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- Ericson, K, et al.
(author)
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Defective mismatch-repair in patients with multiple primary tumours including colorectal cancer
- 2003
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In: European Journal of Cancer. - 1879-0852. ; 39:2, s. 8-240
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Journal article (peer-reviewed)abstract
- Individuals with an inherited predisposition to cancer development are at an increased risk of developing multiple tumours. Hereditary non-polyposis colorectal cancer (HNPCC) is one of the most common hereditary cancer syndromes and is estimated to account for approximately 2% of colorectal cancers. However, HNPCC individuals are at an increased risk of developing other tumour types such as cancers of the endometrium, urothelium and small intestine. We have utilised a population-based regional cancer registry to identify all patients with double primary colorectal cancers and at least one additional malignancy and characterised the tumour spectrum in this patient group. We subsequently selected those 47 individuals who had developed at least four malignancies, including two colorectal cancers, for studies of the tumour characteristics associated with HNPCC. In total, these individuals developed 209 tumours, 156 of which were successfully retrieved. Microsatellite instability (MSI), a phenomenon caused by defective mismatch-repair (MMR), was identified in 63/154 (41%) evaluable tumours with a MSI-high pattern in 59 and a MSI-low pattern in four tumours. All tumours were immunohistochemically stained for the MMR proteins MLH1 and MSH2, with loss of expression in 55/63 (87%) MSI tumours and in 2/89 (2%) microsatellite stable (MSS) tumours. This loss affected MLH1 in 24 tumours and MSH2 in 33 tumours. A concordant loss of expression for the same MMR protein in several tumours from the same individual, a pattern that strongly suggests an underlying germline MMR gene mutation, was found in 17/45 (38%) patients and affected MLH1 in 8 patients and MSH2 in 9 patients. We conclude that the development of multiple primary tumours, including synchronous or metachronous colorectal cancers, is associated with an increased frequency of MSI and loss of immunohistochemical expression of MLH1 and MSH2.
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- Koul, A., et al.
(author)
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BRCA1 and BRCA2 mutations in ovarian cancer : Covariation with specific cytogenetic features
- 2000
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In: International Journal of Gynecological Cancer. - : BMJ. - 1048-891X .- 1525-1438. ; 10:4, s. 289-295
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Journal article (peer-reviewed)abstract
- We analyzed 37 primary invasive carcinomas for BRCA1 and BRCA2 mutations by screening the entire coding regions of both genes. Seven predicted truncating mutations (four in BRCA1 and three in BRCA2) and one novel BRCA1 missense variant (S1542C) were identified (8/37, 22%). Two of the BRCA1 mutations were somatic changes, whereas the remaining three BRCA1 changes and all mutations of BRCA2 were found to be of germline origin. All eight BRCA-positive tumors were serous or seropapillary carcinomas (8/27 serous tumors, 30%), and all but one were poorly differentiated. The correlation between tumor karyotype and BRCA status showed that clonal chromosomal aberrations were present in all BRCA-positive tumors (8/8) compared with 20 of 29 BRCA-negative ones. The most consistently affected region in BRCA-positive tumors was the long arm of chromosome 6; alterations within this arm with a breakpoint in band 6q21 were seen in four of five BRCA1-positive and in two of three BRCA2-positive tumors, but only in four of 20 karyotypically abnormal tumors without BRCA mutations, suggesting that the genetic pathways of tumor progression differ in the two groups. The high frequency of germline BRCA mutations detected in this pilot study (16% of 37 invasive carcinomas) points to the need for more extended analyses of population-based series of patients to determine the true contribution of these predisposing genes to the overall incidence of ovarian cancer in this population.
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- Lahmann, PH, et al.
(author)
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Birth weight is associated with postmenopausal breast cancer risk in Swedish women
- 2004
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In: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 21, s. 1666-1668
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Journal article (peer-reviewed)abstract
- There is some evidence that birth weight is associated with breast cancer. Whether this association differs between premenopausal and postmenopausal ages is still unclear. The results from this study suggest that higher birth weight is a risk factor for postmenopausal breast cancer (OR 1.06, CI 1.00-1.12, per 100 g), independent of selected early-life and adult factors.
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- Loman, N, et al.
(author)
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Family history of breast and ovarian cancers and BRCA1 and BRCA2 mutations in a population-based series of early-onset breast cancer
- 2001
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In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 93:16, s. 23-1215
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Journal article (peer-reviewed)abstract
- BACKGROUND: BRCA1 and BRCA2 are the two major susceptibility genes involved in hereditary breast cancer. This study was undertaken to provide reliable population-based estimates of genetic influence and to characterize the nature and prevalence of BRCA1 and BRCA2 germline mutations in early-onset breast cancer.METHODS: In a series comprising all women diagnosed with breast cancer under the age of 41 years in southern Sweden during 1990 through 1995 (n = 262), family history of cancer was evaluated in 95% (n = 250) of the case subjects and germline mutations in BRCA1 and BRCA2 were analyzed in 89% (n = 234). All statistical tests were two-sided.RESULTS: A total of 97 case subjects had at least one first- or second-degree relative with breast or ovarian cancer; 34 (14%; 95% confidence interval [CI] = 9.6% to 18%) cases had at least two first- or second-degree relatives, 22 (8.8%; 95%CI = 5.3% to 12%) had one first-degree relative, and 41 (16%; 95% CI = 12% to 21%) had one second-degree relative with either cancer. If two females affected with breast or ovarian cancer who were related through an unaffected male were also defined as first-degree relatives, then a higher number of case subjects, 120 (48%; 95% CI = 42% to 54%), had at least one first-degree or second-degree relative with breast or ovarian cancer. Sixteen (6.8%; 95% CI = 4.0% to 11%) BRCA1 mutation carriers and five (2.1%; 95% CI = 0.70% to 4.9%) BRCA2 mutation carriers were identified. Among case subjects with one first- or more than one first- or second-degree relative with breast or ovarian cancer, BRCA mutations were more frequent (P<.001) than among the case subjects without this degree of family history. BRCA mutations were also statistically significantly more common among women with bilateral breast cancer than among women with unilateral breast cancer (P =.002). BRCA mutations were more common among younger case subjects than among older ones (P =.0027).CONCLUSIONS: Almost half (48%) of women in southern Sweden with early-onset breast cancer have some family history of breast or ovarian cancer, and 9.0% of early-onset breast cancer cases are associated with a germline mutation in BRCA1 or BRCA2. Mutation carriers were more prevalent among young women, women with at least one first- or second-degree relative with breast or ovarian cancer, and women with bilateral breast cancer.
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- Olsson, H, et al.
(author)
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A population-based cohort study of HRT use and breast cancer in southern Sweden
- 2001
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In: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 85:5, s. 674-677
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Journal article (peer-reviewed)abstract
- 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 was a small excess of breast cancer with 434 observed and 387.69 expected (SIR = 1.12, 95% CI 1.02-1.23). Among about 3 663 ever users of HRT, there was no increase in overall tumour incidence (SIR = 0.98, 95% CI 0.86-1.12) but a significant excess of breast cancer (SIR = 1.35, 95% CI 1.09-1.64) compared with never users (SIR = 1.07, 95% CI 0.96-1.19). Breast cancer increased with increasing duration of use and for 48-120 months use the SIR was 1.92 (95% CI 1.32-2.70). There was no significant interaction with family history of breast cancer although an independent additive effect was suggested between HRT use and family history. In a Cox regression model time to breast cancer in relation to duration of HRT use was analysed adjusting for age at menarche, age at menopause, age at first full term pregnancy, parity and age at diagnosis. A significantly higher risk was seen for longer duration of HRT use compared with never users. No increased risk is seen in women beyond 5 years after stopping HRT. There was no interaction between previous use of oral contraceptives and later HRT use.
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| 7. |
- Olsson, H, et al.
(author)
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Male gynecomastia and risk for malignant tumours--a cohort study
- 2002
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In: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 2, s. 26-26
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Journal article (peer-reviewed)abstract
- BACKGROUND: Men with gynecomastia may suffer from absolute or relative estrogen excess and their risk of different malignancies may be increased. We tested whether men with gynecomastia were at greater risk of developing cancer.METHODS: A cohort was formed of all the men having a histopathological diagnosis of gynecomastia at the Department of Pathology, University of Lund, following an operation for either uni- or bilateral breast enlargement between 1970-1979. All possible causes of gynecomastia were accepted, such as endogenous or exogenous hormonal exposure as well as cases of unknown etiology. Prior to diagnosis of gynecomastia eight men had a diagnosis of prostate carcinoma, two men a diagnosis of unilateral breast cancer and one had Hodgkin's disease. These patients were included in the analyses. The final cohort of 446 men was matched to the Swedish Cancer Registry, Death Registry and General Population Registry.RESULTS: At the end of the follow up in December 1999, the cohort constituted 8375.2 person years of follow-up time. A total of 68 malignancies versus 66.07 expected were observed; SIR = 1.03 (95% CI 0.80-1.30). A significantly increased risk for testicular cancer; SIR = 5.82 (95% CI 1.20-17.00) and squamous cell carcinoma of the skin; SIR = 3.21 (95% CI 1.71-5.48) were noted. The increased risk appeared after 2 years of follow-up. A non-significantly increased risk for esophageal cancer was also seen while no new cases of male breast cancer were observed. However, in the prospective cohort, diagnostic operations for gynecomastia may substantially have reduced this riskCONCLUSIONS: There is a significant increased risk of testicular cancer and squamous cell carcinoma of the skin in men who have been operated on for gynecomastia.
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