Comorbidities, therapy, and newly diagnosed conditions for women with early stage breast cancer

Purpose  To describe comorbidities in breast cancer patients at diagnosis and examine factors associated with self-reported comorbidities 30 months post-diagnosis. Methods  Nine hundred forty one of 1,171 women had a medical record abstract and a follow-up survey in the Health, Eating, Activity and Lifestyle Study. Results  We compared our breast cancer cohort to a contemporaneous nationally-representative sample of age, race/ethnicity and education matched women without cancer (n = 865). Breast cancer patients did not have substantially more comorbidities than women without breast cancer. Women with a hospital record of congestive heart failure significantly less often received chemotherapy or radiation following breast conserving surgery. In multivariate analysis, women who received chemotherapy alone (OR = 3.2; 95% CI: 1.5–6.8), chemotherapy plus radiation (OR = 1.9; 95% CI: 1.02–3.7) or radiation plus tamoxifen (OR = 1.9; 95% CI: 1.1–3.2) were significantly more likely to report at least one new comorbid condition following breast cancer diagnosis than women who received no chemotherapy, tamoxifen or radiation. Overall, women who received adjuvant therapy were more likely to have new comorbidities. Conclusions  Comorbidities were not substantially different in breast cancer patients than the non-cancer matched controls. Future research should focus on efforts to minimize comorbidities related to chemotherapy and other combination therapy. Funding source  N01-PC-35139, N01-PC-35142, N01-PC-35138     

Sunlight exposure,vitamin D,and risk of non-Hodgkin lymphoma in the Nurses’ Health Study

Purpose  

Case–control studies suggest increased sun exposure reduces non-Hodgkin lymphoma (NHL) risk. Evidence from prospective cohort studies, however, is limited and inconsistent. We evaluated the association between ambient ultraviolet radiation (UV) exposure and NHL in a nationwide cohort of women, the Nurses’ Health Study (NHS).     

Association of aspirin and other non-steroidal anti-inflammatory drug use with incidence of non-Hodgkin lymphoma

Non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin, seem to have chemopreventive properties against several types of cancer, particularly colon cancer. Persons with rheumatoid arthritis, an autoimmune disease for which NSAIDs are used commonly, have been reported to be at lower risk of colon cancer but at elevated risk of non-Hodgkin lymphoma (NHL), raising the possibility that NSAIDs may be a risk factor for NHL. We evaluated the association of use of NSAIDs, arthritis history, and risk of NHL in a prospective cohort of 27,290 postmenopausal women from the state of Iowa. The frequency of use of aspirin and of other NSAIDs excluding aspirin (e.g., ibuprofen), as well as a physician diagnosis of rheumatoid arthritis (RA) or osteoarthritis (OA), were self-reported on a questionnaire mailed in 1992. The incidence of NHL was ascertained through annual linkages to the Iowa SEER Cancer Registry. Relative risks (RR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards regression. Through 7 years of follow-up, 131 cases of NHL were identified. Compared to women who did not use either aspirin or other non-aspirin NSAIDs, women using aspirin exclusively (RR = 1.71; 95% CI = 0.94-3.13), non-aspirin NSAIDs exclusively (RR = 2.39; 95% CI = 1.18-4.83), or both types of drugs (RR = 1.97; 95% CI = 1.06-3.68) were at increased risk of NHL. A diagnosis of RA (RR = 1.75; 95% CI = 1.09-2.79), but not OA (RR = 1.06; 95% CI = 0.67-1.68), was associated with risk of NHL, but the positive association of use of aspirin and other NSAIDs with NHL was independent of RA history. Multivariate adjustment for other NHL risk factors only attenuated slightly these associations, whereas exclusion of cases occurring during the first 2 years of follow-up strengthened the associations. These data suggest that use of NSAIDs, either aspirin or other non-aspirin NSAIDs, are associated positively with risk of NHL, and that this association is independent of RA history.     

Estimated Urine pH and Bladder Cancer Risk in a Cohort of Male Smokers (Finland)*

Objective:Low urine pH may be an important risk factor for bladder cancer, although few studies have evaluated this association. We examined the relationship between estimated renal net acid excretion (NAE), an indirect measure of urine pH based on nutrient intake and anthropometry, and bladder cancer risk in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. Methods: At baseline, 27,096 male smokers 50–69 years old completed a dietary questionnaire that assessed usual frequency of consumption and portion sizes for the previous 12 months, had height and weight measured, and provided a history of smoking. A total of 446 incident bladder cancer cases were identified during up to 17.4 years of follow-up. Results: In multivariate proportional hazards models, the relative risk (RR) for bladder cancer was 1.15 (95% confidence interval (CI)=0.86–1.55) for individuals in the highest (i.e., most acidic) versus the lowest (i.e., least acidic) NAE quintile (p=0.38). Among men who smoked for more than 45 years, there was a suggestion of increased risk with higher NAE levels (RR=1.72, 95% CI=0.96–3.10, p=0.08). Conclusions: These findings do not indicate that urine pH is a major risk factor for bladder cancer, although certain subsets of individuals may be at increased risk. Supported by US Public Health Service contract N01CN45165 and N01CN45035 from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services.     

Sun exposure, vitamin D receptor gene polymorphisms and risk of non-Hodgkin lymphoma

Objective Recent findings suggest that ultraviolet (UV) radiation exposure may reduce risk of developing non-Hodgkin lymphoma (NHL), but the biologic basis for this relationship remains unclear. We analyzed data from our US population-based case–control study of NHL to investigate whether our previously reported inverse association with sun exposure was dependent upon variants in the vitamin D receptor gene (IVS10 + 283G > A (BsmI), Ex11 + 32T > C (TaqI)), and genes linked to UV-induced immune modulation (IL4, IL10, IL12A, IL12B, TNF). Methods UV exposure data was collected from an in-person interview with 551 cases and 462 controls. We calculated odds ratios (OR) and 95% confidence intervals (CI) for sun exposure measures for joint variant-exposure effects. Results The association with NHL risk for time in the midday sun within the last decade was dependent upon Ex11 + 32 T > C genotype. Compared to TT carriers who reported < 7 h/week of sun exposure, CC subjects with < 7 h/week of sun exposure had an increased risk of NHL (OR = 1.9, 95% CI 0.8–4.4, P_interaction = 0.16), while the relative risks for other CC carriers approached unity with increasing level of sun exposure. This pattern of effects was especially apparent for follicular lymphoma (for CC genotype and < 7 h/week of exposure: OR 6.3, 95% CI 1.9–22, P_interaction = 0.004), and was consistently observed across measures of reported sun exposure for different periods of life. As IVS10 + 283G > A is correlated with Ex11 + 32T > C in our population (r ² = 0.95), results were equivalent for those with the IVS10 + 283 AA genotype. No evidence of interaction with cytokine gene variants was observed. Conclusions Our results suggest that the inverse association between UV exposure and NHL risk may be mediated by the vitamin D pathway. Further investigation of this finding in other studies is warranted. The U.S. Government's right to retain a non-exclusive, royalty-free license in and to any copyright is acknowledged.     

Sunlight,hormone replacement status and colorectal cancer risk in postmenopausal women

A reanalysis of the Women's Health Initiative (WHI) randomized clinical trial found a significant interaction between supplementation with vitamin D/calcium and estrogen therapy and the risk of colorectal cancer risk, with reduced risks from supplementation limited to the placebo arms of the estrogen trials. To explore whether the vitamin D effects are modified by estrogen therapy, we report a largely cross‐sectional, analysis of the association between sun exposure, which is an important vitamin D source, and colorectal cancer risk among postmenopausal women in the U.S. Radiologic Technologists study. Among 21,695 participants, there were a total of 108 cases. Sun exposure was based on time outdoors and on ambient ultraviolet radiation (UV) exposure based on residence linked to erythemal exposures derived from the Total Ozone Mapping Spectrometer database. Although there was no relationship between outdoor time or ambient UV measure and colorectal cancer risk in current hormone replacement therapy (HRT) users, in never/past HRT users, there was an inverse association with higher ambient UV exposure, RR for highest vs. lowest tertile = 0.40; 95% CI 017, 0.93; p for trend = 0.04. Non‐significant lower risks were also associated with higher levels of outdoor time (≥3.5 hr/week) in never/past HRT users. The interaction between both indicators of sun exposure and HRT and CRC risk was not significant. These data, although exploratory, are consistent with evidence from the WHI suggesting a decrease in colorectal cancer risk may be associated with vitamin D exposure among postmenopausal women who are not taking HRT, but not among current HRT users.     

Anthropometrics,Physical Activity,Related Medical Conditions,and the Risk of Non-Hodgkin Lymphoma

Background: Recent reports suggest that obesity, or conditions associated with obesity, might be risk factors for non-Hodgkin lymphoma (NHL), a cancer with dramatically increasing incidence in western countries over the last several decades. Physical inactivity increases the risk of obesity and of type 2 diabetes, but there are few data on the association of physical activity with risk of NHL. Methods: We evaluated these factors in a population-based case–control study conducted in Detroit, Iowa, Los Angeles, and Seattle from 1998 to 2000. Incident HIV-negative NHL cases aged 20–74 years were rapidly reported in each area (n = 1321). Controls were identified through random digit dialing and Medicare files, and were frequency matched to cases on sex, age, race, and study site (n = 1057). Risk factor data were collected by in-person interviews and self-administered questionnaires. Unconditional logistic regression was used to estimate the odds ratio (OR) and 95% confidence intervals (CI), adjusted for age, sex, race and study center. Results: High body mass index (OR = 1.73 for 35+ versus <25 kg/m²; 95% CI 1.15–2.59) and history of gallstones (OR = 1.95, 95% CI 1.11–3.40) were positively associated with diffuse NHL, but were not associated with follicular or all NHL combined. Height was positively associated with risk of all NHL combined (OR = 1.38 for >70 versus <65 inches; 95% CI 0.98–1.94), and positive associations were apparent for both diffuse and follicular NHL. Non-occupational physical activity was inversely associated with risk of all NHL combined (ORs with increasing level: 1, 0.75, 0.71, 0.55, 0.68; p-trend = 0.04) and for diffuse and follicular NHL. We observed no association of total energy intake, type 2 diabetes, or hypertension with risk of NHL. In a multivariable model to predict risk of diffuse NHL, BMI (OR = 2.15 for 35+ versus <25 kg/m²; 95% CI 1.09–4.25) and height (OR = 1.63 for 71+ versus <65 inches; 95% CI 0.75–3.57) were positively associated with risk while physical activity was weakly and inversely associated risk (ORs with increasing level: 1, 0.76, 0.72, 0.78, 0.82; p-trend = 0.9). Conclusion: BMI and history of gallstones were positively associated with risk of diffuse NHL, supporting a role for obesity in this NHL subtype. Height was positively associated with NHL risk across subtypes, and suggests a role for early life nutrition in NHL risk. Non-occupational physical activity was only weakly and inversely associated with NHL risk after adjustment for obesity, height and alcohol use.     

Relation of body mass index to cancer risk in 362,552 Swedish men

Background Obesity has been linked with increased risk for cancers of the colon, kidney, breast, endometrium and gallbladder. For other cancer sites, the relationship with obesity is less well quantified, and the effect of weight change on cancer risk is unclear. Methods We examined the health records of 362,552 Swedish men who underwent at least one physical examination from 1971 to 1992, and were followed until death or the end of 1999. Incident cancer cases were identified by linkage to the Swedish cancer registry. Poisson regression models were used to estimate relative risks of cancer for both body-mass index (BMI) at baseline exam and, in a subgroup of 107,815 men, change in BMI after six years of follow-up, adjusting for age and smoking status. Results Compared to men of normal weight, obese men had a significantly increased risk of all cancers combined (RR = 1.1; 95% CI = 1.0–1.2). The risks were most pronounced for esophageal adenocarcinoma (RR = 2.7; 95% CI = 1.3–5.6), renal cell carcinoma (RR = 1.8; 95% CI = 1.4–2.4), malignant melanoma (RR = 1.4; 95% CI = 1.1–1.7), and cancers of the colon (RR = 1.7; 95% CI = 1.5–2.0), rectum (RR = 1.4; 95% CI = 1.1–1.7), and liver (RR = 3.6; 95% CI = 2.6–5.0). Risk of esophageal squamous cell carcinoma was elevated for underweight men whose BMI was less than 18.5 (RR = 3.1; 95% CI = 1.1–8.3). An excess risk for cancers of the pancreas and connective tissue was observed only among nonsmokers. Compared to men whose weight remained stable, men with more than a 15% increase in BMI after six years of follow-up had an elevated risk of pancreas and renal cell cancers. Conclusions Obesity and weight gain increase the risk for several forms of cancer in men, and underscore the need for further study into carcinogenic mechanisms and preventive interventions.     

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.     

A Pooled Analysis of 12 Cohort Studies of Dietary Fat, Cholesterol and Egg Intake and Ovarian Cancer

Fat and cholesterol are theorized to promote ovarian carcinogenesis by increasing circulating estrogen levels. Although case–control studies have reported positive associations between total and saturated fat intake and ovarian cancer risk, two cohort studies have observed null associations. Dietary cholesterol and eggs have been positively associated with ovarian cancer risk. A pooled analysis was conducted on 12 cohort studies. Among 523,217 women, 2,132 incident epithelial ovarian cancer cases were identified. Study-specific relative risks (RR) and 95% confidence intervals (CI) were calculated by Cox proportional hazards models, and then pooled using a random effects model. Total fat intake was not associated with ovarian cancer risk (pooled multivariate RR = 1.08, 95% CI 0.86–1.34 comparing ≥45 to 30–<35% of calories). No association was observed for monounsaturated, polyunsaturated, trans-unsaturated, animal and vegetable fat, cholesterol and egg intakes with ovarian cancer risk. A weakly positive, but non-linear association, was observed for saturated fat intake (pooled multivariate RR = 1.29, 95% CI: 1.01–1.66 comparing highest versus lowest decile). Results for histologic subtypes were similar. Overall, fat, cholesterol and egg intakes were not associated with ovarian cancer risk. The positive association for saturated fat intake at very high intakes merits further investigation.     

UV radiation exposure, skin type and lymphoid malignancies: results of a French case–control study

Objectives Investigating the relationship between skin type, UV exposure, and lymphoid malignancies (LM). Methods We conducted a hospital-based case–control study in France, including 813 incident cases of non-Hodgkin’s lymphoma (NHL), Hodgkin’s lymphoma (HL), lymphoproliferative syndrome (LPS) or multiple myeloma and 748 controls. Results Positive associations between HL and blond/red hair (OR = 1.8 [0.8–3.8]), very fair/fair skin (OR = 1.6 [1.0–2.5]) were observed. High propensity to burn was associated with HL (OR = 1.5 [1.0–2.2]) and LPS (OR = 1.4 [1.0–2.1]). Poor ability to tan was significantly associated with HL (OR = 1.7 [1.0–2.8]). Having light hair with high propensity to burn was associated with NHL (OR = 1.5 [0.9–2.5]) and significantly with HL (OR = 3.4 [1.4–8.4]). Having dark hair with high propensity to burn was significantly associated with LPS (OR = 1.5 [1.0–2.2]). The associations with HL and NHL were significant for men only, with significant interactions. Outdoors activities since leaving school or in the last decade were not related to LM. Only an almost negative trend was observed. Prior exposure to artificial UV was not associated with LM. Conclusion These results suggest a positive association between the most reactive and palest skin types and NHL or HL in men and do not rule out a slight negative relationship between UV exposure and LM.     

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.     

The effect of atopy,childhood crowding,and other immune-related factors on non-Hodgkin lymphoma risk

Objective Since adult immune responsiveness is influenced by early childhood exposures, we examined the role of family size, history of atopic disease, and other childhood immune-related exposures in a multi-center case–control study of NHL. Methods Interviews were completed with 1,321 cases ascertained from population-based cancer registries in Seattle, Detroit, Los Angeles and Iowa, and with 1,057 frequency-matched controls, selected by random-digit dialing and from the Medicare files database. Multivariable logistic regression was used to estimate risk. Results A history of any allergy (excluding drug allergies), decreased risk of all NHL (Odds Ratio [OR] = 0.7, 95% Confidence Interval [CI] = 0.6–1.0), diffuse large B-cell lymphoma [DLBCL] (OR = 0.6, 95% CI = 0.4–0.9), and follicular NHL (OR = 0.7, 95 CI = 0.5, 1.0). A similar effect was observed for hay fever. A history of eczema was associated with an increased risk of follicular lymphoma (OR = 1.9, 95% CI = 1.1–3.4), but not DLBCL (OR = 1.1, 95% CI = 0.6–2.0). Asthma did not affect risk. Youngest compared to oldest siblings had a 90% increased risk of DLBCL (95% CI = 1.2–3.1; p for trend with increasing birth order = 0.006), but not follicular lymphoma (OR = 1.1, 95% CI = 0.6–1.8). Conclusions We infer that some childhood and immune-related factors may alter NHL risk.     

Antioxidant intake from fruits,vegetables and other sources and risk of non‐Hodgkin's lymphoma: the Iowa Women's Health Study

Antioxidant nutrients found in fruits, vegetables and other foods are thought to inhibit carcinogenesis and to influence immune status. We evaluated the association of these factors with risk of non‐Hodgkin's lymphoma (NHL) overall and for diffuse large B‐cell lymphoma (DLBCL) and follicular lymphoma specifically in a prospective cohort of 35,159 Iowa women aged 55–69 years when enrolled at baseline in 1986. Diet was ascertained using a validated semiquantitative food frequency questionnaire. Through 2005, 415 cases of NHL (including 184 DLBCL and 90 follicular) were identified. Relative risks (RRs) and 95% confidence intervals (CIs) were estimated using Cox regression, adjusting for age and total energy. The strongest associations of antioxidants with risk of NHL (RR for highest versus lowest quartile; p for trend) were observed for dietary vitamin C (RR = 0.78; p = 0.044), α‐carotene (RR = 0.71; p = 0.015), proanthocyanidins (RR = 0.70; p = 0.0024) and dietary manganese (RR = 0.62; p = 0.010). There were no associations with multivitamin use or supplemental intake of vitamins C, E, selenium, zinc, copper or manganese. From a food perspective, greater intake of total fruits and vegetables (RR = 0.69; p = 0.011), yellow/orange (RR = 0.72; p = 0.015) and cruciferous (RR = 0.82; p = 0.017) vegetables, broccoli (RR = 0.72; p = 0.018) and apple juice/cider (RR = 0.65; p = 0.026) were associated with lower NHL risk; there were no strong associations for other antioxidant‐rich foods, including whole grains, chocolate, tea or nuts. Overall, these associations were mainly observed for follicular lymphoma and were weaker or not apparent for DLBCL. In conclusion, these results support a role for vegetables, and perhaps fruits and associated antioxidants from food sources, as protective factors against the development of NHL and follicular lymphoma in particular.     

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.     

Occupational exposure to pesticides and risk of hematopoietic cancers: meta-analysis of case–control studies

Objective In this study we conducted a meta-analysis of 13 case–control studies that examined the occurrence of hematopoietic cancers in pesticide related occupations in order to undertake a qualitative and quantitative evaluation of a possible relationship. Methods Pubmed databases were searched for case–control studies published between 1990 and 2005 investigating the relation between hematopoietic cancers and occupational exposure to pesticides. Fixed and random effect meta-analysis models were used depending on the presence of heterogeneity between studies. Results The overall meta-odds ratio obtained after pooling 44 ORs from 13 studies was 1.3 (95% CI: 1.3–1.5). We realized stratified analysis on three different types of hematopoietic cancers (non-Hodgkin lymphoma (NHL), leukemia and multiple myeloma). A significant increased risk of NHL was found (OR = 1.35; 95% CI = 1.2–1.5). Moreover, increased risks of Leukemia (OR = 1.35; 95% CI = 0.9–2) and multiple myeloma (OR = 1.16; 95% CI = 0.99–1.36) were also detected but these results were not statistically significant. Significant heterogeneity existed among the different studies and a publication bias was detected. Therefore, a meta-regression was carried out. Our results showed that a long period of exposure (more than 10 years) provided an increase in the risk of all hematopoietic cancers and for NHL by fractions of 2.18 (95% CI = 1.43–3.35) and 1.65 (95% CI = 1.08–2.51), respectively. Conclusions: The overall meta-odds ratio suggests that there is a significantly positive association between occupational exposure to pesticides and all hematopoietic cancers as well as NHL. A major limitation of our meta-analysis is the lack of sufficient data about exposure information and other risk factors for hematopoietic cancer (genetic predisposition, ethnic origin, immunodepression…). In addition, data concerning specific subtypes of hematopoietic cancers are often confusing. Thus, future epidemiological studies should undertake a major effort to assess the identity and the level of pesticides exposure and should control for the most likely potential confounders.     

Family history is a significant risk factor for pancreatic cancer: results from a systematic review and meta-analysis

Epidemiologic evidence suggests a family history of pancreatic cancer (PC) is a risk factor for the disease, yet the magnitude of risk varies between studies. We performed a systematic review of studies that quantified familial risks of PC, and through a meta-analysis, obtained more precise estimates of familial risk. A MEDLINE search identified published studies that reported relative risks (RR) of PC associated with a family history of the disease. A random effects model was used to summarize study-specific RRs and 95% confidence intervals (CI). Sensitivity and sub-group analyzes were performed. Seven case–control and two cohort studies involving 6,568 PC cases were identified. There was no evidence of statistical heterogeneity between studies (I² = 0%; P = 0.483). Results from case–control (RR = 2.82; 95% CI: 1.99–3.66) and cohort (RR = 1.62; 95% CI: 1.28–1.97) studies showed a significant increase in PC risk associated with having an affected relative, with an overall summary RR = 1.80 (95% CI: 1.48–2.12). Similar RR were observed for early (RR = 2.69; 95% CI: 0.56–4.82) and later (RR = 3.41; 95% CI: 0.79–6.03) onset disease in the index case. Data was too sparse to generate an overall summary RR based on the number or type of affected relatives. Individuals with a family history of PC have nearly a two-fold increased risk for developing PC compared to those without such a history. Families with two or more PC cases may benefit from comprehensive risk assessment that involves collection of detailed family history information and data regarding various risk factors for PC, especially smoking history. Those at highest risk may be referred to screening programs and studies; these are important steps toward early detection and greater odds of surviving this disease.     

Personal and Occupational Exposure to Organic Solvents and Risk of Non-Hodgkin’s Lymphoma (NHL) in Women (United States)

Objectives: The authors assessed whether home and occupational exposure to organic solvents is associated with risk of NHL in women. Methods: A population-based, incidence case-control study was conducted in upstate New York, involving 376 NHL cases and 463 population controls selected from the Medicare beneficiary files and State driver’s license records. Exposure information was obtained by telephone interview. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using an unconditional logistic regression model, adjusting for a number of risk factors for NHL. Results: Overall, history of exposure to organic solvents was not associated with the risk of NHL. A statistically significant increase in risk associated with occupational exposure was observed only for the subjects whose first exposure occurred before 1970 (OR=1.87, 95% CI 1.03–3.40). When occupational and home exposures to paint thinners/turpentine were combined and analyzed together, the risk of NHL associated with any exposure, compared to no exposure at either job or home, was a statistically significantly increased (OR=1.46, 95% CI: 1.05–2.03). This observation was more pronounced for B-cell lymphoma and for low-grade lymphoma with ORs of 1.52 (95 CI: 1.08–2.14) and 2.20 (95% CI; 1.42–3.41), respectively. Conclusions: The results of this case-control study do support of a major role of organic solvents in the development of NHL among women currently living in the US. However, relatively intensive exposure in past occupations and use of paint thinners/turpentine may deserve further investigation.     

Aspirin and cancer risk: an updated quantitative review to 2005

Aspirin has been associated to a reduced risk of colorectal, and possibly of a few other common cancers. Epidemiological studies on aspirin and cancer risk published up to December 2005 have been reviewed, and pooled relative risks (RR) for several cancers have been provided. Besides a reduction in the risk of cancer of the colorectum (RR = 0.71, 95% confidence interval, CI: 0.67–0.75), there is evidence—although more limited, and mainly from case–control studies—that aspirin has a favourable effect on cancers of the esophagus (RR = 0.72, 95% CI: 0.62–0.84), stomach (RR = 0.84, 95% CI: 0.76–0.93), breast (RR = 0.91, 95% CI: 0.88–0.95), ovary (RR = 0.89, 95% CI: 0.78–1.02) and lung (RR = 0.94, 95% CI: 0.89–1.00). The role of aspirin on other cancers, such as pancreatic, prostate, bladder cancer, and non-Hodgkins’ lymphomas is less clear, and an increase of risk has been suggested for kidney cancer. For most cancer sites, however, significant heterogeneity between studies, and particularly across study design, was found, with a reduction in risk generally stronger in case–control than in cohort studies. Further, notwithstanding the large amount of epidemiological evidence, substantial uncertainties remain about the proper aspirin dose and duration of treatment. This work was conducted with the contribution of the Italian Association for Cancer Research, the Italian League Against Cancer, and the Italian Ministry of Education (PRIN 2005).     

Risk of non-Hodgkin lymphoma and nitrate and nitrite from the diet in Connecticut women

It has been estimated that 65,980 individuals were diagnosed with non-Hodgkin lymphoma (NHL) and 19,500 died from NHL in the United States in 2009. Although established risk factors such as immunodeficiency and viral infections may be responsible for a portion of the cases, the majority of NHL cases remain unexplained. Dietary nitrate and nitrite intake are exposures of particular interest for NHL risk as they are precursors in the endogenous formation of N-nitroso compounds, which cause lymphomas in animal studies. We investigated NHL risk overall and by histologic type in relation to dietary nitrate and nitrite intake in a population-based case–control study of 1,304 women in Connecticut. Nitrate and nitrite intake were assessed using a 120-item food frequency questionnaire. We found no association between risk of NHL overall and dietary nitrate and a slightly increased risk of NHL with higher dietary nitrite intake (highest vs. lowest intake quartile OR = 1.4; 95% CI: 0.9–2.2). When we evaluated intake by subtype, a significant positive trend was observed for follicular lymphoma and nitrate (p-trend = 0.04) and nitrite (p-trend < 0.01) with an over twofold risk in the highest nitrite intake quartile (OR = 2.3; 95% CI: 1.1–4.9). An increased risk in the highest quartile of nitrite intake was also observed for T-cell lymphoma (OR = 3.4; 95% CI: 1.0–11.9). Animal products containing nitrite were more strongly associated with risk of follicular lymphoma; whereas, both animal and plant sources of nitrite were associated with elevated ORs for T-cell lymphoma. Our results confirm a previous finding for nitrite intake and NHL risk and highlight the importance of evaluating histologic type. We conclude that these results should be replicated in a larger study with data on drinking water as well as dietary sources of nitrate intake.