Standardized Incidence Ratios For Lung Cancer Research Articles

No Excess Risk of Second Malignancies in Chronic Myeloid Leukemia (CML) Patients Treated with Tyrosine Kinase Inhibitors (TKIs)

Introduction With the introduction of tyrosine kinase inhibitors (TKI), the outcomes of patients with chronic myeloid leukemia (CML) has improved dramatically, with the majority of patients in chronic phase achieving near normal life expectancy. As pts live longer on TKIs, they may be more susceptible to subsequent malignancies either as late effects of TKI treatment, or due to genomic instability from having an established hematologic malignancy. Theoretical mechanisms of TKI carcinogenesis include impaired DNA repair mechanisms, inhibition of T-lymphocytes or impaired differentiation of peripheral blood progenitor cells. In this study, we evaluated the risk of subsequent cancers in CML pts at the population level and compared the effect of treatment period (pre- and post-TKI era) on that risk. Methods We used the April 2017 release of all 18 registries of the Surveillance, Epidemiology and End Results (SEER) program of the National Cancer Institute to assemble the study cohort. Only patients with CML, not otherwise specified or BCR/ ABL-positive CML were included in the analysis. Patients aged >20 years who had CML as a first cancer diagnosed between January 1973 and December 2013 who developed second cancers (excluding myeloid neoplasms and acute lymphocytic leukemia [to avoid misclassification with CML in blast crisis] and non-melanoma skin cancer) were studied. CML pts with third and subsequent cancers were excluded. Pt and disease characteristics including sex, race and ethnicity, age at diagnosis, year of diagnosis, and year of last follow-up or death were collected. Standardized incidence ratios (SIR) were calculated to assess the risk of a second malignancy by dividing the number of observed second malignancies in CML pts with the number of expected malignancies in the US population, using SEER*Stat. SIRs for the five most common second cancer types were analyzed by treatment eras (1973-1985 [era 1, in which busulfan and hydroxyurea predominated], 1986-2000 [era 2, in which interferon and hematopoietic cell transplantation predominated] and 2001-2014 [era 3, the TKI era] per Blood. 2011; 117(3):755-63 and by age groups (20-39 yrs; 40 -60 yrs and > 60 yrs). Results Of 26,810 patients diagnosed with CML between 1973 and 2014, 1,324 (4.94%) developed a subsequent cancer. The prevalence of second malignancies was 4.59% in era 1, 5.35% in era 2, and 4.84% in era 3 (with the increase from era 1 to 2 likely due to improved capture of cancers and possible transplant effects (BBMT 2007: 13(10):1121-1134)). The most common second cancers in the study period were prostate (17.98%), lung and bronchus (16.01%), breast (8.31%), urinary bladder (5.36%) and non-Hodgkin lymphoma (4.38%) with distribution by treatment era shown in Figure 1. The majority of subsequent malignancies occurred in Caucasians (85.95%), males (61.25%) and in pts > 60 years (68.43%). Table 1 shows SIR of second cancers by treatment eras. In era 1, an excess risk for bladder cancer was observed compared to matched population controls without CML (SIR 2.04, 95% CI 1.14-3.37). In era 2, SIRs for lung cancer and non-Hodgkin lymphoma were marginally elevated [1.34 (95% CI 1.03-1.72) and 1.81 (95% CI 1.01-2.98)], respectively. No excess risk of subsequent cancers was detected in the TKI era. Differences in excess risk of second cancers compared to matched population controls without CML were observed in the study period (1973-2014) when analyzed by age groups, as shown in table 2. Excess risk of oral (SIR 28.46, 95% CI 5.87-83.18) and cervical cancers (SIR 7.61, 95% CI 2.47-17.75) was observed in 20-39 yr age group, melanoma (SIR 1.83, 95% CI 1.02-3.02) in 40-59 yr age cohort, and lung and bronchus (SIR 1.31, 95% CI 1.07-1.58) and non-Hodgkin lymphoma (SIR 2.13, 95% CI 1.43-3.06) in patients >60 yrs. Conclusions In the TKI era of treatment for CML, there does not appear to be an excess risk of second cancers compared to what is seen in matched population controls without CML. Types of second cancers differ by age group. The paucity of second cancers may contribute to the survival of CML patients treated with TKIs approaching that of the general population. Download : Download high-res image (278KB) Download : Download full-size image Disclosures Advani: Pfizer: Consultancy; Takeda/ Millenium: Research Funding. Gerds: CTI BioPharma: Consultancy; Incyte: Consultancy. Maciejewski: Alexion Pharmaceuticals, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Speaker Fees; Apellis Pharmaceuticals: Consultancy; Ra Pharma: Consultancy. Majhail: Sanofi: Honoraria; Anthem, Inc.: Consultancy. Sekeres: Celgene: Membership on an entity's Board of Directors or advisory committees.

Increased Incidence of Lung Cancer Among Patients With Superficial Transitional Cell Carcinoma: A Potential Risk Cohort for Lung Cancer Screening

BackgroundSmoking is a major risk factor for lung cancer (LC) and transitional cell carcinoma of the bladder (TCC). Current recommendations for LC screening do not include TCC as a risk factor for determining screening eligibility. In this study we aimed to evaluate whether TCC patients constitute a population who might benefit from LC screening. Patients and MethodsThe Surveillance, Epidemiology, and End Results 18 database was used to determine the incidence, standardized incidence ratio (SIR), and the average time to diagnosis of LC in patients with localized TCC of the bladder (American Joint Committee on Cancer, sixth edition, stages 0-1). ResultsOn the basis of 91,606 patients with localized TCC, The SIR for LC in men was 1.89 (95% confidence interval [CI], 1.8-1.97), significantly different from the risk for all solid tumors. The SIR for LC in women was 2.43 (95% CI, 2.22-2.65), significantly higher than for men. The 5-year incidence of LC was 3.2%, and the 10-year incidence was 5.94%. The average time to diagnosis of LC was 3.4 years, with >80% of LC cases occurring within 5 years of TCC diagnosis. ConclusionPatients with localized TCC have a higher incidence of LC than the general population. The risk is significantly increased among women compared with men. Considering this increased risk, patients with early stage TCC might stand to benefit from LC screening. Additional differences were noted between male and female TCC patients, which bear further study.

Cancer incidence in a cohort of asbestos-exposed workers undergoing health surveillance.

To compare a local cohort of 2488 men occupationally exposed to asbestos and enrolled in a public health surveillance program with the 1995-2009 cancer incidence of the general population of Friuli Venezia Giulia (FVG) region, Northeast Italy, we conducted a historical cohort study. Standardized incidence ratios (SIRs), with 95% confidence interval (95% CI), for specific cancer sites were estimated in the cohort and in subgroups of workers employed in shipbuilding between 1974 and 1994. For internal comparisons, we calculated incidence rate ratios (IRRs) for all cancers, lung cancer and mesothelioma, by level of exposure to asbestos and sector of employment adjusted for smoking habits and age at start of follow-up. Among cohort members the SIR was 8.82 (95% CI 5.95-12.61) for mesothelioma and 1.61 (95% CI 1.26-2.04) for lung cancer. In subgroup analyses, the SIR for lung cancer in subjects hired in shipbuilding between 1974 and 1984 was 2.09 (95% CI 1.32-3.13). In the overall cohort, a borderline increased incidence was also found for stomach cancer (SIR = 1.53 95% CI 0.96-2.31). Internal comparisons within the cohort show that among men with high asbestos exposure level the relative risk was almost threefold for lung cancer (IRR = 2.94 95% CI 1.01-8.57). This cohort experienced an excess in the incidence of both mesothelioma and lung cancer, showing increasing incidence rates at higher level of asbestos exposure. For lung cancer, the relative incidence was highest among workers hired in shipbuilding between 1974 and 1984.

P1.01-027 Increased Risk of Lung Cancer among Women with Superficial TCC: A Potential Risk Cohort for Lung Cancer Screening

Screening for lung cancer is recommended among heavy current or former smokers at age 55-80. Transitional Cell Carcinoma of the Bladder (TCC) and lung cancer share same risk factors, however the existence of TCC is not indicated as a reason for screening for lung cancer. Patients with invasive TCC undergo full staging and therefore lung cancer is usually detected if it co-exists. However, in superficial TCC, lung evaluation is not routinely done and may be missed. Here, we have studied the incidence of lung cancer among low stage bladder cancer patients aiming to evaluate if this can be defined as a population at risk. The SEER (Statistics, Epidemiology and End Results) database was used to determine the Incidence and standardized incidence ratio (SIR), and the average time to discovery of lung cancer in Patients with localized TCC of the bladder (AJCC 6 stages T0 through T1a2) in years 2000-2013, stratified by age and gender, and compare them to the SIR for all solid tumors. Based on 89691 patients (F:M ratio 1:3.3), the SIR for all solid tumors was 1.95[CI95%:1.87-2.04] for women and 1.87[1.83-1.9] for men. The SIR for lung cancer in women was significantly higher, 2.40[2.19-2.62], with significance persisting among all age groups >50y. The SIR for men was 1.81[1.73-1.9], not significantly different from the risk for all solid tumors in any age group. The median latency period until discovery of lung cancer was 5.41, 3.54, 2.74 and 0.08 years in women, and 4.41, 3.59, 2.96 and 0.96 in men, for age groups 50-59, 60-69, 70-79 and 80+, respectively. Incidence of lung cancer is higher in localized TCC patients than among the general population, and among women it appears to be significantly higher than the general risk of solid tumors. Early stage TCC patients may therefore stand to gain from lung cancer screening, and should be considered as potential screening candidates.

Cancer incidence among Minnesota taconite mining industry workers

PurposeTo evaluate cancer incidence among Minnesota taconite mining workers. MethodsWe evaluated cancer incidence between 1988 and 2010 in a cohort of 40,720 Minnesota taconite mining workers used between 1937 and 1983. Standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) were estimated by comparing numbers of incident cancers with frequencies in the Minnesota Cancer Surveillance System. SIRs for lung cancer by histologic subtypes were also estimated. We adjusted for out-of-state migration and conducted a probabilistic bias analysis for smoking-related cancers. ResultsA total of 5700 cancers were identified, including 51 mesotheliomas and 973 lung cancers. The SIRs for lung cancer and mesothelioma were 1.3 (95% CI = 1.2–1.4) and 2.4 (95% CI = 1.8–3.2), respectively. Stomach, laryngeal, and bladder cancers were also elevated. However, adjusting for potential confounding by smoking attenuated the estimates for lung (SIR = 1.1, 95% CI = 1.0–1.3), laryngeal (SIR = 1.2, 95% CI = 0.8–1.6), oral (SIR = 0.9, 95% CI = 0.7–1.2), and bladder cancers (SIR = 1.0, 95% CI = 0.8–1.1). ConclusionsTaconite workers may have an increased risk for certain cancers. Lifestyle and work-related factors may play a role in elevated morbidity. The extent to which mining-related exposures contribute to disease burden is being investigated.

Liver Transplantation-Associated Lung Cancer: Comparison of Clinical Parameters and Outcomes

BackgroundThe incidence of lung cancer (LC) is increased in patients with a history of liver transplantation (LT). The purpose of our study was to compare the clinical characteristics and outcomes of patients with postliver transplantation LC (PLTLC) with cohorts of patients with “transplant-naive” LC, and LT patients without LC. Patients and MethodsAll the patients who had undergone LT or had been diagnosed with LC from 1987 to 2012 were included in the present analysis. The PLTLC cohort was compared with a LT cohort (n = 725) and the local LC registry (n = 2803). The standardized incidence ratios (SIRs) were computed in the classic manner after adjustment for sex, age, and year of follow-up. ResultsWithin the LT cohort, 22 patients (5 women) developed PLTLC (2.3%). The SIR for LC in LT recipients was 4.4 in the women and 2.6 in the men. The PLTLC cohort was older at LT (58.4 vs. 53.3 years; P = .028). Also, 90.5% of the PLTLC group had a history of smoking; 8 patients (42.1%) had had LC detected by annual routine lung cancer screening. The median post-LT survival was significantly inferior in the PLTLC cohort (117.1 vs. 182.6 months; P = .041). The median overall survival (OS), starting from the diagnosis of LC, was similar in the PLTLC and LC cohort (14.7 vs. 15.1 months; P = .519). ConclusionThe incidence of LC is significantly increased in the LT population. Therefore, LC screening might be an option for LT patients with a history of smoking. The prognosis of LC does not seem to be impaired by LT, suggesting a minor effect of LT on OS in patients with lung cancer.

Increased risk of lung cancer associated with occupational exposure to benzidine and/or beta-naphthylamine.

To evaluate non-urological cancer risks associated with benzidine (BZ) and beta-naphthylamine (BNA), a historical cohort study was undertaken. A total of 224 male workers exposed to BZ/BNA from a single factory were followed from 1953 to 2011. To estimate BZ/BNA exposure dose, duration of exposure (DOE) was defined as duration of employment between 1953 and 1972, the period when BZ and BNA were produced and used at this factory. Subjects were dichotomized (into long- and short-term groups) based on the median of DOE. Cancer-specific standardized incidence ratios (SIRs) were calculated using national and regional incidence rates as reference. Smoking history was obtained through questionnaires and other sources. Association between lung cancer (LC) or bladder cancer (BC) incidence and DOE was assessed using Cox's proportional hazards model. Vital status follow-up was successful for 216 (96.4%). Follow-up duration averaged 44.0 (SD 10.7) years. Increased SIRs based on national rates were found for all cancers (81 cases, SIR = 1.58, 95% CI 1.26-1.98), LC (18 cases, SIR = 2.58, 95% CI 1.53-4.07), and BC (7 cases, SIR = 4.70, 95% CI 1.89-9.67). Among workers with >20 years after first exposure, the SIR for LC was statistically elevated in the long DOE group (15 cases, SIR = 3.34, 95% CI 1.87-5.51). After adjustment for smoking, exposure to bis(chloromethyl) ether, and age at first exposure, a marginally significant hazard ratio (HR) was observed for the long DOE group (adjusted HR = 3.02, 95% CI 0.84-10.93, p = 0.091), compared to the short DOE group. DOE did not affect BC incidence. This study confirms the high risk of LC besides BC, suggesting that BZ/BNA have the potential to cause LC.

The changing landscape of HIV‐related lung disease: Non‐AIDS lung malignancy as a player in the field

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Risk of second primary cancer after treatment for esophageal cancer: a pooled analysis of nine cancer registries

The introduction of new treatments for esophageal cancer including surgery, chemotherapy, radiotherapy, or a combination of these modalities has not only improved patient survival, but may also increase the risk of the second primary cancers. The available evidence is conflicting with most risk estimates based on sparse numbers. Here we estimated standardized incidence ratios (SIRs) of second cancer among 24,557 esophageal cancer survivors (at least 2 months) in the Surveillance, Epidemiology, and End Results (SEER) Program between 1973 and 2007, who had been followed up for median 6.5 years (range 2 months-29.3 years). Second cancer risk was statistically significantly elevated (SIR = 1.34, 95% confidence interval [CI]= 1.25-1.42) among the survivors compared with the general population; the SIRs for cancers of oral and pharynx, stomach, small intestine, larynx, lung and bronchus, thyroid and prostate cancer were 8.64 (95% CI = 7.36-10.07), 2.87 (95% CI = 2.10-3.82), 3.80 (95% CI = 1.82-7.00), 3.19 (95% CI = 2.12-4.61), 1.68 (95% CI = 1.46-1.93), 2.50 (95% CI = 1.25-4.47), and 0.77 (95% CI = 0.65-0.90), respectively. Radiotherapy raised cancer risk of larynx (SIR = 3.98, 95% CI = 2.43-6.14) and thyroid (SIR = 3.57, 95% CI = 1.54-7.03) among all esophageal cancer survivors. For patients who had 5-9 years of follow up after radiotherapy, the SIR for lung cancer was 3.46 (95% CI = 2.41-4.82). Patients with esophageal cancer are at increased risks of second cancers of oral and pharynx, larynx, lung, and thyroid, while at a decreased risk for prostate cancer. These findings indicate that radiotherapy for esophageal cancer patients may increase risk of developing second cancers of larynx, lung, and thyroid. Thus, randomized clinical trials to address the association of radiotherapy and the risk of secondary cancer are warranted.

Esophageal cancer risk among immigrants in Sweden

Esophageal squamous cell carcinoma is linked to alcohol drinking, whereas esophageal adenocarcinoma risk is increased by overweight and obesity. Both histologies are directly related to tobacco smoking. We wanted to define the risk of esophageal cancer by histology and length of stay among immigrants in Sweden. The nationwide Swedish Family Cancer database (2010 version: data on cancers originate from the nationwide Swedish Cancer Registry) was used to calculate standardized incidence ratios (SIRs) for esophageal cancer among immigrants compared with the native Swedes. SIRs for lung cancer were also calculated as a proxy for smoking prevalence. The patient series covered 5930 male and 1998 female Swedes, and 410 and 198 immigrants. The risk of esophageal cancer was increased in female Finns (SIR=1.66), Britons (3.73), and Southeast Africans (5.26), whereas male Baltic (0.44), former Yugoslavian (0.47), other Europeans (0.58), and other Asians (0.52) showed a decreased risk. The risk of squamous cell carcinoma was increased among Finns (men=1.32, women=1.90) and Iranian women (3.80), whereas Danish men (1.66) had an increased risk of adenocarcinoma. No trend was observed for the risks in immigrants according to the length of stay. We found no covariation between the birth region-specific SIRs for squamous cell carcinoma and lung cancer. Early childhood exposures or preservation of original habits might be the main environmental exposures influencing squamous cell carcinoma risks in some immigrants. The increased risk of adenocarcinoma among Danish men may confirm the role of obesity in adenocarcinoma risk.

Lung cancer mortality risk among breast cancer patients treated with anti‐estrogens

The Women's Health Initiative randomized clinical trial reported that menopausal hormone therapy increases lung cancer mortality risk. If this is true, use of anti-estrogens should be associated with decreased lung cancer mortality risk. The authors compared lung cancer incidence and mortality among breast cancer patients with and without anti-estrogen therapy. Our study included all 6655 women diagnosed with breast cancer between 1980 and 2003 and registered at the Geneva Cancer Registry. Among these women, 46% (3066) received anti-estrogens. All women were followed for occurrence and death from lung cancer until December 2007. The authors compared incidence and mortality rates among patients with and without anti-estrogens with those expected in the general population by Standardized Incidence Ratios (SIRs) and Standardized Mortality Ratios (SMRs). After a total of 57,257 person-years, 40 women developed lung cancer. SIRs for lung cancer were not significantly decreased among breast cancer patients with and without anti-estrogens (0.63, 95% confidence intervals [CI], 0.33-1.10; and 1.12, 95% CI, 0.74-1.62, respectively) while SMR was decreased among women with anti-estrogens (0.13, 95% CI, 0.02-0.47, P<.001) but not for women without anti-estrogens (0.76, 95% CI, 0.43-1.23). Compared with expected outcomes in the general population, breast cancer patients receiving anti-estrogen treatment for breast cancer had lower lung cancer mortality. This study further supports the hypothesis that estrogen therapy modifies lung cancer prognosis.

Cancer incidence in a petrochemical industry area in Sweden

Emissions from petrochemical industries may contain suspected or established carcinogens. As increased incidence of cancer in residential areas close to petrochemical industries has been reported in the literature, we conducted a study of cancer incidence in Stenungsund, Sweden, where petrochemical industries were established in the mid1960s. A number of cancer cases in the central parts of Stenungsund were collected from the regional cancer registry for each year between 1974 and 2005. In addition to the total number of cases, the numbers of leukemia, lymphoma, liver cancer, lung cancer, and brain cancer were also collected. Expected numbers for each year were calculated based on age- and sex-specific incidence rates in reference areas. Levels of carcinogenic volatile hydrocarbons (VOC) were estimated from measurements and emission data. A dispersion model was used to classify Stenungsund into a “low” and “high” ethylene level area. Standardized Incidence Ratio (SIR) for all cancer for the entire period was 1.02 (95% CI 0.97–1.08). The occurrence of leukemia, lymphoma, and cancer in the central nervous system was slightly lower than expected for the entire period. SIR for lung cancer was 1.37 (95% CI 1.10–1.69), and SIR for liver cancer was 1.50 (0.82–2.53). VOC levels were low. Taking estimated exposure and demographic factors into account, our assessment is that occurrence of cancer was not affected by industrial emissions in any of the studied sites.

Risk of transitional-cell carcinoma of the bladder in first- and second-generation immigrants to Sweden

Environmental risk factors, particularly tobacco smoking, are important for transitional-cell carcinoma of the bladder. Studies in migrants may provide valuable insight into the environmental and genetic etiology of cancer. The nationwide Swedish Family-Cancer Database was used to calculate standardized incidence ratios (SIRs) for transitional-cell carcinoma among the immigrants compared with native Swedes. SIRs for lung cancer were also calculated as a proxy for smoking prevalence. Significantly decreased risks of bladder cancer were observed for male (SIR=0.89) and female (0.71) Finns and male East Asian (0.39) first-generation immigrants. Male immigrants from many countries showed increased risks, ranging from 1.18 to 2.29. Only female immigrants from Denmark (1.40) and Norway (1.27) had increased risks. The risks for bladder and lung cancers correlated, except for Finnish and Iranian men. The sons of immigrants born in high-risk countries had an increased SIR (1.51) whereas the daughters of immigrants born in low-risk countries had a decreased risk (0.32). The risk in the second-generation immigrants born in Sweden was equal to that of natives. In conclusion, the observed bladder cancer risks in the first-generation immigrants, the changes in risks in the second-generation immigrants, and the covariation of the risk patterns of bladder and lung cancers suggested a main contribution by tobacco smoking. The exceptional patterns among the Finns and Iranians may point to the existence of modifying factors. The changes in incidence in second-generation immigrants, yet based on small case numbers, lend little support to the involvement of genetic factors.

Incidence of cancer among patients with systemic sclerosis in Korea: results from a single centre

Objective: The aim of this study was to determine whether the incidence of cancer has increased among patients with systemic sclerosis (SSc) in Korea.Methods: The study subjects consisted of 112 patients who had been consecutively evaluated for at least 6 months between 1990 and 2007. We retrospectively reviewed their medical records, investigated the incidence rate of cancer and compared it with that of the Korea National Cancer Centre database.Results: Nine out of 112 patients developed cancer (four males and five females). The average age at diagnosis of cancer was 56.4 years and the mean disease duration was 8.9 years. The standardized incidence ratio (SIR) for SSc patients was 4.2 [95% confidence interval (CI) 2.3–6.1], 3.7 for women (95% CI 1.2–6.2) and 6.4 for men (95% CI 1.6–11.2). Lung cancer was the most common cancer (n = 4), followed by oesophagus (n = 1), stomach (n = 1), liver (n = 1), pancreas (n = 1), and squamous cell carcinoma of unknown origin (n = 1). All patients who developed lung cancer were female and non‐small cell carcinoma in origin. The SIR of lung cancer in female patients was 23.0 (95% CI 6.0–40.0). Two out of four lung cancer patients had concomitant interstitial lung disease (ILD); all were non‐smokers. Treatment agents, autoantibodies, smoking, and lung involvement were not significantly different between SSc patients with or without cancer.Conclusion: The SIR of cancer was significantly higher in SSc patients, and especially in those who were male, than in the general population. Lung cancer was the most common cancer. Active surveillance for the detection of cancer should be performed in all SSc patients.

Risk of Second Lung Cancer in Chronic Lymphocytic Leukemia.

Background: Studies have shown that patients with chronic lymphocytic leukemia (CLL) are at increased risk of developing second lung cancer. The underlying mechanisms for this increased risk have yet not been identified. Risk factors may differ between histological lung cancer subtypes. However, though relevant to the clarification of the association between the two malignancies, little is known about the lung cancer subtype distribution in CLL patients.Methods: We investigated the occurrence of second lung cancer overall and its major histological subtypes in all patients diagnosed with CLL in Denmark between 1943 and 1999 in a retrospective registry-based cohort study. The relative risk was expressed as the standardized incidence ratio (SIR), i.e. the ratio of the observed to the expected number of lung cancer cases, based on age-, sex-, and calendar year specific incidence rates for the Danish population, available from the Danish Cancer Registry.Results: Overall, 9,541 patients diagnosed with CLL between 1943 and 1999 were followed for lung cancer occurrence. The median age at onset was 70 years and the male-to-female ratio was 1.6. Second lung cancer occurred in 147 patients (122 men and 25 women) during 36,604 person-years of follow-up (median 2.5 years) corresponding to a statistically significantly increased relative risk (SIR=1.83, 95% CI 1.55–2.15). There was no difference in risk between women and men (phom=0.27). The relative risk for lung cancer varied slightly by age at CLL being particularly high in younger age groups (≤59 years SIR=2.18 (1.53–3.10), 60–69 years SIR=2.26 (1.78–2.86), 70–79 years SIR=1.28 (0.93–1.76), ≥80 years SIR=1.51 (0.79–2.90); phom=0.02). In contrast, SIR for lung cancer did not vary by time since CLL diagnosis (phom=0.64). In 95 cases (72 men, 23 women) of second lung cancer information about major histological subtypes were available. We found a statistically significantly elevated risk for all major subtypes, except small-cell carcinoma (adenocarcinoma SIR=2.85 (2.04–3.99), large-cell carcinoma SIR=2.31 (1.04–5.15), squamous cell carcinoma SIR=2.30 (1.68–3.14), small cell carcinoma SIR=1.47 (0.90–2.39)).Discussion: In one of the largest and most detailed register-based cohort studies so far, we found an increased occurrence of lung cancer among CLL patients, which was apparent for major lung cancer subtypes. While increased medical surveillance of the CLL patients cannot be ruled out as explanation for the increased risk, the uniform distribution over time since CLL diagnosis suggests that it is unrelated to initial therapy. Tobacco smoking is the major risk factor in lung cancer. Data on smoking history were not available in our study, however, previous studies suggest that smoking is not associated with CLL. Family aggregation found for both lung cancer and CLL may indicate hereditary predisposition to the two conditions. Furthermore, individual susceptibility to malignant diseases may be influenced by polymorphisms in enzymes metabolizing carcinogenes, suggested independently for CLL and lung cancer. Given the prolonged survival of patients with CLL, further studies are needed to address the causal relationship between CLL and second malignancies, including lung cancer.

Cancer incidence among members of the Norwegian trade union of insulation workers.

Insulation work has been described as an occupation with high exposure to asbestos. A cohort of members of the Norwegian Trade Union of Insulation Workers (n = 1116), hired between 1930 and 1975, was established. During 2002, the cohort was linked to the Cancer Registry of Norway. The standardized incidence ratio (SIR) of pleural mesothelioma was 12.9 (95% confidence interval [CI] = 6.0-24.6). Two cases with peritoneal mesotheliomas were found (SIR, 14.8; 95% CI = 1.8-53.4). The SIR of lung cancer was 3.0 (95% CI = 2.3-3.8). Four cases of lung cancer were observed among cork workers without any exposure to asbestos, but to cork dust and tar smoke (SIR, 5.3; 95% CI = 1.5-13.6). Our study showed a high risk of mesothelioma and an elevated risk of lung cancer among members of the Trade Union of Insulation Workers.

Decreased cancer risk in patients who have been operated on with total hip and knee arthroplasty for primary osteoarthrosis: a meta-analysis of 6 Nordic cohorts with 73,000 patients.

3 Nordic cohorts of total hip (THA) and total knee arthroplasty (TKA) in patients operated on for primary osteoarthrosis during 1967-1995 were partly adapted and combined for meta-analysis. THA was performed in 49,000 patients and TKA in 24,000 totaling 497,000 person years. The mean and maximum follow-up times were 6.8 and 30 years, respectively. Standardized incidence ratios (SIRs) with 95% confidence intervals (95% CI) were calculated for the observed and expected number of cancers. The expected numbers were based on national incidence rates. The overall SIRs as well as the site-specific ones were similar in the THA and TKA patients. The observed number of cancers at all sites was 7,639 and the expected one was 8,202 (SIR 0.93, 95% CI 0.91-0.95). The SIRs for lung cancer (0.69, 0.64-0.75) and laryngeal cancer (0.64, 0.44-0.92) were reduced. The incidence was also low for cancers of the stomach (SIR 0.76, 0.67-0.84), colon (SIR 0.86, 0.79-0.93) and rectum (SIR 0.89, 0.80-0.98). Among TKA patients, the only increases in SIRs were seen in cancers of the endometrium (SIR 1.36, 1.05-1.74), prostate (SIR 1.19, 1.02-1.38) and, among both THA and TKA patients, in skin melanoma (combined SIR 1.21, 1.03-1.41).

Decreased cancer risk in patients who have been operated on with total hip and knee arthroplasty for primary osteoarthrosis

3 Nordic cohorts of total hip (THA) and total knee arthroplasty (TKA) in patients operated on for primary osteoarthrosis during 1967–1995 were partly adapted and combined for meta-analysis. THA was performed in 49,000 patients and TKA in 24,000 totaling 497,000 person years. The mean and maximum follow-up times were 6.8 and 30 years, respectively. Standardized incidence ratios (SIRs) with 95% confidence intervals (95% CI) were calculated for the observed and expected number of cancers. The expected numbers were based on national incidence rates. The overall SIRs as well as the site-specific ones were similar in the THA and TKA patients. The observed number of cancers at all sites was 7,639 and the expected one was 8,202 (SIR 0.93,95% CI 0.91–0.95).The SIRs for lung cancer (0.69, 0.64–0.75) and laryngeal cancer (0.64, 0.44–0.92) were reduced. The incidence was also low for cancers of the stomach (SIR 0.76, 0.67–0.84), colon (SIR 0.86, 0.79–0.93) and rectum (SIR 0.89, 0.80–0.98).Among TKA patients, the only...

Progression of Asbestosis Predicts Lung Cancer

To explore whether the progression of asbestosis correlates with the risk of lung cancer among patients with asbestosis. A group of 85 asbestosis patients (78 men and 7 women) were radiographically followed up between 1979 and 1987. Two or three posteroanterior radiographs taken from each patient in 1978 to 1979, 1983 to 1984, and 1986 to 1987 were classified according to the International Labour Office 1980 classification and were used to divide the patients into progressors and nonprogressors. Follow-up for cancer was done automatically through the files of the Finnish Cancer Registry from the time of determination of the progression status to December 31, 1994. Predictors of lung cancer risk were studied with a logistic regression model, and the standardized incidence ratio (SIR) was calculated for lung cancer. Of the 24 male patients with progressive small opacity profusion, 11 (46%) developed lung cancer, as opposed to 5 (9%) of the 54 male patients without progression. The SIR for lung cancer was 37 (95% confidence interval, 18 to 66) for the progressors and 4.3 (1.4 to 9.9) for the nonprogressors. In both groups, all the lung cancer cases occurred among smokers or ex-smokers. None of the seven female patients showed progressive small opacity profusion. One of them developed lung cancer. In the logistic regression model including all 85 asbestosis patients, radiographic progression of small opacity profusion (p=0.0009) and current smoking (0.0021) were significant predictors of lung cancer morbidity. Asbestosis patients with radiographic progression of small opacity profusion over a few years are at a higher risk of lung cancer than those with a less aggressive course of the disease. The progression of pulmonary fibrosis may be an independent risk factor that, in addition to smoking history and the intensity of asbestos exposure, could be used to estimate lung cancer risk.

Incidence of invasive cancers following basal cell skin cancer.

To obtain quantitative information on the risk of invasive cancers following a diagnosis of basal cell carcinoma (BCC) of the skin, patients with incident BCC cases listed in the cancer registries of the Swiss cantons of Vaud and Neuchâtel between 1974 and 1994 were actively followed up through December 31, 1994, for the occurrence of subsequent invasive neoplasms. Among 11,878 persons with incident BCC who were followed for a total of 76,510 person-years at risk, 1,543 metachronous cancers were observed versus 1,397.9 expected, corresponding to a standardized incidence ratio (SIR) of 1.1 (95% confidence interval (CI) 1.0-1.2). However, after exclusion of skin cancers (mostly squamous cell carcinoma and melanoma), 975 second primary cancers were observed versus 1,059 expected (SIR = 0.9, 95% CI 0.8-1.0). Significant excesses were registered for cancer of the lip (SIR = 2.2), for squamous cell skin cancer (SIR = 4.5) and melanoma of the skin (SIR = 2.5), and for non-Hodgkin's lymphoma (SIR = 1.9). The SIRs were also above unity, though not significantly, for cancers of the salivary glands (SIR = 2.8) and the small intestine (SIR = 2.1) and for soft-tissue sarcomas (SIR = 1.7). The SIR for lung cancer was 0.9. The SIRs for salivary gland and skin cancer were appreciably greater below age 70 years. For most sites, particularly for squamous cell cancer and melanoma of the skin, the SIRs remained elevated 5 or more years after BCC diagnosis. The cumulative incidence of squamous cell skin cancer was 13% at 19 years; this stresses the importance of carefully monitoring skin lesions among persons previously diagnosed with BCC.