Non-Hodgkin's lymphoma and hepatitis C virus: a case-control study from northern and southern Italy

HCV has been associated with NHL, but the evidence from case series and case-control studies is not totally consistent. Between 1999 and 2002, we conducted a hospital case-control study on the association between HCV, HBV and NHL in 2 areas of Italy where HCV infection is relatively frequent. Cases (n = 225, median age 59 years) were consecutive patients with a new diagnosis of NHL admitted to local specialized and general hospitals. Controls (n = 504, median age 63 years) were patients with a wide spectrum of acute conditions admitted to the same hospitals as cases. HCV prevalence was 19.6% among NHL cases and 8.9% among controls (adjusted OR = 2.6, 95% CI 1.6-4.3). The ORs for HCV were similar for low-grade and intermediate-/high-grade B-cell NHL (3.2 and 2.4, respectively) as well as for nodal and extranodal NHL (2.7 and 2.6, respectively). Positivity for HBsAg was found in 3.8% of cases and 0.9% of controls (OR = 4.1, 95% CI 1.2-14.4). An elevated OR was also found for history of hepatitis C (OR = 4.7, 95% CI 2.3-9.5). History of blood transfusion before 1990 was associated with HCV positivity among controls but not with NHL risk. In conclusion, HCV infection was associated with an increase in NHL risk, and the fraction of NHL cases attributable to HCV was 12.4% (range 6.3-18.5%).     

Menopausal oestrogens and breast cancer risk: an expanded case-control study

A study among 1960 post-menopausal breast cancer cases and 2258 controls identified through a nation-wide screening program enabled evaluation of effects of oestrogen use on breast cancer risk. Ever use was not associated with increased risk (RR = 1.0), but a significant trend was observed with increasing years of use, with users of 20 or more years being at a 50% excess risk. Elevations associated with long-term use were apparent across all menopause subgroups (natural, ovaries retained, ovaries removed). Hormones exerted particularly adverse effects in those initiating use subsequent to a diagnosis of benign breast disease, particularly long-term users (RR = 3.0, 95% CI 1.6-5.5). There was also some indication that effects predominated among the lower stage tumours, an observation similar to that observed for endometrial cancer. These findings support a role for oestrogens in the aetiology of breast cancer, although risk appears to be enhanced only after extended periods of use, and not to the extent observed for other hormonally-sensitive tumours.     

Oral contraceptives and breast cancer: results from an expanded case-control study

The relationship between oral contraceptives and breast cancer was evaluated among 2,022 cases and 2,183 controls participating in a multicentre breast cancer screening programme. Ever use of oral contraceptives was not related to breast cancer risk (RR = 1.0, 95% CI 0.9-1.2), and no overall patterns of increasing or decreasing risks were observed according to the duration of use, or time since first or most recent use. Although we had no women with extended periods of oral contraceptive use early in life, no evidence of adverse effects attributable to short-term use before age 25, before first live birth or during the perimenopausal period were observed. Further, oral contraceptives did not interact with other breast cancer risk factors, except among those with a history of two or more breast biopsies (RR = 2.0). Analyses by stage of disease revealed that risk was related to the duration of oral contraceptive use: greater than or equal to 5 years use was associated with reduced risk for in situ cancer (RR = 0.59) and increased risks for invasive cancers (RR = 1.5 and 1.4 respectively for small and large lesions). These data suggest that oral contraceptive effects may vary by stage of disease, but provide no overall evidence of an association between oral contraceptives and breast cancer.     

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.     

Non-Hodgkin's lymphoma after kidney transplantation: a single institution study

We treated at our institution six patients with kidney transplantation and lymphoma. After the end of chemotherapy, re-introduction of therapeutic immune suppression was not necessary since, with a significant follow-up (median follow-up of 26 months, range 12-36), no patient had severe renal function deterioration. These preliminary data suggest that, after lymphoma treatment, immune suppression can be withhold at least for 2 years. Restoration of a functional immune system may contribute to decrease the rate of lymphoma recurrence, in line with the absence of lymphoma relapse in our six patients, who are all still alive and in complete remission.     

Non-Hodgkin's lymphoma: an analysis of the Metropolitan Detroit SEER database

We evaluated incidence and survival trends of non-Hodgkin's lymphoma (NHL) in a large population-based cancer registry. Data regarding demographics, histology, incidence, and survival were obtained on all patients with NHL registered in the Metropolitan Detroit Cancer Surveillance System, a participant in the Surveillance Epidemiology and End Results (SEER) Program of the National Cancer Institute. Incidence and survival trends from 1973 through 1995 were evaluated and stratified based on age at diagnosis, sex, race, and tumor grade. There were 11,978 patients diagnosed with NHL and recorded in the Metropolitan Detroit SEER registry from 1973 to 1995. The age-adjusted incidence rate increased from 8.6 to 15.8 per 100,000, leading to an overall increase in incidence of 83% and an average annual increase of 3.2% per year. Incidence increased significantly (p < 0.05) over time in all age groups except the youngest (ages 0-19) and in all demographic groups studied. Incidence was highest in white men and lowest in black women. The incidence of both low-grade and intermediate/high-grade NHL increased significantly for each age group (p < 0.05) except the youngest (ages 0-19). In the oldest patients (70+ years), the incidence of intermediate/high-grade NHL was almost double that of low-grade NHL. Five-year relative survival increased from 64% (1973-1983) to 68% (1984-1991) for patients with low-grade NHL and from 40% to 44% for those with intermediate/high-grade NHL. The increase in relative survival was only seen in whites, however, with 5-year relative survival in blacks decreased from 53% (1973-1983) to 45% (1984-1991). In metropolitan Detroit, the current NHL epidemic affects all age groups except the very young (ages 0-19), both sexes, and both whites and blacks and is due to increases in the incidence of both low-grade and intermediate/high-grade NHL. Five-year survival rates have increased for whites but not for blacks.     

Smoking and non-Hodgkin lymphoma: case-control study in Italy

Tobacco smoking is a well-documented risk factor for several cancers, but the role of cigarette smoking in the etiology of non-Hodgkin lymphoma (NHL) is inadequately understood. Hepatitis C virus (HCV) has been associated with NHL, but the interaction between HCV and smoking habits has not yet been studied. Between 1999 and 2002, we conducted a case-control study on the association of HCV, smoking habits and NHL in 2 areas of northern and southern Italy. Cases were 225 consecutive patients (median age, 59 years) with a new diagnosis of NHL that were admitted to reference and general hospitals. Controls were 504 patients (median age, 63 years) admitted to the same hospitals as cases, for a wide spectrum of acute, nonneoplastic, nonimmune-, nor tobacco-related conditions. Current, heavy smokers (> or = 20 cigarettes/day) had an odds ratio (OR) of NHL of 2.10 (95% confidence interval, CI: 1.07-4.12) compared to never smokers. The association between smoking and NHL was consistent across strata of sex and age. Compared to never smokers, current smokers of > or = 20 cigarettes/day had ORs of 1.14 (95% CI: 0.37-3.56) for B-cell-low-grade, 2.10 (95% CI: 0.94-4.67) for B-cell-intermediate and high-grade, and 25.84 (95% CI: 1.95-342.17) for T-cell NHL. The effect of tobacco smoking and HCV were independent on the relative risk, leading a 4-fold elevated risk in current smokers HCV positive subjects. Tobacco smoking and hepatitis C virus (HCV) have been associated to non-Hodgkin lymphoma (NHL), but the interaction between HCV and smoking habits has not yet been studied. Our study confirms that tobacco is related to NHL, and reports on the combined effect of tobacco smoking and HCV. Infection acted together according to a multiplicative model, leading to a 4-fold elevated risk in current smokers HCV positive subjects.     

Non-Hodgkin's lymphoma in pregnancy

Non-Hodgkin's lymphoma associated with pregnancy is rare. To date, only 1 case in which lymphoma was diagnosed and treated during pregnancy, with normal pregnancy outcome, has been reported. We describe another case where life-threatening, diffuse, poorly differentiated lymphocytic lymphoma was diagnosed during the 13th week of pregnancy. Combination chemotherapy (cyclophosphamide, vincristine, bleomycin, and prednisone) resulted in remission and a health full-term infant was born.     

Non-Hodgkin's lymphoma: the old and the new

During the past decade we have witnessed a number of changes in the field of non-Hodgkin lymphoma (NHL), including new entities added to the classification as well as a better understanding of the biology of diffuse large B-cell lymphoma (DLBCL). An understanding of the epigenetics of NHL is also contributing new agents for the management of this disorder. It has become increasingly clear that DLBCL is a biologically and clinically heterogeneous cell type. Two major categories are now recognized: germinal center B cell and activated B-cell (ABC) types. The former is associated with a good prognosis while the latter is known to have a more adverse outcome. With the use of routine immunohistochemical stains, these two types can be identified. The ABC type is known to be NFK-B dependent. NFK-B is a therapeutic target for bortezomib which is being investigated as treatment for this subtype of DLBCL. Several major changes in the classification will be discussed among which the most important are the recognition of so-called borderline entities. One of the two most common of these is the borderline DLBCL/Burkitt tumor (DLBCL/BL) which has features of both DLBCL and Burkitt's lymphoma. Many of the cases in this DLBCL/BL category contain a translocation of MYC as well as BCL2, so-called "double-hit lymphomas" which have a very aggressive clinical behavior. The second common borderline entity is the mediastinal grey zone NHL (MGZL) which has pathological features intermediate between primary mediastinal B-cell lymphoma and nodular sclerosing Hodgkin lymphoma (NSHL). Overlapping clinical features include young age, male predominance, and localized mediastinal presentation. Anecdotal reports suggest MGZL is relatively resistant to Hodgkin-based chemotherapy. Epigenetic therapy represents a new concept. Histone deacetylase inhibitors (HDACi)and DNA methyltransferase inhibitors constitute a promising new class of antineoplastic agents. They modify the expression of genes related to cancer development. In this review, we discuss the role of HDACi in lymphomagenesis as well as in treatment. To understand the benefits of HDACi in lymphoma treatment, we must appreciate the crucial interplay between BCL6, p53, and STAT3. The STAT3 oncogene is involved in the ABC type of DLBCL, an unfavorable and frequently therapy-refractory lymphoma. STAT3 can be effectively suppressed by several HDACi. We will summarize the results of recent trials with HDACi such as romidepsin, panobinostat and valproic acid that have shown significant preliminary activity in recurrent and refractory lymphomas. Their future role in front-line management remains to be determined.     

Farming and mortality from non-Hodgkin's lymphoma: A case-control study

A case-control study of non-Hodgkin's lymphoma (NHL) and its subtypes among males was conducted using computerized mortality listings from the State of Wisconsin for the years 1968-1976. Age, year of death, race, county of usual residence, marital status, and usual occupation were abstracted for the 774 records of male deaths due to NHL and a matched series of deaths due to other causes. The frequency of farming occupation among NHL cases was compared to the frequency among controls, and odds ratios (OR) were calculated. Farming was more common among cases than among controls (OR=1.22). The association of NHL with farming occupation was greater among decedents under 65 years of age (ORequlas;1.7) than among those who were older. The younger decedents were at higher risk of reticulum-cell sarcoma (ORequlas;2.7) than of other cell types. The strength of the association increased over the 9-year study period. County levels of selected agricultural characteristics were used as surrogate measures of farming exposures in residence counties of farmers and were summarized by factor analysis. Major findings were of elevated risk among younger farmers for reticulum-cell sarcoma in counties high in summary measures of general agricultural activity (ORequlas;3.2), of small grain acreage and acres treated with insecticides (ORequlas;6.6), and of wheat acreage (ORequlas;4.4). Given the limitations of the data, further investigation of non-Hodgkin's lymphoma in farmers is warranted.     

Non-Hodgkin's lymphoma in children.

Until recently the prognosis of childhood non-Hodgkin's lymphoma has been poor. A program of combination chemotherapy and involved area radiotherapy was instituted in the Department of Pediatrics at Roswell Park Memorial Institute in 1971. Thirty-one biopsy proven untreated children entered this study. There were 4 Stage I, 9 Stage II, 6 Stage III, and 12 Stage IV. Initial site of presentation was neck and mediastinum in 16, abdomen in 12, and other sites in three. Nineteen were lymphocytic, seven histiocytic, three undifferentiated, and one was mixed. None had well differentiated or nodular histology. Chemotherapy consisted of vincristine and steroid induction along with intrathecal methotrexate followed by a maintenance phase consisting of daily oral 6-mercaptopurine, weekly oral methotrexate and monthly pulses of vincristine, cyclophosphamide and steroid. Because of initially poor results in Stage IV disease, the protocol was altered midway and high dose methotrexate on three occasions following induction was added. Twelve of 13 Stage I and II patients remain disease free. Four of 6 Stage III patients and 4 of 12 Stage IV patients remain disease free. Only 1/7 of the Stage IV patients prior to high dose methotrexate is disease free, whereas, 3/5 patients with high dose methotrexate are disease free. In total, 19/30 (63%) are disease free for a period ranging from 15+ to 63+ months with 19 patients being disease free for over one year and 12 for over two years.     

Non-Hodgkin's lymphoma of Waldeyer's ring

The authors retrospectively analyzed 103 patients to investigate the value of examination of Waldeyer's ring with biopsies as a staging procedure in patients with non-Hodgkin's lymphoma. Twenty-three patients had clinical involvement of Waldeyer's ring. In 55 of 80 remaining patients, this staging procedure was performed but positive biopsy specimens were found only in patients with advanced disease. No correlation was found between positive biopsy specimens and the histologic subtype. No positive biopsy specimens of Waldeyer's ring were obtained in patients with cervical lymphadenopathy without clinical involvement of the nasopharynx and in patients with localized lymphoma of the gastrointestinal tract. Blind biopsies of Waldeyer's ring as a staging procedure proved to be of no value in the patients. The results of therapy in 23 patients with involvement of Waldeyer's ring were good. Unfavorable histologic subtypes (intermediate or high-grade malignancy) were predominant (91%). Eighteen of 22 patients (82%) achieved complete remission, with a relapse-free survival rate at 60 months of 95%. For the whole group of patients, the actuarial survival rate at 72 months was 71%.     

Sun exposure and non-Hodgkin lymphoma: a population-based, case-control study

To investigate the association between sun exposure and risk of non-Hodgkin lymphoma (NHL) by histologic subtypes and to explore whether or not vitamin D intake modify sun-NHL association, we analysed data from a population-based, case-control study conducted in Nebraska between 1999 and 2002. Information on sun exposure during the spring, summer, fall and winter was collected from 387 cases and 535 controls by telephone interview. We found no association between seasonal sun exposure and risk of NHL. Vitamin D intake was also not associated with NHL risk, nor does it modify the sun-NHL association. In contrast, total hours of sun exposure was inversely associated with the risk of NHL (odds ratio (OR)=0.7 comparing >30h/week to <14h/week, 95% confidence interval (CI)=0.5-1.1). Sun exposure was associated with a lower risk of NHL among farmers (OR=0.8, 0.5-1.3 for 14-30h/week; OR=0.6, 0.3-0.9 for >30h/week; p-trend=0.02), but not among non-farmers. Total hours of sun exposure was also inversely associated with risk of diffuse large B-cell lymphoma and T-cell lymphoma. In conclusion, our data suggest that total hours of sun exposure is associated with a lower risk of NHL, and the inverse association is not modified by vitamin D intake, is stronger among farmer, and may vary by subtypes.