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Retroperitoneal sarcoma: a population-based analysis of epidemiology, surgery, and radiotherapy.

BACKGROUND: No population-based studies of retroperitoneal sarcoma (RPS) have been conducted, and the use and timing of adjuvant radiotherapy for RPS is controversial. The objective of this study was to examine the incidence and treatment of RPS, specifically regarding the use of adjuvant radiotherapy. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was used to evaluate the incidence of RPS over a 29-year period (1973-2001). The rate of surgery, the rate and timing of adjuvant radiotherapy, and the influence of demographic factors on treatment were evaluated. RESULTS: A total of 2348 cases of RPS were identified. The mean annual incidence of RPS was 2.7 cases per 10(6) persons and did not change significantly over time (2.6 in 1973 vs. 2.8 in 2001; P = .92). Most patients (1654; 70.4%) underwent surgical resection. Radiotherapy was used in 428 patients (25.9%) who underwent surgery; radiation was given postoperatively in 366 (85.5%), preoperatively in 20 (4.7%), and intraoperatively or unknown in 42 (9.8%). Patients who received any adjuvant radiotherapy were on average 5 years younger than those who underwent surgery alone (P < .0001). Radiotherapy was more commonly used among whites than African Americans (25.8% vs. 16.7%; P = .02) and there was significant variation in the use of adjuvant radiotherapy by geographic location (P = .003). On multivariate analysis, race (P = 0.004), age (P < .0001), and geographic location (P = .006) were independently associated with the use of adjuvant radiotherapy. CONCLUSION: The incidence of RPS, a rare disease, appears stable. Most patients who undergo surgery do not receive any adjuvant radiotherapy, and very few receive preoperative radiotherapy. Differences in adjuvant radiotherapy use related to demographic and geographic factors suggest that at least some treatment variations reflect differences in individual and institutional practice patterns.

Adolescent↗

Generalizability of cancer clinical trial results: prognostic differences between participants and nonparticipants.

BACKGROUND: The generalizability of clinical trial results is questionable, because fewer than 5% of cancer patients participate. The authors examined the comparability of clinical trial participants and nonparticipants and the potential impact of differences. METHODS: A retrospective cohort of 19,340 cancer patients who were diagnosed between January 1990 and December 1997 was characterized by trial participation. The distributions of prognostically important factors among trial participants were compared with the distributions among nonparticipants and the population of patients diagnosed during the same period in the Surveillance, Epidemiology, and End Results population. The impact of these factors on survival was examined by using a Cox proportional hazards analysis. RESULTS: Trial participants were younger and had better performance status and fewer comorbid conditions compared with nonparticipants. However, participants were more likely to have locally advanced disease, positive lymph node status, poorly differentiated tumors, liver metastases, and multiple metastatic sites. The former factors were associated with significantly longer survival, whereas the later factors were associated with significantly shorter survival. CONCLUSIONS: The lack of comparability between trial participants and nonparticipants called into question the generalizability of clinical trial results. Although selective recruitment for clinical trials is justified, the authors encourage the use of population-based trials of effectiveness in "all comers."

Adult↗

Radical prostatectomy for clinical T4 prostate cancer.

BACKGROUND: Occasionally, patients with clinical T4 (cT4) prostate cancer undergo surgery. Published data on outcomes after radical prostatectomy (RP) in patients with such advanced stage disease and on the impact of adjuvant radiation therapy (RT) and hormone therapy (HT) are nonexistent. METHODS: Data from the Surveillance Epidemiology and End Results (SEER) data base were reviewed for the 7-year period from 1995 to 2001. Specifically, data were analyzed for 1093 patients with cT4, lymph node-negative or lymph node-positive, M0 prostate cancer without distant lymph node involvement or a history of other cancer. Using follow-up data through 2002, postdiagnosis survival was examined in 5 treatment groups: radical prostatectomy (RP) either alone or in combination with other therapy, radiation therapy (RT) alone, hormone therapy (HT) alone, RT plus HT, and no treatment (NT). All results were expressed as 1-year, 3-year, and 5-year observed survival and corresponding relative survival. Mortality across treatment categories was compared by using a Cox proportionate hazards model controlling for age, year of diagnosis, race, tumor grade, regional lymph node involvement, clinical tumor extension, and SEER registry. RESULTS: Observed and relative survival rates were lowest among patients who received NT and highest among patients who underwent RP. Adding adjuvant RT or HT to RP conferred no survival benefit. Multivariate survival analyses revealed a significant increase in mortality among HT-only patients and among patients who received NT compared with patients who underwent RP. The differences in survival among treatment types were most pronounced in a relatively small group of patients who had positive regional lymph node extension. In all other patients, the results suggested a modest (but not significant) improvement in survival after RT plus HT. CONCLUSIONS: SEER data revealed that patients who underwent RP for cT4 prostate cancer had increased survival compared with patients who received RT alone or HT alone and had a survival comparable to that of patients who received RT plus HT. The benefit of RP appears to be limited to a relatively small subset of patients who have regional lymph node extension.

Aged↗

Hodgkin disease survival in Europe and the U.S.: prognostic significance of morphologic groups.

BACKGROUND: The survival of patients with Hodgkin disease (HD) varies markedly across Europe and generally is shorter than the survival of patients in the U.S. To investigate these differences, the authors compared population-based HD survival in relation to morphologic type among populations in Europe and the U.S. METHODS: The authors analyzed 6726 patients from 37 cancer registries that participated in EUROCARE-3 and 3442 patients from 9 U.S. Surveillance, Epidemiology, and End Results (SEER) registries. Patients were diagnosed during 1990 to 1994 and were followed for at least 5 years. The European registries were grouped into EUROCARE West, EUROCARE UK, and EUROCARE East. Morphologic groups were nodular sclerosis, mixed cellularity, lymphocyte depletion, lymphocyte predominance, and not otherwise specified (NOS). The influence of morphology on geographic differences in 5-year relative survival was explored by using multiple regression analysis. RESULTS: In the model that was adjusted by age, gender, and years since diagnosis, the relative excess risk (RER) of death was 0.93 (95% confidence interval [95% CI], 0.81-1.05) in EUROCARE West, 1.15 (95% CI, 1.04-1.28) in EUROCARE UK, and 1.39 (95% CI, 1.21-1.60) in EUROCARE East (compared with the SEER data). When morphology was included, EUROCARE UK and SEER no longer differed (RER, 1.06; 95% CI, 0.95-1.18). Morphology distribution varied markedly across Europe and much less in the U.S., with nodular sclerosis less common in Europe (45.9%) than the U.S. (61.7%). The RER data showed that patients who had lymphocyte depletion, NOS, and mixed cellularity had a significantly worse prognoses compared with patients who had nodular sclerosis, whereas patients who had lymphocyte predominance had the best prognosis. CONCLUSIONS: The current results provide population-based evidence that morphology strongly influences the prognosis of patients with HD. However differences in the morphologic case mix explains only some of the geographic variations observed in survival.

Adolescent↗

Adolescents and young adults with cancer: the scope of the problem and criticality of clinical trials.

In the U.S., older adolescents and young adults with cancer have benefited less from therapeutic advances than did either younger or older patients. One factor that may explain this deficit is the relative lack of participation of patients in this age group on clinical trials of therapies that could improve their outcome. Comparisons were made of the participation of cancer patients on clinical trials in the U.S., as a function of patient age, with the change in national cancer mortality rate; and Surveillance, Epidemiology, End Results (SEER) cancer survival rate as a function of age. The participation rate in cancer treatment trials has been strikingly lower in 15-34-year-olds than in younger or older patients. The nadir has been apparent for both males and females in all of the major ethnic and racial groups. The national cancer mortality reduction and SEER survival improvement shows a similar age dependence. In the U.S., the age-dependence of cancer treatment trial participation, and of improvement in survival prolongation and cancer death rates, are correlated. Regardless of whether there is a causal relationship, the impact on the older adolescent and young adult U.S. population is substantial, adversely affecting the national cost of healthcare, the person-years of life lost, the loss of young people entering the job market, and the scientific knowledge and social implications of cancer during adolescence and early adulthood. National initiatives are underway to address these issues, with special emphasis on increasing the availability and access to clinical trials designed for older adolescents and young adults.

Adolescent↗

Significant regional variation in adequacy of lymph node assessment and survival in gastric cancer.

BACKGROUND: Lymph node (LN) status is a major determinant of prognosis and treatment of gastric adenocarcinoma. The 1997 American Joint Commission on Cancer/Union Internationale Contre le Cancer guidelines were revised, requiring examination of > or =15 LN for staging. METHODS: We investigated compliance with these guidelines and the correlation with overall survival (OS) by analyzing 10,807 resected gastric cancers in the Surveillance, Epidemiology and End Results (SEER) database, 1988-2002. Kaplan-Meier survival curves were constructed; survival was compared by using Cox proportional hazards. RESULTS: Overall, 29% of cases had > or =15 LN examined. After 1997, the median number of LN assessed increased from 9 to 10 (P < .0001). Factors predictive of adequate LN assessment (ALNA) were higher stage, worse grade, age <74 years, later year of diagnosis, nonwhite race, more extensive surgery, female sex, and SEER region. Differences in the rate of ALNA between regions were noted, ranging from 19.7-53% (P < .0001). Of T1N0 patients, 19% had ALNA. Improved OS was predicted by earlier stage, lower grade, marital status, Asian race, younger age, T-stage, female sex, SEER region, and ALNA. Median OS was highest in the region with the best ALNA rate and worst in the region with the lowest (33 mos vs. 17 mos, P < .0001). Inadequate LN assessment led to poorer survival at every stage (P < .001). CONCLUSION: The overwhelming majority of patients have an inadequate LN assessment. ALNA was associated with improved OS, with significant variation across regions. Understaging due to inadequate LN assessment may affect eligibility for adjuvant therapy. Education is required to improve LN retrieval.

Adolescent↗

Prognosis of medullary thyroid carcinoma: demographic, clinical, and pathologic predictors of survival in 1252 cases.

BACKGROUND: Medullary thyroid cancer (MTC) is a rare cancer. There is a relative paucity of data over the last decade with regard to the prognosis of these patients. Therefore, the authors used the population-based Surveillance, Epidemiology, and End Results (SEER) registry to update what to their knowledge is one of the largest series of patients with MTC reported to date. METHODS: All patients with a diagnosis of MTC with active follow-up in the SEER database from 1973 to 2002 were included. Univariate and multivariate regression analyses were used to assess the associations between demographic, clinical, and pathologic characteristics of patients and survival. RESULTS: A total of 1252 patients with MTC were identified over 29 years of follow-up. In all, 87% of patients were white and 60% were female, with a mean age of 50 years. Although many variables were significant on univariate analysis, SEER stage and age at diagnosis were found to be the strongest predictors of survival in the multivariate analysis. Prognosis was poor in patients with advanced disease (hazards ratio [HR], 4.47), or those age >65 years (HR, 6.55). Patients who underwent surgery fared better than those who did not. Overall, 51% of patients had less than the currently recommended treatment guidelines for MTC. Adjuvant radiation therapy was found to be independently associated with a decreased survival (HR, 1.65). CONCLUSIONS: Stage of disease and age at diagnosis were found to be the strongest predictors of survival for patients with MTC. To the authors' knowledge there has been no change in stage at diagnosis or a significant improvement in survival noted over the last 30 years. Many patients underwent surgery that was deemed less than optimal for stage of disease.

Age of Onset↗

Timing of adjuvant chemotherapy initiation after surgery for stage III colon cancer.

BACKGROUND: An important advance in medical oncology has been the use of adjuvant chemotherapy for lymph node-positive colon cancer. However, to the authors' knowledge, the effect of the interval between surgery and the initiation of chemotherapy on survival has not been investigated. METHODS: The authors analyzed predictors and outcomes of time intervals to treatment after surgery among patients older than 65 years who were diagnosed with stage III colon cancer between 1992 and 1999 using Surveillance, Epidemiology, and End Results (SEER)-Medicare data. Linear and logistic regression analyses were used to model predictors of delay, and Cox proportional hazards models were used to analyze the impact of treatment timing on survival. RESULTS: Among 4382 patients with colon cancer, 1122 patients (26%) began adjuvant chemotherapy within 1 month, 2391 patients (55%) began adjuvant chemotherapy in 1 to 2 months, 454 patients (10%) began adjuvant chemotherapy in 2 to 3 months, and 415 patients (9%) began adjuvant chemotherapy >/=3 months after surgery. Intervals of >/=3 months (delay) were associated with older age, increased comorbid conditions, well/moderately differentiated grade, and being unmarried. Colon cancer-specific mortality was associated with a delay in the initiation of chemotherapy (hazards ratio [HR], 1.48; 95% confidence interval [95% CI], 1.15-1.92), advanced age, increased comorbidity, poorly differentiated tumor grade, the presence of >/=4 positive lymph nodes, and undergoing surgery in a nonteaching hospital. All-cause mortality was associated with intervals >2 months between surgery and chemotherapy (2 to 3 months: HR, 1.41; 95% CI, 1.15-1.74; >/=3 months: HR, 1.62; 95% CI, 1.31-1.99) compared with <1 month. CONCLUSIONS: In the older population that was studied, only 9% of patients initiated adjuvant chemotherapy >3 months after the date of curative surgery. However, delay in initiation was associated with both cancer-specific and all-cause mortality. Determining whether these results were because of chemotherapy timing or other associated factors will require further study.

Age Factors↗

Determination of threshold values for determining the size of the fraction of steroid hormone receptor-positive tumor cells in paraffin-embedded breast carcinomas.

BACKGROUND: For 4 years we used a multiparameter DNA flow cytometric (MP-FCM) technique to assess steroid hormone receptor expression in the diagnostic workup of routinely processed formalin-fixed, paraffin-embedded breast carcinomas as an alternative to immunohistochemistry (IHC) for the quantification of hormone receptor-positive cells. In all cases a positive fraction of hormone receptor-expressing epithelial cells was detected. This observation raised the question of what the cutoff value might be to distinguish receptor-negative from receptor-positive tumors. METHODS: In our search for a possible threshold value of positivity for estrogen receptor (ER) and progesterone receptor (PR) in MP-FCM, we developed four steps. First, we compared IHC results in our own laboratory with the results obtained by MP-FCM on a small series of breast tumors (n = 42). Second, after collecting our first 843 tumors, we made a comparison with the literature of the distribution of receptor positivity according to age classes. Third, using the most likely threshold that resulted from this comparison, we compared a subset of 340 node-negative tumors for their combined ER/PR profiles with the data from a similar group of node-negative tumor cases from the National Cancer Institute's Surveillance, Epidemiology and End-Result (SEER) study. Fourth, with the results of these comparisons, we prospectively collected IHC data and MP-FCM results of the same tumor samples for a period of 1 year. In this way, we collected data for an additional 180 tumors. RESULTS: The first step in this process resulted in an previous publication where 20% of steroid hormone receptor-positive cells seemed to be an acceptable cutoff point for positivity. However, the second step provided the best correlation at approximately 35% of ER reactive cells in the cytokeratin-positive cell population. With this cutoff, the distribution of combined ER/PR profiles in our patient population of node-negative breast cancers also showed a distribution similar to the data from the SEER study. The fourth step, using the 35% threshold value, resulted in a good correlation (r = 0.85, P < 0.0001) for ER and PR between IHC and MP-FCM in the 180 tumors investigated. CONCLUSION: By comparing in-house data with those from large external data collections in the literature, a threshold percentage can be defined that distinguishes steroid hormone receptor-negative from hormone receptor-positive tumors. As a result, information about DNA content and cell cycle distribution can be obtained. This observational study provides additional support to our opinion that MP-FCM is an alternative for IHC determination of ER and PR positivity. It is more objective and quantification can be done more appropriately. The additional value of this approach is that we generate continuous variables of ER/PR content instead of categorical classes, which can be used at different threshold levels for evaluation of clinical relevance.

Adult↗

Evaluating bias due to population stratification in case-control association studies of admixed populations.

The potential for bias from population stratification (PS) has raised concerns about case-control studies involving admixed ethnicities. We evaluated the potential bias due to PS in relating a binary outcome with a candidate gene under simulated settings where study populations consist of multiple ethnicities. Disease risks were assigned within the range of prostate cancer rates of African Americans reported in SEER registries assuming k=2, 5, or 10 admixed ethnicities. Genotype frequencies were considered in the range of 5-95%. Under a model assuming no genotype effect on disease (odds ratio (OR)=1), the range of observed OR estimates ignoring ethnicity was 0.64-1.55 for k=2, 0.72-1.33 for k=5, and 0.81-1.22 for k=10. When genotype effect on disease was modeled to be OR=2, the ranges of observed OR estimates were 1.28-3.09, 1.43-2.65, and 1.62-2.42 for k=2, 5, and 10 ethnicities, respectively. Our results indicate that the magnitude of bias is small unless extreme differences exist in genotype frequency. Bias due to PS decreases as the number of admixed ethnicities increases. The biases are bounded by the minimum and maximum of all pairwise baseline disease odds ratios across ethnicities. Therefore, bias due to PS alone may be small when baseline risk differences are small within major categories of admixed ethnicity, such as African Americans.

Black or African American↗

The impact of including future medical care costs when estimating the costs attributable to a disease: a colorectal cancer case study.

A source of controversy in the economic literature concerns whether to include or exclude future medical care costs when computing attributable costs for lifesaving interventions. Although it is hypothesized that including future medical care costs will offset the cost savings achieved through prevention, the magnitude of the effect is not known. The objectives of the present study are to develop a methodology for estimating the excess costs of care among colorectal cancer patients, including and excluding future costs of care, and comparing these results with previous studies that do not include costs in added years of life. Subjects in the study included those identified with colorectal cancer drawn from the Surveillance, Epidemiology and End Results (SEER)-Medicare database and an age- and gender-matched control group drawn from the general Medicare population. Using the Kaplan-Meier Sample Average estimator, we directly estimate expected 11-year costs, and then, with the addition of some simple extrapolating assumptions, determine expected 25-year costs. The latter time horizon captures lifetime costs for over 90% of the cohort. Males results for discounted, stage-specific 11- versus 25-year excess costs: in situ, 22411 dollars versus 23494 dollars; Stage 1, 29365 dollars versus 32510 dollars; Stage 2, 28114 dollars versus 25263 dollars; Stage 3, 27397 dollars versus 19647 dollars; Stage 4, 3006 dollars versus 7837 dollars. Trends were similar for females. It can be concluded that adding costs of care in future years for those whose colorectal cancer is prevented owing to screening greatly alters the estimate of lifetime excess costs for colorectal cancer patients, and can produce negative results for advanced stage disease. The results emphasize the need to adopt a standard approach for dealing with future costs when evaluating lifesaving interventions for cost-effectiveness analyses.

Cohort Studies↗

A propensity score approach to estimating the cost-effectiveness of medical therapies from observational data.

Health summary measures are commonly used by policy makers to help make decisions on the allocation of societal resources for competing medical treatments. The net monetary benefit is a health summary measure that overcomes the statistical limitations of a popular measure namely, the cost-effectiveness ratio. We introduce a linear model framework to estimate propensity score adjusted net monetary benefit. This method provides less biased estimates in the presence of significant differences in baseline measures and demographic characteristics between treatment groups in quasi-randomized or observational studies. Simulation studies were conducted to better understand the utility of propensity score adjusted estimates of net monetary benefits when important covariates are unobserved. The results indicated that the propensity score adjusted net monetary benefit provides a robust measure of cost-effectiveness in the presence of hidden bias. The methods are illustrated using data from SEER-Medicare for the treatment of bladder cancer.

Aged↗

Lung cancer rates convergence in young men and women in the United States: analysis by birth cohort and histologic type.

Age-specific rates of lung cancer have been consistently higher for men than for women in the United States, due primarily to different patterns of cigarette smoking. Gender differences in cigarette smoking have diminished in recent birth cohorts, however, especially among whites. We used U.S. population-based incidence and mortality data and examined trends in age-specific rates of lung cancer by birth cohort according to gender, ethnic group, and histology to evaluate the generational changes in U.S. lung cancer risk for men vs. women. All tests of statistical significance are 2-sided (95% confidence interval [CI]). Lung cancer mortality rates have converged between men and women born after 1960, especially in whites. The male-to-female (M:F) mortality rate ratio for ages 35-39 years decreased from 3.0 (95% CI = 2.7-3.4) around the 1915 birth cohort to 1.1 (95% CI = 1.0-1.1) around the 1960 birth cohort among whites and from 4.0 (95% CI = 3.2-5.0) around the 1925 birth cohort to 1.5 (95% CI = 1.3-1.7) around the 1960 birth cohort among blacks. Similarly, incidence rates for white men and women converged rapidly for adenocarcinoma, small cell carcinoma, and large cell carcinoma, but less so for squamous cell carcinoma. These findings reflect the smoking patterns among white and black men and women: cigarette smoking prevalence at age 24 was essentially equal among white men and women born after 1960 but continued to be higher in black men than women. The convergence of lung cancer death rates among men and women born after 1960s supports the idea that males and females maybe equally susceptible to develop lung cancer from a given amount of cigarette smoking, rather than the hypothesis that women are more susceptible.

Adenocarcinoma↗

Important increase of invasive lobular breast cancer incidence in Geneva, Switzerland.

A recent paper from the United States reported a sharp and unexplained increase in invasive lobular breast cancer incidence since 1977 (Li et al., Cancer 2000;88:2561-9). We investigated if this trend was also present in Geneva, Switzerland, where breast cancer incidence is one of the highest in Europe. We analyzed trends in breast cancer incidence according to histologic subtype, age and stage, to clarify the pattern. Our population-based study includes all histologically confirmed invasive breast carcinomas (n = 6,247) recorded between 1976 and 1999 at the Geneva Cancer Registry. Breast histology was classified as ductal carcinoma, lobular carcinoma and other. Incidence trends were studied by log-linear regression analyses. Models including effects of age, period and birth cohorts were used to describe rising incidence trends. The incidence of ductal carcinoma increased 1.2% per year (p(trend) < 0.001) from 85.2 to 110.1/100,000. This increase concerned women aged 50-69 years and early-stage tumors. Lobular cancer incidence increased disproportionately (14.4% per year, p(trend) < 0.01) and rose from 2.9 to 20.5/100,000. This increase affected all age categories and both localized and advanced stages. In addition, a strong age-cohort effect was present (p < 0.05), and women aged 50-59 years born after 1944 experienced the most marked increase. Our study shows a disproportionate increase of lobular breast cancer incidence compared to ductal cancer incidence. Contrary to ductal cancer, trends for lobular cancer are unlikely to be explained by increased use of screening mammography. Other explanations must be researched, in particular the role played by hormone replacement therapy.

Aged↗

Green tea and risk of breast cancer in Asian Americans.

There is substantial in vitro and in vivo evidence implicating tea polyphenols as chemopreventive agents against various cancers. However, epidemiologic data obtained from mainly Western populations are not supportive of a protective role of tea, mainly black tea, in the etiology of breast cancer. Much less is known about the relationship between green tea and breast cancer risk. During 1995-1998, we conducted a population-based, case-control study of breast cancer among Chinese, Japanese and Filipino women in Los Angeles County and successfully interviewed 501 breast cancer patients and 594 control subjects. Detailed information on menstrual and reproductive factors; dietary habits, including intake of black and green tea; and other lifestyle factors was collected. Risk of breast cancer was not related to black tea consumption. In contrast, green tea drinkers showed a significantly reduced risk of breast cancer, and this was maintained after adjusting for age, specific Asian ethnicity, birthplace, age at menarche, parity, menopausal status, use of menopausal hormones, body size and intake of total calories and black tea. Compared to women who did not drink green tea regularly (i.e., less than once a month), there was a significant trend of decreasing risk with increasing amount of green tea intake, adjusted odds ratios being 1.00, 0.71 (95% confidence interval [CI] 0.51-0.99) and 0.53 (95% CI 0.35-0.78), respectively, in association with no, 0-85.7 and >85.7 ml of green tea per day. The significant inverse association between risk of breast cancer and green tea intake remained after further adjustment for other potential confounders, including smoking; alcohol, coffee and black tea intake; family history of breast cancer; physical activity; and intake of soy and dark green vegetables. While both green tea and soy intake had significant, independent protective effects on breast cancer risk, the benefit of green tea was primarily observed among subjects who were low soy consumers. Similarly, the protective effect of soy was primarily observed among subjects who were nondrinkers of green tea. In summary, our results point to an important role of both green tea and soy intake in relation to breast cancer risk in Asian-American women.

Adult↗

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.

Age Distribution↗