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.     

Familial aggregation of Hodgkin lymphoma and related tumors

BACKGROUND: The importance of genetic factors in the etiology of Hodgkin lymphoma (HL) has been suggested by family and population studies. However, the spectrum of malignancies associated with common genetic etiology and the effects of gender and age on familial risk have not been established. METHODS: Diagnoses of lymphoproliferative malignancies were compared in 15,799 first-degree relatives of 5047 patients with HL versus 32,117 first-degree relatives of 10,078 control probands from Sweden and in 7185 first-degree relatives of 2429 patients with HL versus 27,434 first-degree relatives of 8,495 control probands from Denmark using marginal survival models. RESULTS: The risk of HL in relatives of patients with HL was increased significantly in both populations, with relative risks of 3.47 (95% confidence interval [95% CI], 1.77-6.80) in Sweden and 2.55 (95% CI, 1.01-6.45) in Denmark and a pooled estimate of 3.11 (95%CI, 1.82-5.29). In Sweden, risks for relatives of patients also were increased significantly for chronic lymphocytic leukemia and non-Hodgkin lymphoma (in males). Relative risks were higher in males compared with females and in siblings of patients compared with parents and offspring of patients. Relatives of patients with earlier-onset disease were at higher risk for HL. CONCLUSIONS: HL has an important familial component, which is stronger in families of affected individuals age < 40 years, in males, and in siblings, and it is shared with some (but not other) lymphoproliferative malignancies. The cumulative lifetime risks are very small, however, for the development of HL de novo or in first-degree relatives of affected patients.     

Risk of second malignant neoplasms among lymphoma patients with a family history of cancer

Radiotherapy and chemotherapy are known risk factors for second cancers after lymphoma. The role of genetic influences, however, remains largely unknown. We assessed risk of second cancers associated with family history of any cancer in 41,181 patients with Hodgkin lymphoma (HL) (n = 7,476), non-Hodgkin lymphoma (NHL) (n = 25,941), or chronic lymphocytic leukemia (CLL) (n = 7,764), using a large population-based database. Family history of cancer was based on a diagnosis of any cancer in 110,862 first-degree relatives. We found increased relative risk (RR) (1.81, 95% confidence interval (CI): 1.04-3.16) of breast cancer among HL patient with positive (vs. negative) family history of cancer. Among CLL patients with positive (vs. negative) family history of cancer, we observed elevated risks of bladder (RR = 3.53, 95% CI: 1.31-9.55) and prostate cancer (RR = 2.15, 95% CI: 1.17-3.94). For NHL patients with positive (vs. negative) family history of cancer, we observed non-significantly increased risk of non-melanoma skin cancer (RR = 1.94, 95% CI: 0.86-4.38) and lung cancer (RR = 1.99, 95% CI: 0.73-5.39). Our observations suggest that genetic factors, as measured by positive family history of cancer, may be influential risk-factors for selected second tumors following lymphoproliferative disorders.     

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.     

Blood transfusions and risk of non-Hodgkin's lymphoma subtypes and chronic lymphocytic leukemia.

Allogeneic blood transfusion has been suggested as a risk factor for non-Hodgkin's lymphoma (NHL), possibly specific to certain NHL subtypes, or chronic lymphocytic leukemia (CLL). Self-reported transfusion history and risk of NHL subtypes and CLL were examined in a cohort of 37,934 older Iowa women, using data from a questionnaire mailed in 1986. Through 1997, 229 cases of NHL and 57 cases of CLL in the cohort were identified through linkage to the Iowa Surveillance, Epidemiology and End Results Cancer REGISTRY: Women who reported ever receiving a blood transfusion were at increased risk for all NHLs [age adjusted relative risk (RR), 1.6; 95% confidence interval (CI), 1.2-2.1). On the basis of the Working Formulation classification, blood transfusion was positively associated with low-grade NHL (RR, 2.7; 95% CI, 1.7-4.5) but not with intermediate-grade NHL (RR, 1.1; 95% CI, 0.7-1.6); there were only 8 cases of high-grade NHL. Blood transfusion was positively associated with follicular (RR, 2.8; 95% CI, 1.6-5.1) and small lymphocytic (RR, 3.4; 95% CI, 1.5-7.9) NHL subtypes but not with diffuse NHL (RR, 1.0; 95% CI, 0.7-1.5). There was also a positive association with CLL (RR, 1.7; 95% CI, 1.0-3.0). Finally, transfusion was associated with nodal (RR, 1.8; 95% CI, 1.3-2.5) but not extranodal (RR, 1.2; 95% CI, 0.7-2.1) NHL. Further adjustment for marital status, farm residence, diabetes, alcohol use, smoking, and red meat and fruit consumption did not alter these associations. In conclusion, prior blood transfusion was associated with NHL and CLL, and the strongest associations were seen for low-grade NHL, particularly follicular and small lymphocytic NHL.     

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.     

Hormone replacement therapy and risk of non-hodgkin lymphoma and chronic lymphocytic leukemia.

Our objective in this study was to evaluate whether the use of hormone replacement therapy (HRT) is associated with non-Hodgkin lymphoma (NHL) or chronic lymphocytic leukemia (CLL). A cohort of 37,220 Iowa women ages 55 to 69 years in 1986 with no history of prior cancer was linked annually to a population-based cancer registry. Through 1998 (13 years of follow-up), 258 incident cases of NHL were identified, including 135 cases of diffuse NHL, 58 cases of follicular NHL, and 31 cases of small lymphocytic NHL. In addition, 63 cases of CLL were identified. Current and former use of HRT (primarily estrogen) and other cancer risk factors were self-reported on the baseline (1986) questionnaire. Compared with never users of HRT at study baseline, current [multivariate relative risk (RR), 1.4; 95% confidence intervals (CIs), 0.9-2.0) but not former (RR, 1.1; 95% CI, 0.8-1.4) users were at increased risk of NHL after adjustment for age and other confounding factors. This association was seen only in nodal NHL [RR(current), 1.5 (95% CI, 1.0-2.4); RR(former), 1.1 (95% CI, 0.8-1.6)] and was not apparent for extra-nodal sites. Of the common subtypes, there was a strong positive association with follicular NHL [RR(current), 3.3 (95% CI, 1.6-6.9); RR(former), 2.6 (95% CI, 1.4-4.7)], and women who were current users for more than 5 years had the highest risk (RR, 3.9; 95% CI, 1.8-8.6). There was no association with diffuse or small lymphocytic NHL, or with CLL. Most of the follicular NHLs were nodal (88%), and exclusion of extra-nodal sites slightly strengthened the association with HRT. For diffuse NHL, 64% of the cases were nodal, and there was no association of HRT with either nodal or extra-nodal sites. These data suggest that HRT is a risk factor for follicular NHL but not for diffuse or small lymphocyte NHL or CLL.     

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.     

Erythrocyte levels of cadmium and lead and risk of B-cell non-Hodgkin lymphoma and multiple myeloma

Cadmium and lead are persistent environmental toxins that are known or probable carcinogens, based on evidence for causality for nonhematologic cancers. Associations of these metals with risk of non-Hodgkin lymphoma (NHL) and multiple myeloma (MM) are unknown but biologically plausible. To examine the associations of circulating levels of lead and cadmium exposure with risk of B-cell NHL (B-NHL) and multiple myeloma, we conducted a nested case-control study among 299 incident B-cell NHLs and 76 MM cases within the Cancer Prevention Study-II Nutrition Cohort (CPS-II NC). Each case was incidence-density matched to two eligible controls on age, race, sex and blood draw date. Conditional logistic regression was used to estimate relative risks (RR) and 95% confidence intervals (CI) for lymphoid malignancies overall and stratified by subtype. We observed a significant positive association between high erythrocyte lead concentration and risk of lymphoid malignancies overall (RR = 1.16, 95% CI: 1.02-1.33 per 17.6 μg/L (1 standard deviation [SD])) and follicular lymphoma in particular (RR = 1.80, 95% CI: 1.15-2.80 per SD). In contrast, there was no association between erythrocyte cadmium and risk of B-NHL (RR = 0.89, 95% CI: 0.75-1.06 per 0.37 μg/L [1 SD]), or any B-NHL subtypes; but a strong inverse association with MM risk (RR = 0.59, 95% CI: 0.38-0.89, per SD). Results from our study suggest a positive association between erythrocyte lead level and risk of lymphoid malignancies and a possible inverse association between cadmium and myeloma. Additional research is needed to confirm and further explore these findings.     

Non-Hodgkin's lymphoma and family history of malignant tumors in a case-control study (United States)

Using data froma case-control study in the United States (the Selected Cancers Study), weexamined the relationship between non-Hodgkin's lymphoma (NHL) and family history of different cancers. Cases were 1,511 men aged 31 to 59 years and diagnosed pathologically with non-Hodgkin's lymphoma during 1984-88. Controls were men, frequency-matched to cases by age range and cancer registry (n = 1,910). All study subjects with acquired immunodeficiency syndrome were excluded from analyses. Our results showed that the risk of NHL is associated with a history of lymphoma (odds ratio [OR] = 3.0, 95 percent confidence interval [CI] = 1.7-5.2) and hematologic cancer (OR = 2.0, CI = 1.2-3.4) in first-degree relatives after adjustment for age, ethnic background, and educational level. Further analyses were performed for the subgroups defined by age at diagnosis (younger than 45 years cf 45 years or older). The association of NHL with a family history of lymphoma and hematologic cancer was found primarily among men aged 45 and older (OR = 4.1, CI = 1.9-8.8 for lymphoma and OR = 2.3, CI = 1.3-4.0 for hematologic cancer). The association among men aged 45 and older did not vary by whether or not there were any familial patients diagnosed at the age of 45 or older. No significant associations could be found for a family history of lung cancer, breast cancer, prostate cancer, colon cancer, skin cancer, liver cancer, stomach cancer, brain cancer, thyroid cancer, or myeloma. This study suggests that the familial risk of NHL is influenced primarily by hematolymphoproliferative malignancies rather than other cancers. The familial effects of hema-tolymphoproliferative malignancies may be stronger for men aged 45 to 59, compared with those aged 31 to 44.     

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.     

Use of non‐steroidal anti‐inflammatory drugs and risk of non‐Hodgkin lymphoma: a systematic review and meta‐analysis

Epidemiological study findings regarding the association between use of non‐steroidal anti‐inflammatory drugs (NSAIDs) and risk of non‐Hodgkin lymphoma (NHL) have been inconsistent. We aimed to systematically review epidemiological studies of the association and calculate pooled relative risks using meta‐analytic methods. We searched eight electronic literature databases and three clinical trial registers to identify all studies (including observational studies and randomized clinical trials) of the association published prior to October 2013. Identified studies were independently reviewed by two researchers. We used a random effects model to calculate pooled odds ratio (PORs). Heterogeneity amongst studies was examined using Cochran's Q and I‐squared (I²) tests; and sources of heterogeneity were explored using subgroup and meta‐regression analyses. A total of 17 studies (12 case‐control studies and five cohort studies), all adult studies, were included. Use of NSAIDs was not associated with overall risk of NHL [POR = 1.05, and 95% confidence interval (95% CI) 0.90–1.22] or NHL subtypes including B‐cell lymphoma, T‐cell lymphoma, follicular lymphoma, diffuse large B‐cell lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Aspirin use was associated with reduced risk of CLL/SLL (POR = 0.70, 95% CI 0.54–0.91) but not with the risk of all NHLs (POR = 1.02, 95% CI 0.89–1.17). Use of non‐aspirin NSAIDs was associated with increased risk of NHL (POR = 1.41, 95% CI 1.01–1.97) amongst females only. The epidemiologic evidence remains inconclusive. Effects of NSAIDs may differ by drug type, NHL subtype, and sex and more studies taking into consideration these differences are needed. Copyright © 2014 John Wiley & Sons, Ltd.     

Alcohol consumption and risk of hematological malignancies: A meta‐analysis of prospective studies

Current convincing evidence suggests that alcohol intake increases the risk of several carcinomas, which might subsequently lead to a recommendation toward limiting alcohol consumption. However, there are accumulating data worth meta‐analyzing that show a different effect on the risk of hematological malignancies. Eligible cohort studies were sought in PubMed database up to August 31, 2016. Separate analyses were performed by subtype of hematological malignancy (non‐Hodgkin lymphoma [NHL] and subtypes, Hodgkin lymphoma [HL], leukemia and subtypes), time status (ever, current, former), level of consumption (light, moderate, heavy), alcoholic beverage (total alcohol, beer, liquor, wine) and gender. Moderate and heavy alcohol consumption were significantly associated with reduced risk of NHL (relative risk [RR] = 0.85, 95% confidence interval [CI]: 0.80–0.90 and RR = 0.73, 95%CI: 0.60–0.89, respectively); a protective trend was also shown for light alcohol intake (RR = 0.93, 95%CI: 0.87–1.00). Specifically, beer consumption was associated with reduced NHL risk (RR = 0.88, 95%CI: 0.81–0.95). However, the association regarding other alcoholic beverages seemed null. The beneficial effects of alcohol mainly pertained to Diffuse Large B‐Cell Lymphoma (DLBCL) (RR = 0.83, 95%CI: 0.77–0.89) and Follicular Lymphoma (FL) (RR = 0.85, 95%CI: 0.78–0.93). There was also no association between alcohol consumption and risk of HL or leukemias. In contrast to most solid malignancies, alcohol seems to confer a protective effect on NHL risk, especially on DLBCL and FL subtypes, with beer being notably beneficial.     

Postmenopausal cancer risk after self-reported endometriosis diagnosis in the Iowa Women's Health Study

BACKGROUND: Endometriosis, the presence of endometrial tissue outside the uterus, has an estimated prevalence between 4% and 10%. A recent study reported that women with a hospital discharge diagnosis of endometriosis were at increased risk of cancer at any site, breast cancer, ovarian cancer, and hematopoietic malignancies, especially non-Hodgkin lymphoma (NHL). METHODS: The authors examined whether self-reported diagnosis of endometriosis was associated with increased risk of various cancers in the Iowa Women's Health Study. Incident cancer cases were identified from 1986 through 1998. Cox proportional hazards regression models were used to calculate relative risks and 95% confidence intervals for the particular cancers of interest. RESULTS: Of 37,434 participants in this analysis, 3.8% reported a history of endometriosis at baseline in 1986. After 13 years of follow-up, 1795 breast, 188 ovarian, and 243 NHL cases were detected in the cohort. Endometriosis was not associated with risk of all cancers combined (age-adjusted relative risk [RR], 0.9; 95% confidence interval [CI], 0.7-1.2), breast carcinoma (RR, 1.0; 95% CI, 0.8-1.3), or ovarian carcinoma (RR, 0.8; 95% CI, 0.2-2.4). However, endometriosis was significantly associated with risk of NHL (age-adjusted RR, 1.8; 95% CI, 1.0-3.0), especially diffuse NHL (RR, 3.2; 95% CI, 1.8-5.6). Multivariate adjustment had minimal effect on the point estimates of risk (NHL RR, 1.7; 95% CI, 0.97-2.7; diffuse NHL RR, 3.3; 95% CI, 1.9-5.9). Endometriosis was not associated with elevated risk of lung, urinary tract, endometrial, melanoma, or colorectal carcinomas (RRs, 1.2, 0.8, 1.2, 0.7, and 0.7, respectively). CONCLUSIONS: These results corroborate a previously reported association between endometriosis and increased risk of NHL but not cancer at other sites.     

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.     

Smoking and risk of non-Hodgkin lymphoma subtypes in a cohort of older women

Although non-Hodgkin lymphoma (NHL) has not been considered to be a smoking-related malignancy, recent investigations suggest otherwise. We evaluated this association in a cohort of 37,336 women, aged 55-69 years, who reported in a mailed questionnaire in 1986 information regarding smoking history as well as demographic, medical history and dietary factors. Cancer and mortality experience through 1996 was determined by linkage to the Iowa Cancer Registry and other databases; there were 200 incident cases of NHL during the 380,231 total person-years of follow-up. Compared to never smokers, former (age-adjusted RR = 1.0; 95% CI 0.8-1.5) and current smokers (age-adjusted RR = 1.0; 95% CI 0.7-1.5) were not at elevated risk of NHL, and there was no trend with pack-years smoked (Ptrend = 0.3). Multivariate adjustment for other NHL risk factors did not alter these findings. Age-adjusted analysis by NHL subtype revealed a suggestive positive association of smoking with follicular NHL [(RRformer = 1.3; 95% CI 0.6-2.8), (RRcurrent = 1.8; 95% CI 0.8-3.8)], which strengthened after multivariate adjustment [(RRformer = 1.6; 95% CI 0.7-3.4), (RRcurrent = 2.3; 95% CI 1.0-5.0)]; there was no association for diffuse or small cleaved-cell NHL. Our study findings, which are consistent with other recent investigations, suggest that smoking may be associated with an increased risk of follicular NHL.     

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.     

Cancer in first-degree relatives and risk of testicular cancer in Denmark

Familial aggregation of testicular cancer has been reported consistently, but it is less clear if there is any association between risk of testicular cancer and other cancers in the family. We conducted a population-based case-control study to examine the relationship between risk of testicular cancer and 22 different cancers in first-degree relatives. We included 3,297 cases of testicular cancer notified to the Danish Cancer Registry between 1991 and 2003. A total of 6,594 matched controls were selected from the Danish Civil Registration System, which also provided the identity of 40,104 first-degree relatives of case and controls. Familial cancer was identified by linkage to the Danish Cancer Registry, and we used conditional logistic regression to analyze whether cancer among first-degree relatives was associated with higher risk of testicular cancer. Rate ratio for testicular cancer was 4.63 (95% CI: 2.41-8.87) when a father, 8.30 (95% CI: 3.81-18.10) when a brother and 5.23 (95% CI: 1.35-20.26) when a son had testicular cancer compared to no familial testicular cancer. Results were similar when analyses were stratified by histologic subtypes of testicular cancer. Familial non-Hodgkin lymphoma and esophageal cancer were associated with testicular cancer; however, these may be chance findings. The familial aggregation of testicular and possibly other cancers may be explained by shared genes and/or shared environmental factors, but the mutual importance of each of these is difficult to determine.     

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.