malignant diseases in families of probands with the same mutation in the BRCA2 gene. Design: A cohort study using record linkage of a breast cancer family resource and the Icelandic Cancer Registry. Setting: Iceland. Subjects: Families of 995 breast cancer patients, from which 887 were tested for a single founder 999del5 mutation; 90 had the mutation and 797 did not. Results: Relatives of probands with the mutation had significantly increased relative risk (RR) of breast cancer. For first degree relatives, the RR was 7.55 (95% CI 6.04 to 9.03) but was 1.72 (95% CI 1.49 to 1.96) in first degree relatives of probands without the mutation. For prostate and ovarian cancer, the first and second degree relatives of probands with the mutation had a significantly increased RR, but in families of probands without the mutation no significant familial risk was found. Conclusions: The 999del5 mutation in the BRCA2 gene explains a substantial proportion of familial risk of breast cancer in Iceland, but significant familial risk remains in relatives of probands without the mutation. For prostate and ovarian cancer, the mutation accounts for most of the familiality observed in families of breast cancer patients.

Neoplastic diseases in families of breast cancer patients.

OBJECTIVE--To investigate whether the risk of cancer at all sites, and at individual sites other than breast, prostate, ovaries, and endometrium, is increased among relatives of breast cancer patients compared with the general population. DESIGN--A cohort of family members of breast cancer patients was established. The probands were chosen by year of birth or time of diagnosis. Any influence of knowledge of the cancer experience of the relatives has been avoided. The risk estimates are based on expected numbers computed from age and time specific incidence rates for the Icelandic population. SETTING--Iceland. SUBJECTS--The population of Iceland. MAIN OUTCOME MEASURES--Relative risks by degree of relatedness and age of proband. RESULTS--The relative risk of cancer at all sites is raised for males and females. This is more than expected based on the known familial risk of breast cancer, prostate, and ovarian cancer. The excess risk of breast, prostate, and ovarian cancer is confirmed, but not that of cancer of the endometrium. The risk of cancer of the pancreas in both sexes and the stomach and kidneys in females is significantly raised. No evidence was found for decreased risk for any cancer type. CONCLUSIONS--The risk of cancer at all sites in relatives of breast cancer patients is increased. In addition to the risk of breast, prostate, and ovarian cancer, the risk of pancreas cancer and cancer of the stomach and kidneys in females is raised, but the last mentioned observations need further confirmation.

Papillary Thyroid Carcinoma in Iceland: A study of the Occurrence in families and the coexistence of other primary tumours

This paper presents evidence from Iceland which indicates that papillary thyroid carcinoma occurs in certain families more often than expected. Thyroid carcinoma was also seen to coexist with some other cancer types more often than expected. We studied all families (n = 373) with papillary thyroid carcinoma diagnosed between 1955 and 1984 in Iceland. Familial papillary carcinoma occurred in 3.8% of these families. This frequency was higher than expected but not significantly increased. Second primaries in women, and especially the incidence of kidney and breast cancer, were significantly increased. Cancer of the kidney and CNS tumours were significantly increased in propositi when both sexes were taken together. No increase in the incidence of other malignancies was observed in first degree relatives of patients with papillary thyroid carcinoma.

A case-control study to estimate the impact of the Icelandic population-based mammography screening program on breast cancer death.

Background: The Icelandic breast cancer screening program, initiated November 1987 in Reykjavik and covering the whole country from December 1989, comprises biennial invitation to mammography for women aged 40–69 years old. Purpose: To estimate the impact of mammography service screening in Iceland on deaths from breast cancer. Material and Methods: Cases were deaths from breast cancer from 1990 onwards in women aged 40 and over at diagnosis, during the period November 1987 to December 31, 2002. Age- and screening-area-matched, population-based controls were women who had also been invited to screening but were alive at the time their case died. Results: Using conditional logistic regression on the data from 226 cases and 902 controls, the odds ratio for the risk of death from breast cancer in those attending at least one screen compared to those never screened was 0.59 (95% CI 0.41–0.84). After adjustment for healthy-volunteer bias and screening-opportunity bias, the odds ratio was 0.65 (95% CI 0.39–1.09). Conclusion: These results indicate a 35–40% reduction in breast cancer deaths by attending the Icelandic breast cancer screening program. These results are consistent with the overall evidence from other observational evaluations of mammography-based programs.

Monoclonal gammopathy in Iceland: a population-based registry and follow-up.

Summary. The term monoclonal gammopathy (MG) signifies the benign or malignant clonal growth of B lymphocytes. In the present study, monoclonal gammopathy of unknown significance (MGUS) was defined as those patients with no identified haematological malignancy. A database was constructed of all 713 MG patients in Iceland between 1976 and 1997 and compared with the Icelandic Cancer Registry. The age‐standardized incidence per 100 000 of MG was 10·3 for males and 8·6 for females, calculated for the whole period, rising steadily from 5·8 (men) and 4·9 (women) during the 5‐year period 1976–80 to 14·7 (men) and 12·5 (women) during the last 5 year period. Age‐standardized incidence rates were very low for subjects under 50 years of age, then increased with age from 11 and 17 per 100 000 at 50‐54, to 169 and 119 per 100 000 at age 80–84, for men and women respectively. No association was detected between MG and non‐haematological malignancies, neither retrospectively nor prospectively. Haematological malignancy was diagnosed in 209 (29·3%) cases before the recorded finding of MG or within the same calendar year, leaving 504 (70·7%) patients diagnosed with MGUS. Of these, 51 (10%) progressed to multiple myeloma or Waldenströms macroglobulinaemia after a mean interval of 3·8 years; mean follow‐up was 7·4 years, median 6 years. The most common immunoglobulin (Ig) class was IgG (55%), followed by IgM (32%) and IgA (13%). MGUS was a highly significant risk factor for developing haematological malignancies and the risk was significantly greater for MG of the IgA class compared with either IgG or IgM.

Epidemiology of breast cancer in families in Iceland.

The Icelandic Cancer Registry has collected 989 pedigrees of breast cancer patients since 1972. In addition to the probands, the families also include 401 other women with breast cancer, so family information exists for 1390 women with breast cancer out of a total of 2748 diagnosed with the disease from 1910 to 1988. Most of the probands have been selected with care to avoid the bias of selecting families with a known history of breast cancer. After excluding all those who did not conform to the strict selection criteria, 947 pedigrees remained for this analysis. First, second, and third degree relatives all had a significantly increased risk of breast cancer: 2.26, 1.43, and 1.49, respectively. Male relatives also had a significantly increased risk, whereas females related by marriage had not. Of the first degree relatives, sisters had the largest increase in risk. When pedigrees were classified by the age at diagnosis of breast cancer of the proband, the risk was highest in the relatives of probands who were young at diagnosis. Bilaterality of breast cancer increased the risk in relatives and the highest risk (9.04) was found in sisters of probands with bilateral disease and an age at diagnosis of first cancer of less than 45 years (95% confidence limits 4.14, 17.18). Sisters consistently have the highest risk, significantly higher than other first degree relatives. This points to an important role of shared environmental aetiological factors acting after birth and it can not yet be excluded that most of the increase in risk can be explained by this.(ABSTRACT TRUNCATED AT 250 WORDS)

Left and right sided breast cancer.

Many studies have shown that unilateral breast cancer is more frequent in the left breast than in the right. This has been investigated in the Icelandic Cancer Registry. Information on all but 18 female breast cancer cases diagnosed in the forty-year-period from 1948 to 1987, a total of 2139 cases, was used. Of these 2011 were unilateral, 1069 were in the left breast, an excess of 13%. Primary breast cancer in both breasts was diagnosed in 81 women, 35 in the left breast first, and 46 in the right breast first. The excess risk of developing cancer remains for the left breast also for women who have already lost one breast because of cancer. Information on whether their relatives had developed breast cancer existed for 1197 of these women. Patients with an affected first degree relative were of 2.54 fold risk of developing contralateral primary breast cancer, but women with no affected relative were at a reduced risk (not significant). Patients with right sided breast cancer are more likely to have a relative with breast cancer. The breast cancer status of the relatives did not influence the risk of death, so a better survival of familial cases could not be shown.