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.     

Soft-tissue sarcoma, non-Hodgkin's lymphoma and other cancers in New Zealand forestry workers

Several studies have suggested that forestry workers are at increased risk for certain types of cancer including soft-tissue sarcoma (STS) and non-Hodgkin's lymphoma (NHL). We now report a series of national case-control studies based on the New Zealand Cancer Registry (NZCR). These involved 19,904 male patients with cancer for the period 1980-1984 who were aged 20 years or more at the time of registration. For each cancer site, the registrations for the remaining sites formed the control group. Current or most recent occupational titles were coded. There was an increased risk for STS (OR = 3.24) in forestry workers which was confined to men under 60 years of age at registration. An elevation in risk for NHL (OR = 1.84) was due to an increase in risk for lymphosarcoma and reticulosarcoma (ICD 200) (OR = 3.18). Acute myeloid leukemia was also associated with forestry work, although the estimate of risk was imprecise (OR = 2.24). Among other cancer sites, an increase in risk of neoplasia of the upper gastro-intestinal tract (ICD 150, 151, 152) was demonstrated. Odds ratios were elevated for cancer of the esophagus (OR = 1.77), stomach (OR = 2.22), small intestine (OR = 5.22), gall-bladder (OR = 4.13) and pancreas (OR = 1.79), as well as for nasopharyngeal cancer (OR = 5.56). These increases in cancer risk were not present in sawmill workers in New Zealand during the same period. The factors responsible for the increased cancer risks in forestry workers remain unclear and require further study.     

Second cancers following non-Hodgkin's lymphoma

The risk of second malignancies following non-Hodgkin's lymphoma (NHL) was estimated in 29,153 patients diagnosed with NHL between 1973 and 1987 in one of nine areas participating in the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. Compared with the general population, NHL patients were at a significantly increased risk of developing second cancers (observed/expected [O/E] = 1.18; O = 1231). The O/E ratio increased significantly with time to reach 1.77 in 10-year survivors. Significant excesses were noted for acute nonlymphocytic leukemia (O/E = 2.88), cancers of the bladder (O/E = 1.30), kidney (O/E = 1.47), and lung (O/E = 1.57), malignant melanoma (O/E = 2.44), and Hodgkin's disease (O/E = 4.16). Chemotherapy appeared related to subsequent acute nonlymphocytic leukemia (ANLL) and bladder cancer. Radiation therapy was associated with ANLL and possibly cancers of the lung, bladder, and bone. Malignant melanoma was not clearly related to initial NHL treatment.     

Comprehensive lymphatic irradiation for stage II-III non-Hodgkin's lymphoma

Thirteen patients with stage II-III non-Hodgkin's lymphoma (NHL) and one patient with minimal marrow involvement were selected for treatment between 1964 and 1986 with moderate-dose comprehensive lymphatic irradiation (CLI). This approach has been well tolerated and has produced relapse-free and overall survival rates at 10 years of 60 and 66%, respectively. Salvage therapy for failure following CLI has been possible. CLI produces results comparable to any achieved with combined modality therapy, offers less acute and late toxicity, and requires only 3-4 months for completion.     

Risk of non-Hodgkin's lymphoma following tuberculosis

To study the association between chronic infections and non-Hodgkin's lymphoma (NHL), we assessed the risk of NHL in a Swedish cohort of 5050 individuals with tuberculosis 1939-1960. The overall relative risk was moderately increased, largely accounted for by high risks following severe tuberculosis diagnosed a long time ago.     

Clinical significance of hematologic parameters in non-Hodgkin's lymphoma at diagnosis

Three hundred seventeen patients with non-Hodgkin's lymphoma (NHL) (54 low grade, 180 intermediate grade, 76 high grade, and seven unclassified) treated with chemotherapy were evaluated for the presence of hematologic abnormalities at diagnostic staging. Anemia was present in 42%, leukopenia in 6%, thrombocytopenia in 13%, leukocytosis in 26%, and thrombocytosis in 14% at presentation. The presence of bone marrow involvement by lymphoma was more likely to be associated with leukopenia and thrombocytopenia than the absence of bone marrow involvement. Although anemia was slightly more common in patients with bone marrow lymphoma than in those without marrow lymphoma, the difference was not statistically significant. Hematologic parameters were similar for patients with B-cell or T-cell lymphoma. Evidence of bone marrow failure with multiple cytopenias was present in 26 patients (8%). Leukoerythroblastosis was present in 2%. Circulating lymphoma was present in 9.5%. Anemic patients had a shorter survival time than nonanemic patients, whether bone marrow was involved by lymphoma or not. Survival was not affected by the presence of leukopenia or mild leukocytosis, but, in patients without marrow lymphoma, leukocytosis with a leukocyte count greater than 20 x 10(9)/l was associated with short survival length. Thrombocytopenia was associated with short survival time only in patients with bone marrow involvement by lymphoma. Patients with multiple cytopenias or leukoerythroblastosis had short survival times, but the presence of circulating lymphoma did not alter survival when compared with other patients with bone marrow involvement by lymphoma. These data suggest that hematologic evaluation at the time of diagnostic staging of NHL provides useful prognostic information that may have therapeutic implications.     

SV40 in human brain cancers and non-Hodgkin's lymphoma

Simian virus 40 (SV40) is a potent DNA tumor virus that is known to induce primary brain cancers and lymphomas in laboratory animals. SV40 oncogenesis is mediated by the viral large tumor antigen (T-ag), which inactivates the tumor-suppressor proteins p53 and pRb family members. During the last decade, independent studies using different molecular biology techniques have shown the presence of SV40 DNA, T-ag, or other viral markers in primary human brain cancers, and a systematic assessment of the data indicates that the virus is significantly associated with this group of human tumors. In addition, recent large independent studies showed that SV40 T-ag DNA is significantly associated with human non-Hodgkin's lymphoma (NHL). Although the prevalence of SV40 infections in humans is not known, numerous observations suggest that SV40 is a pathogen in the human population today. This review examines the molecular biology, pathology, and clinical data implicating SV40 in the pathogenesis of primary human brain cancers and NHL and discusses future research directions needed to define a possible etiologic role for SV40 in these malignancies.     

Familial cancers associated with subtypes of leukemia and non-Hodgkin's lymphoma

To investigate whether a history of hematolymphoproliferative cancers (HLP) and other cancers among a parent or sibling is a risk factor for specific subtypes of leukemia and non-Hodgkin's lymphoma (NHL), data from a population-based case-control study, in Iowa and Minnesota, of 578 leukemia cases, 622 NHL cases and 1245 controls were evaluated. Having at least one sibling with HLP significantly increased the risk for all leukemias combined (odds ratio (OR) = 2.3) and for NHL (OR = 2.7). In particular, chronic lymphocytic leukemia (CLL) was significantly increased among those reporting a sibling with leukemia (OR = 3.0) or lymphoma (OR = 4.3). Elevated risks of small lymphocytic NHL (SML) (OR = 7.3) and diffuse NHL (DIF) (OR = 5.4) were also observed among subjects who had a sibling with lymphoma (primarily Hodgkin's disease). A significantly increased risk of follicular NHL was noted among those with a sibling history of pancreatic cancer (OR = 4.8) and colorectal cancer (OR = 2.7). Parental history of HLP was not associated with any type of leukemia or NHL. A history of stomach cancer among parents was associated with a 2-fold elevation of CLL and DIF compared to controls. Increased risks of CLL and DIF were also linked to breast cancer among sisters and mothers, respectively. Prostate cancer among fathers increased the risk 2-fold for CLL and 3-fold for SML. This study confirms some familial cancer associations previously reported for leukemia and NHL, and provides new information regarding the various subtypes of leukemia and NHL.     

Natural history of follicular grade 3 non-Hodgkin's lymphoma

PURPOSE OF REVIEW: Follicular lymphoma grade 3 is recognized as a distinct entity in the World Health Organization classification of lymphomas. There is confusion regarding the natural history of these lymphomas, because some studies indicate an indolent behavior and others show more aggressive behavior. This review examines the biological and clinical characteristics of follicular lymphoma grade 3 and compares these characteristics with other lymphomas. RECENT FINDINGS: Several reports suggest that follicular lymphoma grade 3 has molecular and genetic characteristics that distinguish these lymphomas from other grades of follicular lymphoma. These characteristics are often more common in patients with diffuse large B-cell lymphoma than follicular lymphoma. It is impossible to make firm recommendations on management because prospective trials are lacking. Nevertheless, recent studies have demonstrated that follicular lymphoma grade 3 patients treated with anthracycline-based therapy have similar outcomes to patients with diffuse large B-cell lymphoma. SUMMARY: Patients with follicular lymphoma grade 3 should be treated with curative intent. They should receive aggressive anthracycline-based therapy combined with rituximab, which is identical to therapy used for patients with diffuse large B-cell lymphoma.     

Risk of subsequent cancers in renal cell carcinoma survivors with a family history

BackgroundThis study aimed at elucidating the effect of family history on the development of subsequent cancers in renal cell carcinoma (RCC) survivors and aimed at assessing whether the interactions between risks of subsequent cancers in RCC survivors and familial risk of subsequent cancer are additive or multiplicative interactions.MethodsA population-based cohort (Swedish Family-Cancer Database) of 14,267 RCC patients diagnosed in 1990–2010 was followed for cancer incidence. Standardised incidence ratios (SIRs) were calculated for subsequent cancers in RCC survivors and in RCC survivors with a family history of subsequent cancer. Familial risk of subsequent cancer was calculated for individuals with family history of specific cancer, compared to those without.ResultsFor subsequent hemangioblastoma (HB) in RCC survivors, drastically elevated risk was observed for the effect of family history of HB [SIR = 777 (95% confidence interval (CI): 160–2270)] and of family history of RCC [378 (46–1367)]. Colorectal, lung, prostate and RCCs favoured additive interactions between risk of subsequent cancers in RCC survivors and familial risk, while endocrine glands, nervous system and urinary bladder cancers favoured multiplicative interactions.ConclusionsRisks of subsequent HB in RCC survivors were tremendously modified by family history of RCC or HB, which may resemble characteristics of von Hippel–Lindau syndrome and show the power of present approach to detect heritable cancer clusters. Additive or multiplicative interactions found for colorectal, lung, prostate, endocrine glands, nervous system, urinary bladder and RCCs might raise awareness among clinicians and RCC survivors with a family history of seven cancers about elevated risks of subsequent those cancers.     

Second primary cancers among 109 000 cases of non-Hodgkin's lymphoma

An analysis of other primary cancers in individuals with non-Hodgkin's lymphoma (NHL) can help to elucidate this cancer aetiology. In all, 109 451 first primary NHL were included in a pooled analysis of 13 cancer registries. The observed numbers of second cancers were compared to the expected numbers derived from the age-, sex-, calendar period- and registry-specific incidence rates. We also calculated the standardised incidence ratios for NHL as a second primary after other cancers. There was a 47% (95% confidence interval 43-51%) overall increase in the risk of a primary cancer after NHL. A strongly significant (P<0.001) increase was observed for cancers of the lip, tongue, oropharynx*, stomach, small intestine, colon*, liver, nasal cavity*, lung, soft tissues*, skin melanoma*, nonmelanoma skin*, bladder*, kidney*, thyroid*, Hodgkin's lymphoma*, lymphoid leukaemia* and myeloid leukaemia. Non-Hodgkin's lymphoma as a second primary was increased after cancers marked with an asterisk. Patterns of risk indicate a treatment effect for lung, bladder, stomach, Hodgkin's lymphoma and myeloid leukaemia. Common risk factors may be involved for cancers of the lung, bladder, nasal cavity and for soft tissues, such as pesticides. Bidirectional effects for several cancer sites of potential viral origin argue strongly for a role for immune suppression in NHL.     

Asthma history, occupational exposure to pesticides and the risk of non-Hodgkin's lymphoma

We previously reported that, although asthma did not increase the risk of non-Hodgkin's lymphoma (NHL), the risk from pesticide exposures was higher among asthmatics than that among nonasthmatics. To further evaluate this finding, we analyzed data from a population-based case-control study of NHL conducted in Iowa, Detroit, Los Angeles and Seattle. Cases (n = 668) diagnosed with NHL from 1998 to 2000 and controls (n = 543) randomly selected from the same geographical areas as that of the cases were included in this analysis. Odds ratios (OR) for the risk of NHL from potential occupational exposure to pesticides tended to be higher among asthmatics (OR = 1.7; 95% CI 0.3-9.1) when compared with that among nonasthmatics (OR = 0.9; 95% CI 0.6-1.5). The risks of NHL associated with pesticide exposure were also higher among asthmatics who had history of hospitalization (OR = 2.1; 95% CI 0.2-29.0) or daily medication for asthma (OR = infinite) than those among asthmatics who did not have such histories. Our results support the previous finding that the risk of NHL from pesticide exposure may be greater among asthmatics.     

Advances in the epidemiology of HIV-associated non-Hodgkin's lymphoma and other lymphoid neoplasms.

The spectrum of HIV-related lymphoid malignancies certainly includes non-Hodgkin's lymphoma (NHL; i.e., chiefly large-cell lymphoma and Burkitt's lymphoma), primary lymphoma of the brain (PBL) and, possibly, Hodgkin's disease (HD). Since the mid-1990s, several epidemiological studies have led to better quantification of the burden of lymphomas in HIV-infected populations. AIDS surveillance data from 17 western European countries show that between 1988 and 1997 a total of 7,148 AIDS cases had NHL as the AIDS-defining illness. The yearly number of cases rose steadily from 1988 to 1995 but declined thereafter. As a percentage of AIDS-defining illnesses, NHL increased from 3.6% in 1994 to 4.9% in 1997. Percent increases were observed in different strata by area, age group, sex and HIV-transmission group. To estimate relative risk (RR) of NHL and other lymphoid neoplasms in unselected HIV-seropositive populations, records of population-based cancer registries and AIDS registries were linked in the United States, Italy and Australia. RRs for NHL in adults with HIV/AIDS ranged between 14 (for low-grade NHL) to over 300 (for high-grade NHL). For HD, the RR was approximately 10. Limited findings from studies based on death certificates and cohorts of HIV-seropositive persons were consistent with those from registry linkage studies. In developing countries, the risk of HIV-associated NHL appears to be much lower than in developed countries, but under-ascertainment and earlier death from other AIDS manifestations may explain the lack of HIV-associated lymphomas in Africa.     

Risk of non-Hodgkin's lymphoma and skin malignancies in patients diagnosed with cataract.

The rapid increase of non-Hodgkin's lymphoma (NHL) in industrialized countries is yet unexplained. Ultraviolet radiation (UVR) has been suggested as an aetiologic factor due to observed elevated risks of cutaneous malignancies after NHL and vice versa. Cataract, as related to UVR, was tested as a proxy variable to further elucidate this observation. Cataract in-patients (n = 49914) reported to the Swedish Patient Register and later developing NHL and cutaneous malignancies were identified by record linkage to the Swedish Cancer Registry. The observed number of malignancies among cataract patients did not differ significantly from that expected in the general population. In contrast, the risk of cutaneous malignant melanoma was lower than anticipated, based on Swedish background incidence figures. The results did not give support for a causal relationship between NHL and UVR.     

Risk perception, family history, and use of breast cancer screening tests.

A family history of breast cancer is an established risk factor for the disease, but there are few published studies on the use of breast cancer screening tests among family-history-positive women. Among 1015 respondents to telephone surveys of random samples of women 50 to 75 years old residing on Long Island (New York), the frequency of ever having had a mammogram or having a mammogram during the past year was significantly higher in respondents with a self-reported family history of breast cancer than in other women 50 to 64 (but not 65 to 75) years old. The association between family history and mammography during the past year held only among 50 to 64-year-old women with a lower perceived risk of breast cancer. Among women 50 to 64 years old, strong agreement with the ability of mammography to detect nonpalpable lumps was positively associated with mammography during the past year, especially among women with lower perceived risk of breast cancer. Implications are discussed with regard to breast cancer screening programs.     

Risk of non-Hodgkin's lymphoma and exposure to hexachlorocyclohexane, a nested case-control study

Organochlorines have been linked with non-Hodgkin's lymphoma (NHL) in epidemiological studies. We elucidate the importance of hexachlorocyclohexane (HCH), an organochlorine insecticide, in the aetiology of NHL among individuals with dermal exposure to HCH. This is a case-control study nested in a cohort of sheep owners, collected from records on sheep dipping. The number of dipped sheep was used as surrogate for exposure. No other insecticide was used in sheep dip in Iceland during the study period. Cases (n=45) were identified by record linkage with the national cancer registry (through 1962-2003) and controls (n=221) were selected at random from the cohort. In logistic regression analysis the odds ratio for NHL was 3.86 (95% CI 1.59-8.53), adjusted for age, for individuals who had 100 sheep or more as compared to those who had less than 100 sheep. The results indicate that HCH may be linked to the development of NHL.     

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.     

Treatment of non-Hodgkin's lymphoma.

Many of the advances in the management of non-Hodgkin's lymphomas have been based on more precise understanding of the various cell types that constitute these disorders. During the past year, we have seen some dramatic changes in the therapeutic approach to low-grade lymphomas. Until recently, the usual approach to these disorders was a purely palliative one, but a number of publications from the past year describe a more intensive approach with the goal of developing a curative modality. The use of combination chemotherapy in addition to radiation therapy for the early Ann Arbor stages as well as the use of high-dose chemotherapy with bone marrow transplantation in patients with high-risk factors has been reported recently. In the area of intermediate-grade lymphomas, most of the recent publications have described prognostic factors associated with various chemotherapy protocols. One of the most interesting recent developments is related to the dose-intensity issue. A consensus appears to be developing in regard to the correlation of dose intensity with clinical outcome. Despite the fact that new third-generation regimens have been associated with cures in 50% to 66% of the patients, a significant fraction of patients require salvage chemotherapy. Some of the new salvage regimens are discussed, as is the use of calcium channel blockers to reverse multiple-drug resistance. Finally, management of the high-grade lymphomas, specifically the small noncleaved cell type, has been associated with a cure rate in the range of 50% in two recently published studies. Patients who are human immunodeficiency virus-positive with small noncleaved cell lymphoma can be cured of their underlying malignancy, but many of them later develop complications of acquired immunodeficiency syndrome, to which they usually succumb.     

Chemotherapy for non-Hodgkin's lymphoma.

The term non-Hodgkin's lymphoma (NHL) refers to a diverse group of illnesses that have in common a high frequency of chemotherapy sensitivity. In fact, high-grade NHL was among the first cancers to be cured with chemotherapy. Although the curability of patients with low-grade NHL remains debatable, all patients with intermediate- and high-grade NHL should be approached with curative intent, even if they present with advanced disease. Our ability to treat patients with NHL is steadily improving. There have been significant advances in our understanding of the biology of the disease and our ability to predict treatment outcome. New treatments and innovative uses of already available treatments are regularly reported. This paper reviews the highlights of the past year's literature regarding the treatment of patients with NHL.