Familial aggregation of astrocytoma in northern Sweden: an epidemiological cohort study

This population-based cohort study investigated the occurrence of familial astrocytoma among first-degree relatives of patients with astrocytoma diagnosed between 1985 and 1993 in the northern region of Sweden. The 432 cases received a questionnaire. They were asked to provide names and cancer diagnoses of first-degree relatives. Of the 297 answering, a cohort was constructed of their 1,890 first-degree relatives (FDR). A significantly increased risk [standardized incidence ratio, SIR = 2.12, 95% confidence interval (CI) = 1.18-3.49] was shown for developing primary brain tumors (PBT). In 4.7% (14/297) of the families, a PBT was found. Interestingly, the increased risk was for astrocytoma only (SIR = 3.12, 95% CI 1.42-5.92), and not for other PBT (SIR 0.90, 95% CI 0.18-2.64). When the cohort was divided according to the median age of proband, most of the increased risk was restricted to the younger cohort (SIR = 4.71, 95% CI 1.52-10.99). Surprisingly, a significantly decreased risk for breast cancer and colon cancer was shown. The finding that the increased risk is restricted to astrocytoma only is a novel one. This study implies that familial aggregation of astrocytoma exists; the familial clustering occurs in a small fraction of astrocytoma, and might be explained by inherited factors.     

Cancer risk in families with hereditary prostate carcinoma

BACKGROUND: Little is known regarding the clinical features of hereditary prostate carcinoma (HPC) and whether other malignancies are associated with this disease. The aim of this study was to investigate whether tumors other than prostate carcinoma aggregate in families with HPC or whether this disease can be considered site specific. METHODS: From 62 Swedish families with HPC, a cohort was constructed of 1364 first-degree relatives of the men with prostate carcinoma in these families. Through linkage to the Swedish Cancer Register, all reported cancer between 1958 and 1996 was identified. The expected number of cases was calculated by using the population rates in Sweden. RESULTS: A standardized incidence ratio (SIR) of 1. 16 (95% confidence interval [95% CI], 0.97-1.38) for the overall cancer risk was observed among the 1364 first-degree relatives. However, significant increased risks were noticed for gastric carcinoma (SIR, 2.78; 95% CI, 1.59-4.52), for breast carcinoma in women (SIR, 1.58; 95% CI, 1.01-2.35), and for kidney carcinoma (SIR, 2.51; 95% CI, 1.15-4.77).The excess risk for breast carcinoma was even more pronounced among women before the age of 65 years in families with earlier onset prostate carcinoma (SIR, 3.64; 95% CI, 1. 66-6.91). Seven families with at least two or more relatives with breast, gastric, or kidney carcinoma were identified, and, in one family, four relatives with early onset gastric carcinoma were observed. CONCLUSIONS: In most of the families with HPC, the disease appears to be "site specific," with no excess of other malignancies. However, in a subset of families, a significant aggregation of prostate carcinoma together with breast carcinoma and/or gastric carcinoma was observed that may have been caused by a common germline mutation in a cancer susceptibility gene.     

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.     

Increased risk of cancer among siblings of long-term childhood cancer survivors: a report from the childhood cancer survivor study.

We determined risk of cancer among first-degree relatives of 5-year survivors of childhood leukemia, lymphoma, central nervous system tumors, sarcomas, Wilms' tumor, and neuroblastoma. Subjects were 13,703 participants in the Childhood Cancer Survivor Study. Family history was collected on 56,759 first-degree relatives using a self-reported questionnaire. Incidence was compared with age- and sex-specific rates using the U.S. Surveillance, Epidemiology and End Results program. Siblings of the survivors had an increased risk of cancer [standardized incidence ratio (SIR), 1.5; 95% confidence interval (95% CI), 1.35-1.7]. Risk was elevated for siblings of probands of leukemia (SIR, 1.3; 95% CI, 1.0-1.6), Hodgkin's disease (SIR, 1.5; 95% CI, 1.2-1.9), non-Hodgkin's lymphoma (SIR, 1.8; 95% CI, 1.3-2.5), Wilms' tumor (SIR, 1.9; 95% CI, 1.2-3.2), soft tissue sarcoma (SIR, 1.5; 95% CI, 1.0-2.2), and bone tumors (SIR, 1.6; 95% CI, 1.2-2.2). Cancer risk was elevated in siblings (SIR, 2.4; 95% CI, 1.5-3.7) and offspring (SIR, 15.0; 95% CI, 5.3-42.9) of probands with second malignant neoplasms (SMN) compared with relatives of probands without SMNs. Siblings of probands with leukemia, Hodgkin's disease, neuroblastoma, and Wilms' tumor had elevated risks for the same malignancies. Parents had no increased risk (fathers' SIR, 0.7; 95% CI, 0.7-0.8; mothers' SIR, 0.9; 95% CI, 0.9-1.0). Seventy percent of siblings' cancers developed in adulthood. These findings suggest that familial cancer syndromes may be revealed as this cohort and family members age and with accrual of more offspring and subjects with SMNs.     

Increased risk of incident pancreatic cancer among first-degree relatives of patients with familial pancreatic cancer.

It has been estimated that familial aggregation and genetic susceptibility play a role in as many as 10% of patients with pancreatic cancer (PC). The quantified prospective risk of PC among first-degree relatives of PC patients has not been investigated. Families enrolled in the National Familial Pancreas Tumor Registry (NFPTR) prior to September 1, 1998 were followed to estimate the risk and incidence of PC among first-degree relatives of patients with PC. Analyses were performed separately on kindreds with at least two first-degree relatives with PC (familial pancreatic carcinoma (PC); n = 150) at the time the kindred was enrolled in the NFPTR and on kindreds without a pair of affected first-degree relatives (sporadic PC; n = 191). A subanalysis was performed on familial PC kindreds containing three or more affected members at the time of enrollment in the NFPTR (n = 52). Risk was estimated by comparing observed new cases of PC during the observation period with expected numbers based on the United States population-based Surveillance, Epidemiology and End Results program data. Incidence was estimated using person-years risk analyses. During the observational period, six incident PCs developed in the first-degree relatives: two in the sporadic PC kindreds, and four in the familial PC kindreds. The PC risk in the sporadic PC kindreds was not significantly greater than expected [observed/expected = 6.5 (95% CI = 0.78-23.3)] with an incidence rate of 24.5/10(5)/ year. There was a significantly increased 18-fold risk (95% CI = 4.74-44.5) of PC among first-degree relatives in familial PC kindreds, with an incidence of 76.0/10(5)/year. In the subset of familial PC kindreds with three or more affected family members at the time of enrollment, there was a 57-fold (95% CI = 12.4-175) increased risk of PC and an incidence of 301.4/10(5)/year compared with the Surveillance, Epidemiology and End Result age-adjusted incidence of PC in the U.S. (8.8/10(5)/year). When stratified by age, the risk was largely confined to relatives over the age of 60. This study is the first analysis of incident PC occurring in familial PC kindreds. The risk and incidence of PC is exceptionally high among at-risk first-degree relatives in familial PC kindreds in which at least three first-degree relatives have already been diagnosed with PC. Familial PC kindreds are a reasonable high-risk group for PC screening and chemoprevention research.     

Familial aggregation of early-onset cancers in early-onset breast cancer families

The risk of early-onset (EO) breast cancer is known to be increased in relatives of EO breast cancer patients, but less is known about the familial risk of other EO cancers. We assessed familial risks of EO cancers (aged ≤40 years) other than breast cancer in 54 753 relatives of 5562 women with EO breast cancer (probands) by using a population-based cohort from Finland. Standardized incidence ratios (SIRs) and 95% confidence intervals (CI) were estimated by using gender-, age- and period-specific cancer incidences of the general population as reference. The risk of any cancer excluding breast cancer in first-degree relatives was comparable to population cancer risk (SIR 0.99, 95% CI: 0.84-1.16). Siblings' children of women with EO breast cancer were at an elevated risk of EO testicular and ovarian cancer (SIR = 1.74, 95% CI: 1.07-2.69 and 2.69, 95% CI: 1.08-5.53, respectively). The risk of EO pancreatic cancer was elevated in siblings of the probands (7.61, 95% CI: 1.57-22.23) and an increased risk of any other cancer than breast cancer was observed in children of the probands (1.27, 95% CI: 1.03-1.55). In conclusion, relatives of women with EO breast cancer are at higher familial risk of certain discordant EO cancers, with the risk extending beyond first-degree relatives.     

Familial occurrence of nonmedullary thyroid cancer: a population-based study of 5673 first-degree relatives of thyroid cancer patients from Norway.

The purpose of this study was to estimate the occurrence of familial nonmedullary thyroid cancer (FNMTC) in a large population-based study. Of the 5274 cases of thyroid cancer on record in the Norwegian Cancer Registry between 1960 and 1995, a total of 1025 patients could be identified with verified thyroid cancer, a unique personal identification number, and a link to at least one parent. For patients with nonmedullary carcinoma, 5457 first-degree relatives in 970 families were found, compared with 216 first-degree relatives in 37 families for the medullary cancers. A standardized incidence ratio (SIR) was calculated among the relatives based on rates from the Cancer Registry of Norway. A significantly increased risk of thyroid cancer was found among the 5457 relatives of nonmedullary index cases, both for males [SIR, 5.2; confidence interval (CI), 2.1-10.7; 7 cases] and females (SIR, 4.9; CI, 3.0-7.7; 19 cases). All of these 26 thyroid cancer cases were of the nonmedullary type. Furthermore, an increased risk was found among 4282 relatives of papillary index cases, for both males (SIR, 5.8; CI, 2.1-12.6; 6 cases) and females (SIR, 4.0; CI, 2.1-7.1; 12 cases). The 36 familial papillary thyroid cancer patients had an average age at diagnosis of 43 years. Genetic influence is probably only modest for the familial nonmedullary cases and clearly weaker than for the classic familial type of medullary thyroid cancer.     

Risk of a new primary cancer among patients with lung cancer of different histological types

The risk of a new primary cancer (NPC) among 77548 Finnish lung cancer patients from 1953 to 1995 was analysed by the histological type of the lung cancer. The relative risks were expressed as standardised incidence ratios (SIR, ratio of the observed and expected numbers of cases). During the follow-up, 1148 NPCs were observed among men and 152 among women. After exclusion of lung cancers, the risk of NPC was elevated in both males (SIR 1.07; 95% confidence interval (CI) 1.00-1.14) and females (SIR 1.21; 95% CI 1.02-1.42). The excess was larger among lung cancer patients with small-cell carcinoma and adenocarcinoma than those with squamous-cell carcinoma. In all major histological groups of lung cancer, significant excess risks were found for cancers of the larynx (SIRs 2.94-4.25), and bladder (SIRs 2.16-2.86). Significantly elevated SIRs were also found for cancers of the stomach (SIR 1.42; 95% CI 1.12-1.76) and kidney (SIR 2.18; 95% CI 1.56-2.97) in squamous-cell carcinoma; for brain tumours (SIR 3.26; 95% CI 1.20-7.09) in small-cell carcinoma; and for cancers of the prostate (SIR 1.68; 95% CI 1.21-2.27) and thyroid (SIR 3.79; 95% CI 1.23-8.85), and brain tumours (SIR 2.34; 95% CI 1.07-4.43) in adenocarcinoma. The risk of contracting NPC at sites where the majority of tumours are adenocarcinomas was elevated among patients with adenocarcinoma of the lung, but not among squamous-cell or small-cell carcinoma patients. In adenocarcinoma, the excess risks of several smoking-related cancers tended to be somewhat lower than those in the other two histological categories. The relative risk of a NPC among patients diagnosed with lung cancer in 1985-1995 was higher than that of patients from earlier periods in all comparable follow-up categories (up to 10 years), possibly suggesting that the increased use of cytostatic drugs had increased the risk of NPC.     

Site-specific familial aggregation of prostate cancer

Over the last decade, epidemiologic evidence has accumulated in favor of a significant but heterogeneous hereditary component in prostate cancer (PC) susceptibility. In order to map and clone PC susceptibility genes, stratification of PC families into genetically homogeneous groups appears to be a key issue. Subset definition based on age at diagnosis, presumed mode of inheritance, number of affecteds per family and coaggregation of PC with other cancers has already proven successful in some studies. Previously, the finding of the coaggregation of malignancies of the central nervous system within PC families helped to link a prostate-brain cancer susceptibility gene (CAPB) to chromosome 1p36. In this study, we evaluate the risk of PC and malignancies at other sites among first-degree relatives of a large population-based group of Dutch PC patients. A population-based family case-control study was initiated that included Caucasian PC patients newly diagnosed between July 1996 and December 1999. Information on 12,575 first-degree relatives of 704 PC patients and 1,371 controls was collected through postal questionnaires and telephone interviews. All reported PC in first-degree relatives was verified through medical records. In our population, PC has a strong familial component that is reflected by a 2.9-fold increased risk (95% CI = 2.2-3.9) of PC for first-degree relatives of PC patients. This familial risk was somewhat higher among brothers (hazard ratio = 3.9; 95% CI = 2.4-6.4) compared to fathers (hazard ratio = 2.5; 95% CI = 1.7-3.6). Cancers at other sites did not coaggregate with PC. Our data suggest that familial PC, at least in this Western European population, is site-specific, not part of an inherited cancer syndrome.     

Sex- and kindred-specific familial risk of non-Hodgkin's lymphoma.

A family history of non-Hodgkin's lymphoma (NHL) confers increased risk of NHL, but it is unknown whether the excess risk in males and females varies by the sex or kinship of the affected relative. We linked nationwide Swedish registries to identify parents and siblings of NHL patients who developed NHL between January 1, 1961 and December 31, 2002. In males, parental risks were approximately the same from fathers and mothers, whereas sibling risks were higher from brothers [standardized incidence ratio (SIR), 1.8; 95% confidence interval (95% CI), 1.0-2.9] than sisters (SIR, 0.9; 95% CI, 0.2-1.9). In females, parental and sibling risks were higher from same-sex relatives (SIR from mothers, 1.9; 95% CI, 1.2-2.7; SIR from sisters, 6.3; 95% CI, 4.0-9.3) than from opposite-sex relatives (SIR from fathers, 1.2; 95% CI, 0.7-1.9; SIR from brothers, 0.7; 95% CI, 0.2-1.6). These findings did not vary substantially by the age of diagnosis of the offspring. Risk of NHL in offspring was also increased among those with a parent diagnosed with multiple myeloma or leukemia. The relative risk of NHL among those with a parent diagnosed with any hematopoietic cancer was 1.5 (95% CI, 1.4-1.7) and that for having a sibling with any hematopoietic cancer was also 1.5 (95% CI, 1.2-1.9). Our results suggest that part of the familial risk of NHL may be attributable to shared environmental exposures, particularly between same-sex siblings.     

Hematopoietic and lymphatic cancers in relatives of patients with infectious mononucleosis

BACKGROUND: Young adults with a history of Epstein-Barr virus (EBV)-related infectious mononucleosis have an increased risk for Hodgkin's lymphoma. EBV is detected in Hodgkin's lymphoma Reed-Sternberg cells from some patients, but in young adult patients, it is detected at a relatively low frequency in these cells. Hodgkin's lymphoma and infectious mononucleosis are both associated with high social class, and unknown confounding factors that are also associated with socioeconomic status might explain or contribute to the apparent association between these diseases. To indirectly assess the importance of socioeconomic status on the association between these diseases, we determined the risk for hematopoietic and lymphatic cancers in first-degree relatives of patients with confirmed EBV-related infectious mononucleosis. METHODS: We identified parents, siblings, and offspring of 17,045 persons with serologically confirmed EBV-related infectious mononucleosis. Subjects in these cohorts were linked with the population-based Danish Cancer Register to identify those developing hematopoietic/lymphatic cancers after the index patient was diagnosed with infectious mononucleosis. The relative risk for cancer in the infectious mononucleosis family members was expressed as standardized incidence ratios (SIRs; i.e., the ratio between the number of cancers observed and the number of cancers expected, obtained from age-specific, sex-specific, and period-specific incidence rates). RESULTS: We identified 8052 parents, 5264 siblings, and 28,605 offspring of patients with EBV-related infectious mononucleosis who were followed for a total of 892,213 person-years at risk. The risk for Hodgkin's lymphoma was unaltered in the combined group of first-degree relatives of these patients (SIR = 0.99; 95% confidence interval [95% CI] = 0.62 to 1.59; number of cases [n] = 17), in the group of parents (SIR = 0.83; 95% CI = 0.31 to 2.22; n = 4), in the group of siblings (SIR = 0.96; 95% CI = 0.31 to 2.97; n = 3), and in the group of offspring (SIR = 1.08; 95% CI = 0.58 to 2.02; n = 10). CONCLUSION: The unremarkable risk for Hodgkin's lymphoma in family members of patients with EBV-related infectious mononucleosis indicates that socioeconomic confounding is an unlikely explanation for the association between EBV-related infectious mononucleosis and Hodgkin's lymphoma.     

Breast and ovarian cancer in relatives of cancer patients, with and without BRCA mutations.

BACKGROUND: First-degree relatives of patients with breast or ovarian cancer have increased risks for these cancers. Little is known about how their risks vary with the patient's cancer site, carrier status for predisposing genetic mutations, or age at cancer diagnosis. METHODS: We evaluated breast and ovarian cancer incidence in 2,935 female first-degree relatives of non-Hispanic White female patients with incident invasive cancers of the breast (n = 669) or ovary (n = 339) who were recruited from a population-based cancer registry in northern California. Breast cancer patients were tested for BRCA1 and BRCA2 mutations. Ovarian cancer patients were tested for BRCA1 mutations. We estimated standardized incidence ratios (SIR) and 95% confidence intervals (95% CI) for breast and ovarian cancer among the relatives according to the patient's mutation status, cancer site, and age at cancer diagnosis. RESULTS: In families of patients who were negative or untested for BRCA1 or BRCA2 mutations, risks were elevated only for the patient's cancer site. The breast cancer SIR was 1.5 (95% CI, 1.2-1.8) for relatives of breast cancer patients, compared with 1.1 (95% CI, 0.8-1.6) for relatives of ovarian cancer patients (P = 0.12 for difference by patient's cancer site). The ovarian cancer SIR was 0.9 (95% CI, 0.5-1.4) for relatives of breast cancer patients, compared with 1.9 (95% CI, 1.0-4.0) for relatives of ovarian cancer patients (P = 0.04 for difference by site). In families of BRCA1-positive patients, relatives' risks also correlated with the patient's cancer site. The breast cancer SIR was 10.6 (95% CI, 5.2-21.6) for relatives of breast cancer patients, compared with 3.3 (95% CI, 1.4-7.3) for relatives of ovarian cancer patients (two-sided P = 0.02 for difference by site). The ovarian cancer SIR was 7.9 (95% CI, 1.2-53.0) for relatives of breast cancer patients, compared with 11.3 (3.6-35.9) for relatives of ovarian cancer patients (two-sided P = 0.37 for difference by site). Relatives' risks were independent of patients' ages at diagnosis, with one exception: In families ascertained through a breast cancer patient without BRCA mutations, breast cancer risks were higher if the patient had been diagnosed before age 40 years. CONCLUSION: In families of patients with and without BRCA1 mutations, breast and ovarian cancer risks correlate with the patient's cancer site. Moreover, in families of breast cancer patients without BRCA mutations, breast cancer risk depends on the patient's age at diagnosis. These patterns support the presence of genes that modify risk specific to cancer site, in both carriers and noncarriers of BRCA1 and BRCA2 mutations.     

Familial aggregation and heterogeneity of non-Hodgkin lymphoma in population-based samples.

The importance of genetic factors in the etiology of non-Hodgkin lymphoma (NHL) is suggested by case-control and cohort studies. Most previous studies have been too small to estimate accurately risks of specific categories of lymphoproliferative malignancies in relatives of NHL cases or to quantify the contribution of NHL case characteristics to familial risk. We have overcome sample size limitations and potential recall bias by using large databases from Sweden and Denmark. Diagnoses of lymphoproliferative malignancies were compared in 70,006 first-degree relatives of 26,089 NHL cases (including 7,432 with subtype information) versus 161,352 first-degree relatives of 58,960 matched controls. Relatives of NHL cases were at significantly increased risk for NHL [relative risk (RR), 1.73; 95% confidence interval (95% CI), 1.39-2.15], Hodgkin lymphoma (RR, 1.41; 95% CI, 1.0-1.97), and nonsignificantly for chronic lymphocytic leukemia (CLL; RR, 1.31; 95% CI, 0.93-1.85). No increased risk was found for multiple myeloma among case relatives. Findings with respect to siblings compared with parents and offspring or with respect to age at diagnosis of proband were inconsistent. In both populations, relatives of cases with an aggressive NHL subtype were at substantially increased risk of NHL (combined RR, 3.56; 95% CI, 1.80-7.02). We conclude that NHL has an important familial component, which is shared with Hodgkin lymphoma and CLL. We estimate that the absolute lifetime risk for a first-degree relative of an NHL case to develop NHL is 3.6% (compared with a population risk of 2.1%) and higher if the index case had an aggressive subtype of NHL.     

Relatives of Prostate Cancer Patients have an Increased Risk of Prostate and Stomach Cancers: A Population-Based, Cancer Registry study in Finland

Objective: Five to ten percent of prostate cancers may be caused by inherited genetic defects. In order to explore the nature of inherited cancer risks in the genetically homogeneous Finnish population, we investigated the incidence of prostate cancer and other cancers in first-degree relatives of prostate cancer patients by linking the population-based parish records on relatives with the Finnish Cancer Registry (FCR) data. Methods: The study population was composed of first-degree relatives of two groups of prostate cancer patients diagnosed in Finland during 1988–1993: (1) all early-onset (60years) patients (n=557) from the entire country, (2) a sample (n=989) of prostate cancer patients diagnosed at an age of >60years. A total of 11,427 first-degree relatives were identified through parish records, and their cancer incidence was determined based on a total of 299,970 person-years. Standardized incidence ratios (SIR) were calculated based on expected cancer rates in the general population. Results: The SIR of prostate cancer was increased in both Cohort 1 (2.5, 95% CI 1.9–3.2) and Cohort 2 (1.7, 95% CI 1.4–2.1). The risk of prostate cancer was high for relatives of patients diagnosed at an early age, and then leveled off for patients in the median age of prostate cancer diagnosis (70–79 years). However, the prostate cancer risk for relatives of patients diagnosed 80years was again statistically significantly elevated (SIR 1.8, 95% CI 1.3–2.6), suggesting a contribution of genetic factors to prostate cancer also at a late age of onset. Gastric cancer was the only other cancer type with a significantly elevated risk among the relatives. Increased risk of gastric cancer was seen only in male relatives of prostate cancer patients diagnosed at an early age, with the highest risk detected for the male relatives of prostate cancer patients diagnosed at an age of 55 years or less (SIR 5.0, 95% CI 2.8–8.2). Conclusions: Our population-based study indicates that hereditary factors may play an important role in the development of prostate cancer among the relatives of men diagnosed both at younger and older ages. This finding is relevant in the context of our observations that HPCX (hereditary prostate cancer susceptibility locus on Xq27-28) linkage in Finland is found exclusively among families with late age of onset. The association of gastric cancer with prostate cancer has not been reported previously, and may reflect the effects of a novel predisposition locus, which increases the risk to both of these common tumor types.     

Family history of cancer and the risk of prostate cancer and benign prostatic hyperplasia

We analysed the relation between family history of cancer in first-degree relatives and risk of prostate cancer (PC) and benign prostatic hyperplasia (BPH) using data from a multicentric case-control study conducted in Italy from 1991 to 2002 on 1,294 cases of incident, histologically confirmed PC, 1,369 cases of BPH and 1,451 men admitted to the same network of hospitals for acute, nonneoplastic conditions. Unconditional logistic regression was used to estimate odds ratios (OR) of PC and BPH, adjusted for age and other confounders. Men with a family history of PC had an OR of PC of 4.0 (95% confidence interval [CI] 2.5-6.5), and the risk was higher when the proband was younger, when 2 or more relatives were affected or when the affected relative was a brother. The risk of PC was also increased in men with a family history of cancer of the ovary (OR = 6.2, 95% CI 1.2-32), bladder (OR = 3.5, 95% CI 1.6-7.4) and kidney (OR = 3.1, 95% CI 1.1-8.5). An involvement of breast/ovarian cancer predisposition genes in a small proportion of PCs was suggested by the cluster of these cancers in female relatives of a few PC cases. The risk of BPH was increased in men with a family history of bladder cancer (OR = 2.2, 95% CI 1.0-5.0) but not PC (OR = 1.2, 95% CI 0.7-2.2). Our study adds further information on the association of family history of cancer and risk of PC and is, to our knowledge, the first comprehensive epidemiologic information on family history of cancer and risk of BPH.     

Cancer incidence in the US radiologic technologists health study, 1983-1998

BACKGROUND: Workers exposed to low doses of radiation can provide information regarding cancer risks that are of public concern. However, characterizing risk at low doses requires large populations and ideally should include a large proportion of women, both of which rarely are available. METHODS: Among 90305 radiologic technologists in the U.S. (77% women) who were followed during 1983-1998, data concerning incident cancer occurrence was obtained from mailed questionnaires and from death records. Standardized incidence ratios (SIRs) were computed using age-specific, gender-specific, race-specific, and calendar year-specific cancer rates from the Surveillance, Epidemiology, and End Results Program. RESULTS: The SIR for all cancers in both genders combined was 1.04 (95% confidence interval [95% CI], 1.00-1.07; n = 3292 technologists). Female technologists had an elevated risk for all solid tumors combined (SIR = 1.06; 95% CI, 1.02-1.10; n = 2168 women) and for breast cancers (SIR = 1.16; 95% CI, 1.09-1.23; n = 970 women), melanoma (SIR = 1.66; 95% CI, 1.43-1.89; n = 181 women), and thyroid cancers (SIR = 1.54; 95% CI, 1.24-1.83; n = 107 women). Male technologists experienced a decreased risk for solid tumors (SIR = 0.92; 95% CI, 0.85-0.98; n = 755 men); however, melanoma (SIR = 1.39; 95% CI, 1.00-1.79; n = 56 men) and thyroid cancers (SIR = 2.23; 95% CI, 1.29-3.59; n = 17 men) were increased. Among both genders, the risks were decreased for buccal cavity/pharyngeal cancers (SIR = 0.73; 95% CI, 0.55-0.90; n = 54 technologists), rectal cancers (SIR = 0.62; 95% CI 0.48-0.76; n = 53 technologists), and lung cancers (SIR = 0.77, 95% CI, 0.70-0.85; n = 307 technologists). CONCLUSIONS: The elevated risk for breast cancer may have been related to occupational radiation exposure. The observed excesses of melanoma and thyroid cancers may reflect, at least in part, earlier detection among medical workers with easy access to health care.     

Family history of hemolymphopoietic and other cancers and risk of non-Hodgkin's lymphoma.

We investigated the risk of lymphomas, hemolymphopoietic (HLP) cancers (including lymphomas), and non-HLP cancers in first-degree relatives of non-Hodgkin's lymphoma (NHL) cases in an Italian case-control study on 225 patients (median age, 59 years) with a new diagnosis of NHL and 504 hospital controls (median age, 63 years), admitted for a wide spectrum of acute, nonneoplastic, nonimmune conditions. We estimated odds ratios (OR) adjusted for sex, age, family size, and other potential confounders. We also built the cohort of all first-degree relatives and computed age and sex adjusted hazard ratios (HR) using proportional hazard models. A history of lymphoma in first-degree relatives was reported by 5 NHL cases and 3 controls [OR, 3.2; 95% confidence interval (95% CI), 0.7-14.4] whereas 14 cases and 11 controls reported a family history of HLP cancers (OR, 3.0; 95% CI, 1.2-7.0). The HR of relatives of NHL cases, compared with relatives of controls, was 4.5 (95% CI, 1.1-18.8) for lymphomas, 3.5 (95% CI, 1.5-7.4) for HLP cancers, 1.6 (95% CI, 1.3-2.0) for all cancers, and 1.0 (95% CI, 0.9-1.1) for all causes of deaths. The HRs were higher for relatives of NHL cases diagnosed before the age of 50 years: 7.1 for HLP cancers, 2.0 for all cancers, and 1.6 for all deaths. A family history of cancer of the liver (OR, 2.1; 95% CI, 1.0-4.2), breast (OR, 2.0; 95% CI, 1.0-3.6), and kidney (OR, 4.6; 95% CI, 1.0-20.9) increased NHL risk. The OR was also elevated for all cancer sites (OR, 1.7 95% CI, 1.2-2.4) and the risk increased with the number of affected relatives also when HLP cancers were excluded.     

Familial risk of hepatocellular carcinoma among chronic hepatitis B carriers and their relatives

BACKGROUND: Familial predisposition as a risk factor for hepatocellular carcinoma (HCC) in hepatitis B virus (HBV) carriers has not been thoroughly explored. METHODS: The HCC risk associated with having parents and/or siblings with HCC was evaluated by use of a cohort study of 4808 male HBV carriers. A case-control family study was also conducted on data from first-degree relatives of 553 HBV carriers who had newly diagnosed HCC (case subjects) and 4684 HBV carriers without HCC (control subjects). RESULTS: In the cohort study, HBV carriers with a family history of HCC had a multivariate-adjusted rate ratio for HCC of 2.41 (95% confidence interval [CI] = 1.47-3.95) compared with HBV carriers without a family history of HCC. For carriers with two or more affected relatives, the ratio increased to 5.55 (95% CI = 2.02-15.26). Cumulative HCC risk by age 70 years was 235.6 per 1000 (95% CI = 95. 3-375.9 per 1000) for HBV carriers with family history compared with 88.9 per 1000 (95% CI = 67.9-109.9 per 1000) for those without. In the case-control family study, first-degree relatives of case subjects were more likely to have HCC (age-sex-adjusted odds ratio [OR] = 2.57; 95% CI = 2.03-3.25) than first-degree relatives of control subjects. The excess risk of HCC among relatives was particularly evident in siblings (sisters-age-adjusted OR = 4.55 [95% CI = 2.22-9.31]; brothers-age-adjusted OR = 3.73 [95% CI = 2. 64-5.27]), but it was also observed in parents. The cumulative risk of HCC to age 80 years was 83.0 per 1000 among relatives of case subjects and 42.0 per 1000 among relatives of control subjects. Among relatives of case subjects, the cumulative risk of HCC was greater if the case subjects were diagnosed before age 50 years (two-sided P =.047). Liver cirrhosis was 2.29 (95% CI = 1.68-3.11) times more frequent in relatives of case subjects than in relatives of control subjects. CONCLUSIONS: First-degree relatives of patients with HBV-related HCC appear to be at increased risk of HCC and should be considered in the formulation of HCC-screening programs.     

Cancer risks for the relatives of colorectal cancer cases with a methylated MLH1 promoter region: data from the Colorectal Cancer Family Registry

Methylation of the MLH1 gene promoter region is an underlying cause of colorectal cancer (CRC) with high microsatellite instability (MSI-H) diagnosed in persons without a germ line mutation in a mismatch repair (MMR) gene (non-Lynch Syndrome CRC). It is unclear whether relatives of CRC cases with MLH1 methylation have an increased risk of colorectal or other cancers. In this retrospective cohort study, we assessed risk of CRC and other cancers for the first- and second-degree relatives of CRC cases with a methylated MLH1 gene, by comparing observed numbers of cases with those expected on the basis of age-, sex-, and country-specific cancer incidences (standardized incidence ratios). The cohort consisted of 3,128 first- and second-degree relatives of the 233 MLH1-methylated CRC cases with no MMR or MUTYH gene mutations. The standardized incidence ratio (SIR) for CRC was 1.60 [95% confidence interval (CI), 1.22-2.16] for first-degree relatives and 1.08 (0.74-1.60) for second-degree relatives. The SIR for gastric cancer was 2.58 (1.52-4.71) for first-degree relatives and 4.52 (2.23-10.61) for second-degree relatives and, for ovarian cancer, it was 2.16 (1.29-3.86) for first-degree relatives. The risk of liver cancer was also increased significantly in first-degree relatives but the estimate was on the basis of only two cases. These data imply that relatives of CRC cases with MLH1 methylation may be at increased risk of CRC and stomach cancer and possibly ovarian and liver cancer, suggesting that there may be a heritable factor for CRC and other cancers associated with MLH1 methylation in non-Lynch syndrome CRCs.     

Family history of cancer and risk of lung cancer among nonsmoking Chinese women.

The relationship between family cancer history in first-degree relatives and risk of lung cancer was evaluated among a population-based cohort of 71,392 female nonsmokers in Shanghai, China. A total of 179 newly diagnosed lung cancer patients were identified during 441,410 person-years of follow-up. Lung cancer risk was not elevated among those with a family history of lung cancer. However, risk of lung cancer was increased among subjects who had two or more first-degree relatives with any type of cancers {rate ratio [RR], 1.95 [95% confidence intervals (95% CI), 1.08-3.54] for two relatives with any cancers and RR, 3.17 [95% CI, 1.00-10.03] for three or more relatives with any cancer}. Having a family history of colorectal cancer (RR, 2.38; 95% CI, 1.21-4.70) and having siblings with stomach cancer (RR, 2.16; 95% CI, 1.01-4.65) and pancreatic cancer (RR, 4.19; 95% CI, 1.04-16.95) were also found to be associated with lung cancer risk. This cohort study indicated a moderate association of lung cancer risk with a family cancer history in general, but not with a family history of lung cancer specifically. The associations were stronger when a sibling, rather than a parent, was affected. The apparent link between lung cancer risk and a family history of colorectal, stomach, and pancreas cancers may be worth further investigation.