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.     

The incidence of lymphoma in first-degree relatives of patients with Hodgkin disease and non-Hodgkin lymphoma: results and limitations of a registry-linked study

BACKGROUND: The precise incidence of familial Hodgkin disease (HD) and non-Hodgkin lymphoma (NHL) in first-degree relatives is unknown. Through record linkage using two population-based sources, the authors estimated the risk of HD and NHL in family members of lymphoma probands. METHODS: The authors identified 8,037 first-degree relatives of 2,606 lymphoma cases (28.5% HD, 71.5% NHL) treated between 1970 and 1993 in 3 hospitals in Israel via the family file of the Population Registry. The authors linked this file with the Israel Cancer Registry, then calculated the standardized incidence ratio (SIR) by dividing the observed number of cases with the expected, adjusting for age, gender, calendar year, and continent of origin. RESULTS: The family file yielded incomplete ascertainment of relatives (for 771 probands, no relatives were identified). Twenty cases of lymphoma--6 HD and 14 NHL--were identified among relatives of lymphoma patients. The SIR for HD was 1.15 (95% confidence interval [CI]: 0.42-2.51) and for NHL 1.71 (95% CI: 0.93-2.87), considering the entire population of first-degree relatives. SIRs among siblings of lymphoma probands were 3.12 (95% CI: 1.01-7.29) for HD, 2.16 (95% CI: 0.45-6.31) for NHL, and 2.68 (95% CI: 1.15-5.27) for all lymphomas. There were 4 HD/HD, 1 NHL/NHL, and 3 NHL/HD sibling pairs. For HD/HD and NHL/NHL sibling pairs, the interval between lymphoma occurrence in proband and sibling was 1-4 years, whereas for HD/NHL pairs this ranged from 16 to 21 years. CONCLUSIONS: The risk of lymphoma among siblings of lymphoma probands was over 2.5-fold that of the general population and lower among other family members. The temporal proximity of HD/HD and NHL/NHL sibling pairs argues for environmental as well as genetic etiology. This method was hampered by incomplete data.     

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.     

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.     

Risk of non-Hodgkin's lymphoma and family history of lymphatic, hematologic, and other cancers.

BACKGROUND: An elevated risk of developing non-Hodgkin's lymphoma (NHL) has been associated with a family history of NHL and several other malignancies, but the magnitude of risks and mechanisms are uncertain. METHODS: We used self-reported family history data from a recent multicenter U.S.-based case-control studies of NHL to evaluate familial aggregation of NHL with various hematolymphoproliferative and other cancers. Estimates of familial aggregation were obtained as hazard ratios (HR) that compare incidence of different cancers in first-degree relatives of NHL cases with that in the first-degree relatives of NHL controls. Limitations of the study included low participation rates (76% for cases and 52% for controls) and potential differential accuracy of recall. RESULTS: Risk of NHL was elevated in relatives of NHL cases [HR, 2.9; 95% confidence interval (95% CI), 0.95-8.53]; the aggregation seems to be stronger for siblings (HR, 7.6; 95% CI, 0.98-58.8) and for male relatives (HR, 6.2; 95% CI, 0.77-50.0). Risk of Hodgkin's lymphoma seems to be also elevated among relatives of early-onset (<50 years) NHL cases (HR, 3.2; 95% CI, 0.88-11.6). Evaluation of family history of other cancers provided modest evidence for an increased risk of melanoma of the skin (HR, 2.9; 95% CI, 1.08-7.75), pancreatic cancer (HR, 2.1; 95% CI, 0.96-4.43), stomach cancer (HR, 1.8; 95% CI, 0.91-3.63), and prostate cancer (HR, 1.3; 95% CI, 0.87-1.99). CONCLUSIONS: These results are consistent with previous findings of familial aggregation of NHL, Hodgkin's lymphoma, and a few other cancers. The pattern of male-specific and sibling-specific familial aggregation of NHL we observed, if confirmed, may shed new light on the possible mechanisms that underlie familial aggregation of the disease.     

Family history of hematopoietic and non-hematopoietic malignancies and risk of non-Hodgkin lymphoma

Background Family history of hematopoietic malignancies has been linked to the risk of non-Hodgkin lymphoma (NHL). The relationship between family history of specific hematopoietic and non-hematopoietic malignancies and the risk of NHL and by NHL subtypes are unclear. Methods We analyzed data from a population-based case–control study in Connecticut women. A total of 601 histologically confirmed NHL incident cases and 717 randomly selected controls were included in the study. Unconditional logistic regression was used to estimate the association between family cancer history and risk of NHL overall and by NHL subtypes. Results Compared to women who reported to have no family history of any malignancies in first-degree relatives, those who reported to have a family history of lymphoma (OR = 2.2, 95%CI: 1.1–4.5) or leukemia (OR = 2.5, 95%CI: 1.2–5.2) had an increased risk of NHL. The risk was higher among women who had a sibling with lymphoma or leukemia than those who had parents with lymphoma or leukemia. Several non-hematopoietic malignancies in first-degree relatives, including cancer of the lung (OR = 1.7, 95%CI: 1.1–2.6) in first-degree relatives, stomach (OR = 2.2, 95%CI: 0.8–5.9) and pancreas (OR = 2.6, 95%CI: 0.9–7.1) in parents, as well as liver (OR = 5.0, 95%CI: 1.0–24.6), breast (OR = 2.2, 95%CI: 1.3–3.9), cervix (OR = 7.5, 95%CI: 0.9–64.9), and ovary (OR = 3.5, 95%CI: 1.1–11.5) in siblings were also associated with an increased risk of NHL. Conclusions The risk associated with a family history of malignancies in first degree-relatives appears to vary by type of first-degree relatives.     

中国家族性胃癌的研究

Objective: The aim of the study was to investigate the influence of gastric cancer family history in the gastric can-cer (GC) patients. Methods: Gastric cancer family histories within second degree relatives and clinicopathological features were obtained for 497 patients. Results: Of the 497 probands, 235 probands were incorporated into familial gastdc cancer (FGC) group (there were at least two GC members in the family); 262 probands were included in the non-FGC group (relatives only affected with non-GCs). Of 614 tumors in relatives, GC was the most frequent, followed by lung cancer, esophageal can-cer, hepatocellular cancer, colorectal cancer, urogenital cancer, breast cancer, and pancreatic cancer. Most affected members aggregated within first-degree relatives. The ratio of males to females in affected first-degree relatives was usually higher in male probands. Paternal history of GC was a strong risk for GC in males, while risk of GC by maternal history of GCs was increased in females. Difference in tumor histological types between the two groups was derived from an excess of diffuse GC in non-FGC male probands. The lower site was the most frequent tumor location in all subgroups. Conclusion: Distribu-tion of associated non-GCs in a family history of GC may vary with geographic areas. GC may have different genetic and/or environmental etiology in different families, and a certain subtype may be inherited in a male-influenced fashion.     

Familial risk and clustering of nasopharyngeal carcinoma in Guangdong, China

BACKGROUND: Previous studies have suggested that genetic susceptibility may play an important role in the etiology of nasopharyngeal cancer (NPC). However, to date, few large-scale studies have been conducted on familial risk and clustering of NPC in a high-risk area of China. METHODS: In the current study, 2252 patients with NPC who were treated at the Cancer Center of Sun Yat-Sen University in Guangdong Province, China, were identified as probands. Family histories of NPC and other malignancies were observed in first-degree relatives (FDRs) and second-degree relatives, and other information was obtained through interviews. One thousand nine hundred and three Cantonese families were selected for further investigation. To assess familial aggregation, the authors used standardized incidence ratios (SIRs) to measure the risk of NPC for FDRs and compared the observed number of cases with the number predicted by population-based frequencies in the Cantonese population of Hong Kong. RESULTS: The current analysis indicated that families with > or = 3 relatives who had NPC were distributed predominantly among a high-risk subgroup of the Cantonese population in Guangdong Province and that the frequency of these families was 0.68%. An SIR of 2.09 (95% confidence interval [CI], 1.80-2.40) was observed among 13,833 FDRs in the high-risk subgroup, and a significantly elevated risk for NPC was observed in FDRs of probands with early age of onset (age < 40 years; SIR, 9.01 [95% CI, 6.10-13.30]). Furthermore, decreased risks of hepatic, lung, esophageal, gastric, and breast carcinoma, as well as malignancy of all sites, were observed among FDRs of probands with NPC when Hong Kong and Shanghai populations were used as reference groups. CONCLUSIONS: NPC tends to aggregate in Cantonese families in Guangdong Province, and the malignancies in these families appear to be site specific, with no excess of any other malignancy.     

Risk of malignancy in first-degree relatives of patients with pancreatic carcinoma

BACKGROUND: Approximately 5-10% of pancreatic carcinoma (PC) patients report a family history of the disease. In some families, mutations of tumor suppressor genes have been elucidated, but for most the causative gene remains unidentified. Counseling the families of PC patients regarding their risk of cancer remains problematic because little information is available. METHODS: The authors analyzed family history questionnaires completed by 426 unselected, sequential Mayo Clinic patients with PC. The prevalence of malignancy reported among 3355 of their first-degree relatives was compared with the Surveillance, Epidemiology, and End Results Project (SEER) 9 (2000) registry. Age-adjusted and gender-adjusted standardized incidence ratios (SIRs) were generated. RESULTS: Greater than 130,000 person-years at risk for cancer among the first-degree relatives were analyzed. The risk of PC was found to be increased among the first-degree relatives of patients with PC (SIR of 1.88; 95% confidence interval [95% CI], 1.27-2.68), as was the risk of liver carcinoma (SIR of 2.70; 95% CI, 1.51-4.46). Lymphoma (SIR of 0.28; 95% CI, 0.12-0.55), bladder carcinoma (SIR of 0.55; 95% CI, 0.31-0.89), breast carcinoma (SIR of 0.73; 95% CI, 0.57-0.92), lung carcinoma (SIR of 0.62; 95% CI, 0.47-0.80), and prostate carcinoma (SIR of 0.71; 95% CI, 0.54-0.92) were found to be underrepresented. When the proband was age < 60 years, the risk of PC to first-degree relatives was found to be increased further (SIR of 2.86; 95% CI, 1.15-5.89). In this subgroup, no other malignancies were found to be significantly increased, although the risks of melanoma (SIR of 1.73; 95% CI, 0.70-3.57), ovarian carcinoma (SIR of 2.20; 95% CI, 0.72-5.12), and colon carcinoma (SIR of 1.37; 95% CI, 0.80-2.19) were suggestive. CONCLUSIONS: There was a nearly twofold increased risk of PC in the first-degree relatives of PC probands. This risk was found to increase nearly threefold when patients were diagnosed before age 60 years. At the current time, in the absence of a pedigree suggestive of known familial cancer syndromes, the current study results do not support targeted screening for other malignancies in the first-degree relatives of patients with sporadic PC.     

Familial characteristics of autoimmune and hematologic disorders in 8,406 multiple myeloma patients: a population-based case-control study

A population-based case-control study was conducted to evaluate risk of developing multiple myeloma (MM) associated with personal history of autoimmune diseases and occurrence of autoimmune and selected hematologic disorders in first-degree relatives. Data were obtained for all (n = 8,406) MM cases diagnosed in Sweden (1958-1998), with linkable relatives, 16,543 matched controls and first-degree relatives of cases (n = 22,490) and controls (n = 44,436). Odds ratios (ORs) were calculated to quantify the risk of MM in relation to personal/family history of 32 autoimmune disorders. Familial aggregation of malignancies was evaluated in a marginal survival model using relatives as the cohort. The risk for MM was significantly elevated among subjects with a personal history of pernicious anemia (OR = 3.27; 2.22-4.83) and individuals with a family history of systemic lupus erythematosus (OR = 2.66; 1.12-6.32). Compared with controls, relative risk (RR) of MM was significantly increased (RR = 1.67; 1.02-2.73) in relatives of cases, particularly relatives of probands aged > or =65 at diagnosis (RR = 2.50; 1.19-5.27). Risks were nearly 4-fold elevated among female relatives (RR = 3.97; 1.54-10.2) and among relatives of female probands (RR = 3.74; 1.58-8.83). MM cases had more cases of monoclonal gammopathy of undetermined significance (MGUS) among their relatives than controls, but the numbers were too small to be conclusive. There was generally no increase in risk of MM in probands whose relatives had hematologic malignancies other than MM. These findings do not support a strong association between personal/familial autoimmune diseases and MM. However, MM itself shows significant familial aggregation, implicating the etiologic importance of this type of hematological neoplasm and perhaps MGUS in germ line genes.     

Influence of familial cancer history on lymphoid neoplasms risk validated in the large European case-control study epilymph

Lymphomas have a potentially important familial component; large studies using recent classification systems are lacking. Based on a multicentre case-control study in seven European countries, we recruited 2480 cases of lymphoid neoplasms (LN) and 2540 controls, matched by country, age and sex. Diagnoses were established according to the World Health Organisation (WHO) classification. We estimated odds ratios (OR) and 95% confidence intervals (CI) for cancer in first-degree relatives and for the kind of relative affected. The OR of LN for a family history of haematological cancer was 1.6 (OR=1.2-2.1). The OR was particularly high for chronic lymphocytic leukaemia (CLL) (OR=2.9 [1.9-4.5]). A familial case of lymphoma increased the risk of Hodgkin's lymphoma (HL) (OR=3.4 [1.5-7.8]). No increased risk was observed for diffuse large B-cell and follicular lymphomas. For CLL and HL, the risk was similar in parents, offspring and siblings. Our study suggests familial aggregation of CLL with a family history of haematological cancer and of HL with a family history of lymphoma. The transmission pattern suggests a dominant model of heredity.     

Familial risk of pancreatic cancer

BACKGROUND: Pancreatic cancer is the fifth leading cause of cancer-related mortality in the United STATES: Although smoking and age are known risk factors for pancreatic cancer, several case reports and case-control studies have suggested that there is also a familial risk. We evaluated whether a family history of pancreatic cancer increases the risk of pancreatic cancer in first-degree relatives and whether smoking and younger age at cancer diagnosis further increase this risk. METHODS: We conducted in-person interviews with 247 patients ("case probands") with pancreatic cancer and 420 population-based control probands to collect risk factor data and pancreatic cancer family history for 1816 first-degree relatives of the case probands and 3157 first-degree relatives of the control probands. We analyzed the data by unconditional logistic regression models, with adjustment for correlated data by use of generalized estimating equations. All statistical tests were two-sided. RESULTS: A positive family history of pancreatic cancer (i.e., being related to a case proband) or ever-smoking cigarettes approximately doubled the risk of pancreatic cancer (relative risk [RR] = 2.49; 95% confidence interval [CI] = 1.32 to 4.69; RR = 2.04; 95% CI = 1.09 to 3.83, respectively). The RR increased to 8.23 (95% CI = 2.18 to 31.07) for relatives who ever smoked and were related to a case proband who was diagnosed before age 60 years. CONCLUSION: Routine questioning of patients about a family history of pancreatic cancer, the age of onset of this cancer in their relatives, and the patient's smoking status may identify individuals at high risk of pancreatic cancer. Future research exploring the genetic and environmental interactions associated with the risk of pancreatic cancer is critically important.     

Heredity and risk of cancer of the esophagus and gastric cardia.

The importance of genetic factors in the etiology of esophageal cancer is uncertain. We addressed the question of heredity in a population-based, nationwide case-control study conducted in Sweden during 1995 through 1997. The study involved 189 patients with esophageal adenocarcinoma, 262 with cardia adenocarcinoma, 167 with esophageal squamous cell carcinoma, and, for comparison, 820 control subjects. Familial occurrence of cancer was explored at face-to-face interviews. Logistic regression, with multivariate adjustment for potential confounders, was used to calculate odds ratios (ORs), which estimated relative risk. Occurrence of esophageal cancer among first-degree relatives did not increase the risk of adenocarcinoma or squamous cell carcinoma of the esophagus. Neither were there any significant associations with familial occurrence of gastric cancer or other gastrointestinal tumors. The risk of cardia adenocarcinoma was moderately increased among persons with first-degree relatives with gastric cancer (OR, 1.6; 95% confidence interval, 1.0-2.6). Familial occurrence of any cancer was not associated with increased risks of any of the three studied tumors. In conclusion, heredity does not seem to contribute importantly to the occurrence of esophageal cancer of any histological type. A weak association between familial gastric cancer and the risk of cardia cancer may represent a genetic link.     

Explaining the familial colorectal cancer risk associated with mismatch repair (MMR)-deficient and MMR-stable tumors.

PURPOSE: There is a paucity of data quantifying the familial risk of colorectal cancer associated with mismatch repair (MMR)-deficient and MMR-stable tumors. To address this, we analyzed a population-based series of 1,042 colorectal cancer probands with verified family histories. EXPERIMENTAL DESIGN: Constitutional DNA from probands was systematically screened for MYH variants and those with cancers displaying microsatellite instability (MSI) for germ-line MMR mutations; diagnoses of familial adenomatous polyposis and juvenile polyposis were established based on clinical phenotype and mutational analysis. Familial colorectal cancer risks were enumerated from age-, sex-, and calendar-specific population incidence rates. Segregation analysis was conducted to derive a model of the residual familial aggregation of colorectal cancer. RESULTS: Germ-line predisposition to colorectal cancer was identified in 37 probands [3.4%; 95% confidence interval (95% CI), 2.4-4.6]: 29 with MLH1/MSH2 mutations, 2 with familial adenomatous polyposis, 1 with juvenile polyposis, and 5 with biallelic MYH variants. The risk of colorectal cancer in first-degree relatives of probands with MSI and MMR-stable cancers was increased 5.01-fold (95% CI, 3.73-6.59) and 1.31-fold (95% CI, 1.07-1.59), respectively. MSH2/MLH1 mutations were responsible for 50% of the overall excess familial risk and 80% of the risk associated with MSI cancers but 32% of the familial risk was unaccounted for by known loci. Genetic models based on major gene loci did not provide a better explanation of the residual familial aggregation than a simple polygenic model. CONCLUSIONS: The information from our analyses should be useful in quantifying familial risks in clinical practice and in the design of studies to identify novel disease alleles.     

Cancer risk in the relatives of patients with nasopharyngeal carcinoma—a register-based cohort study in Sweden

Background:

Little is known about cancer susceptibility among relatives of nasopharyngeal carcinoma (NPC) patients in non-endemic areas. We conducted a register-based cohort study to assess the relative risks (RRs) of cancer in families of NPC probands in Sweden.

Methods:

By linking 11 602 616 Swedish-born individuals (defined as ‘general population'') identified from national censuses to the Swedish Cancer Register and Multi-Generation Register, we identified 9157 relatives (3645 first-degree and 5512 second-degree) of 1211 NPC probands. Cancer incidence during 1961–2009 was ascertained through the Cancer Register. Relative risks of cancer in the relatives of NPC probands, compared with the rest of the general population, were calculated from Poisson regression models.

Results:

First-degree relatives had higher risks of NPC (N=2, RR=4.29, 95% confidence interval (CI)=1.07 to 17.17) and cancers of the larynx (N=5, RR=2.53, 95% CI=1.05 to 6.09), prostate (N=76, RR=1.35, 95% CI=1.07 to 1.68), and thyroid (N=10, RR=2.44, 95% CI=1.31 to 4.53) than the rest of the general population. In addition, a raised risk of cancer of the salivary glands was observed among first-degree relatives of probands with undifferentiated NPC (N=2, RR=6.64, 95% CI=1.66 to 26.57). In contrast, a decreased risk of colorectal cancer was observed in first- and second-degree relatives (N=43, RR=0.71, 95% CI=0.53 to 0.96).

Conclusion:

The increased risk of NPC and certain other cancers among first-degree relatives may be explained by shared genetic and environmental risk factors, the latter including Epstein–Barr virus infection and smoking or by increased diagnostic intensity.     

Familial occurrence of carcinoid tumors and association with other malignant neoplasms.

Carcinoid tumors are generally thought to be sporadic, except for a small proportion that occur as a part of multiple endocrine neoplasia syndromes. Data regarding the familial occurrence of carcinoid as well as its potential association with other neoplasms are limited. A chart review was conducted on patients indexed for malignant carcinoid tumor of the gastrointestinal tract seen at the Mayo Clinic between 1988 and 1996. A survey of family history of malignancies and personal history of other tumors was mailed to all eligible patients. Data for 245 patients were analyzed. Observed rates of carcinoids and other malignancies were compared with Surveillance, Epidemiology, and End Results data. Estimates of the cumulative probability for first-degree relatives developing a carcinoid tumor were calculated. Nine (3.7%) patients with carcinoid tumor had at least one first-degree relative with the same malignancy. The rate of carcinoid tumor in first-degree relatives of probands was higher (P < 0.0001) than expected based on the Surveillance, Epidemiology, and End Results population data. Cumulative probability in a first-degree relative for developing a carcinoid was calculated to be 1.5% at age 80. There was an increased risk for developing a carcinoid tumor among first-degree relatives of patients with carcinoid. Neither patients with carcinoid nor their first-degree relatives had an increased incidence of other malignancies.     

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.     

Myeloproliferative and lymphoproliferative disorders in Tasmania, 1972-80: occupational and familial aspects

All cases in a population-based series of myeloproliferative and lymphoproliferative (LP) disorders diagnosed in usual residents of Tasmania between 1972 and 1980 were asked for occupational histories and the occurrence of similar diseases in their close relatives. Occupational risks were observed for males who had farmed, mined, or worked in foundries and for women who had farmed or had been hairdressers. For individual diagnoses, the risk to farmers was seen to vary with age at diagnosis, sex, and region. With regard to familial risks, the LP and MP groups seemed to breed true, relatives being affected with a disorder from the other group not more often than would be expected by chance. The risks were of two kinds: Those to siblings and that between parent and child, particularly between mother and son. Occupational risks for the familial cases were limited to farming particularly in males diagnosed at 65 years of age or older. Females possessed elevated risks for the LP group only, and their highest relative risk was for those diagnosed before age 65. This evidence suggests that familial clustering of these disorders partly may be due to common environmental exposures in males from rural kindreds.     

Malignant tumors in first-degree relatives of cancer patients aged 0-25 years (province of Trieste,Italy)

To determine whether the occurrence of first and second primary malignancies in first-degree relatives of cancer patients aged 0-25 years (probands) differed from that in the general population, a cohort study was carried out on 860 relatives of 265 probands living in the province of Trieste, Italy. During the follow-up period (median duration = 28 years, 25th-75th percentile = 20-34), the relatives developed 103 first primary cancers vs. 88.9 expected for a standardized incidence ratio (SIR) of 1.2 (p = 0.2). Significantly elevated risks were found for melanoma in the parents of probands aged 15-25 years with melanoma (SIR = 15.0, p = 0.002), for hemolymphatic malignancies in the fathers of probands aged 0-14 years with brain tumors (SIR = 13.3, p = 0.0005) and for hemolymphatic cancers in relatives as a whole of probands aged 15-25 years with lymphomas (SIR = 4.5, p = 0.01). During the follow-up period, 7 relatives with a first primary cancer had a subsequent malignancy vs. 4.2 expected for an SIR of 1.7 (p = 0.3). Our results indicate that young cancer patients per se should not to be considered as a factor that usually increases the risk of developing malignant tumors among their first-degree relatives, except when a known cancer family syndrome or predisposition is recognized.     

Familial risk in head and neck squamous cell carcinoma diagnosed before the age of 45: a population-based study

This population-based study analyses familial risk as a factor in the development of head and neck squamous cell carcinoma before the age of 45. Two different designs were used: (1) estimation of standardised incidence ratios (SIRs) for cancer among first-degree relatives of 127 young head and neck cancer probands; and (2) estimation of odds ratios (ORs) for developing head and neck cancer associated with cancer in a first-degree relative. SIRs of cancer of the respiratory and upper digestive tract (lungs, oesophagus, and smoking-related head and neck sites [RUDT]) for first-degree relatives were 4.3 (95% confidence intervals or 95% CI of 1.6-9.5) for female patients, 1.0 (95% CI = 0.3-2.6) for male patients and 1.9 (95% CI = 0.9-3.5) for both sexes combined. ORs for head and neck cancer before the age of 45, in association with cancer of RUDT in a first-degree relative were 5.0 (95% CI = 1.4-17.3) for women, 1.1 (95% CI = 0.3-3.3) for men, and 2.0 (95% CI = 0.9-4.4) for both sexes combined. Hence, when analysing both sexes combined, our familial risk estimates for head and neck cancer showed non-significant increases. An explanation for the unexpected sex asymmetry in familial risk could be an interaction between inherent cancer susceptibility and a female biological characteristic. Alternatively, it could be artefacts caused by differences in familial smoking habits.