Evidence of Inbreeding Depression on Human Height

WOS:000306840400001Peer reviewe

Familial risk of prostate cancer in Iceland.

OBJECTIVE: To estimate the risk of prostate and other types of cancer among relatives of Icelandic men diagnosed with prostate cancer over a 5-year period. PATIENTS AND METHODS: The risk ratio (RR) was used to estimate the risk among relatives of 371 patients with prostate cancer, all of whom lived in Iceland and were diagnosed when alive over a 5-year interval (1983-7). Information on cancer incidence was obtained from the population-based Icelandic Cancer Registry, and information on families from a comprehensive genealogical database covering the population of Iceland. RESULTS: First-degree male relatives were at a 1.7-fold greater age-adjusted risk of prostate cancer (1832 men; 95% confidence interval, CI, 1.28-2.34). The risk was independent of proband's age at diagnosis. First-degree male relatives of patients who died from prostate cancer were at a statistically significantly greater risk of the disease (784 men; RR 2.17; 95% CI 1.34-3.53) and relatives of patients with incidental disease (T1a) were at a greater risk but not statistically significant so (261; RR 1.86; 95% CI 0.75-4.58). Female first-degree relatives were not at greater risk of breast cancer. The risk of kidney cancer was higher in first- and second-degree female relatives, with an RR (n, CI) of 2.50 (1780, 1.10-5.66) and 2.67 (5534, 1.04-6.81), respectively. The risk of kidney cancer was not statistically significantly greater in male relatives. CONCLUSION: Family history is a risk factor for prostate cancer in Icelandic men. The risk is potentially higher for relatives of patients who die from the disease. Female relatives are not at greater risk of breast cancer but they may be at greater risk of kidney cancer

Familial risk of colon and rectal cancer in Iceland: evidence for different etiologic factors?

The aim of this study was to characterize the familial risk of colon and rectal cancer using 2 population-based registries in Iceland, the Icelandic Cancer Registry and a genealogy database. The standardized incidence ratio (SIR) was used to estimate the risk among relatives of colorectal cancer index cases diagnosed in Iceland over a 46-year period (1955-2000). The 2,770 colorectal cancer patients had 23,272 first-degree relatives. Among first-degree relatives, there was an increased risk of both colon (SIR 1.47, 95% confidence interval (CI) 1.34-1.62) and rectal cancer (SIR 1.24, 95% CI 1.04-1.47). An increased risk of colon cancer was observed among siblings of colon cancer patients (SIR 2.03, 95% CI 1.76-2.33), whereas no such increase was observed for parents or offspring. Furthermore, the risk of rectal cancer was only increased among brothers (SIR 2.46 95% CI 1.46-3.89) of rectal cancer patients and not among their sisters (SIR 1.0 95% CI 0.40-2.06). The added risk of colon cancer among first-degree relatives was independent of site of colon cancer in the proband. Our results confirm that family history of colorectal cancer is a risk factor for the disease. However, family history has a different association with colon cancer than with rectal cancer, suggesting that the 2 cancer types may have different etiologic factors. Our results have implications for colon and rectal cancer screening programs

Genetic epidemiologic aspects of gastric cancer in Iceland.

BACKGROUND: Association between gastric cancer and environmental factors (diet and infections) has been established, and genetic changes are well described in adenocarcinomas of the stomach. Less is known about clinical features of hereditary gastric cancer and whether the disease is associated with family clustering. STUDY DESIGN: Family trees of patients diagnosed with gastric cancer in Iceland between 1955 and 1999 were identified in the Genealogical Database of the University of Iceland. All probands with age of onset younger than 60 years were used in the study. Families of all probands (n = 455 men and 161 women) were traced to third degree. Through linkage of the genealogic data obtained by the Icelandic Cancer Registry (between 1955 and 1999), all reported cancers were identified in those families. The expected number of cases was calculated using age-specific population rates in Iceland. RESULTS: A relative risk (RR) of 2.2 (95% confidence interval [CI] = 1.6-3.0) and 1.3 (95% CI = 1.0-1.7) for the gastric cancer risk was observed among 2,846 first- and 8,658 second-degree relatives of male probands. For female probands the corresponding relative risks were 1.6 (95% CI = 1.1-2.6, n = 7,396) and 1.4 (95% CI = 0.9-2.0, n = 2,764). The increased risk was more pronounced for relatives of men and women diagnosed with gastric cancer before the age of 50 years. A minor difference in relative risk was found between relatives of probands who were diagnosed with intestinal type or diffuse type gastric cancer. Fifty-eight families with two or more relatives with cancer were identified. In 32 families 2 relatives with gastric cancer were identified and in 26 families 3 or more relatives had gastric cancer. CONCLUSIONS: Relatives of gastric cancer patients have two- to three-fold increased risk of developing gastric cancer. The risk is elevated for both genders

A population-based study on the familial aggregation of cutaneous malignant melanoma in Iceland.

The aim of this study was to characterize the familial nature of cutaneous malignant melanoma (CMM) in Iceland. Risk ratio was used to estimate the risk among relatives of all CMM index cases diagnosed in Iceland over a 45-year period (1955-1999), using data from the National Cancer Registry and a genealogy database that covers the whole of Iceland's population. First-, second-, and third-degree relatives of CMM patients did not have an increased risk of the disease, and no added risk of other types of cancer among relatives was observed, except for thyroid cancer in first-degree male relatives. Seven individuals were diagnosed with two or more primary CMM in this period; none of these individuals had a first or second-degree relative with CMM. Altogether, 2.4% of cases were familial, as defined by commonly used criteria. In conclusion, high-penetrance susceptibility genes do not contribute much to CMM in the Icelandic population. The great majority of CMM cases in Iceland are most likely caused by the interplay between environmental causes and low-risk genes

FINE DELETION MAPPING ON THE LONG ARM OF CHROMOSOME-9 IN SPORADIC AND FAMILIAL BASAL-CELL CARCINOMAS

Basal cell carcinomas (BCCs) are the most common sporadic cancers worldwide, They are also a cardinal manifestation of a familial cancer predisposition syndrome, naevoid BCG syndrome (NBCCS), The gene responsible for NBCCS is likely to be a tumour suppressor gene and has been genetically mapped to a 2cM region between microsatellite markers, D9S196 and D9S180 at 9q22.3-q31. 101 BCCs (63 sporadic and 38 familial) were examined for loss of heterozygosity (LOH) in the candidate region of the NBCCS gene, Deletions were found in 46% and all LOH is consistent with genetic mapping of the NBCC locus, These findings strongly support the hypothesis that inactivation of the putative tumour suppressor, the NBCCS gene, is important in the formation of sporadic BCCs, One sporadic tumour indicates that the smallest region of overlap of these deletions is within the interval between D9S287 and D9S180, if this is confirmed in additional tumours, it would further narrow down the NBCCS region and exclude one candidate gene, that for the C complementation group of Fanconi anaemia, which maps proximally to D9S287, However, it would not exclude another candidate, the gene for the A complementation group of xeroderma pigmentosum (XPAC), Evidence of imprinting was also sought but preliminary data indicate that it is unlikely to occur at the NBCCS locus

BRCA2, but not BRCA1, mutations account for familial ovarian cancer in Iceland: a population-based study.

A single founder mutation in each of the BRCA genes has been identified in Iceland. The frequency of the BRCA1 G5193A and BRCA2 999del5 mutations in all ovarian cancer patients diagnosed over the period 1991-2000 was determined. Mutation status was correlated with family history, tumour morphology and age at diagnosis. Samples from 86% of cases (179 carcinomas and 74 borderline tumours) were available. In the carcinomas, BRCA1 and BRCA2 mutations were present in 1.2% and 6% of cases, respectively. No BRCA mutations were found in the borderline tumours. Odds Ratio (OR) of developing ovarian cancer was 20.65 for BRCA2 carriers. Family history of breast/ovarian cancer was present for 70% of BRCA2 carriers and approximately 14% for non-carriers with carcinoma. In conclusion, BRCA2 999del5 is present in 6% of ovarian cancer cases in Iceland and is associated with a 20-fold increase in the risk of the disease. The BRCA1 G5193A mutation is too rare to contribute significantly to ovarian cancer in Iceland

The Icelandic Cancer Project--a population-wide approach to studying cancer.

Cancer initiation and progression require a complex interaction of genetic, environmental and clinical factors. Most research, however, has been focused on only a narrow aspect of the disease process. Data generated by the Human Genome Project, as well as large-scale molecular analysis of tumours, have indicated that a more systematic approach, in which the biological information is integrated with clinical features, is warranted. There are many aspects of the Icelandic population that make it well suited for such a broad-based approach. The Icelandic Cancer Project was therefore initiated to build a population-based clinical genomics database and biobank that can be used to study cancer - from genetic predisposition to clinical outcome