Cohort studies in Europe, but not in North-America, showed an association between exposure to outdoor particulate matter with aerodynamic diameter ≤10 μm (PM10) and lung cancer risk. Only a ...case-control study on lung cancer and PM10 in South Korea has so far been performed. For the first time in Europe we analyzed quantitatively this association using a case-control study design in highly polluted areas in Italy.
The Environment And Genetics in Lung cancer Etiology (EAGLE) study, a population-based case-control study performed in the period 2002-2005 in the Lombardy Region, north-west Italy, enrolled 2099 cases and 2120 controls frequency-matched for area of residence, gender, and age. For this study we selected subjects with complete active and passive smoking history living in the same municipality since 1980 until study enrollment. Fine resolution annual PM10 estimates obtained by applying land use regression modeling to satellite data calibrated with fixed site monitor measurements were used. We assigned each subject the PM10 average estimates for year 2000 based on enrollment address. We used logistic regression models to calculate odds ratios (OR) and 95% confidence intervals (CI) adjusted for matching variables, education, smoking, and dietary and occupational variables.
We included 3473 subjects, 1665 cases (1318 men, 347 women) and 1808 controls (1368 men, 440 women), with PM10 individual levels ranging from 2.3 to 53.8 μg/m3 (mean: 46.3). We found increasing lung cancer risk with increasing PM10 category (P-value for trend: 0.04). The OR per 10 μg/m3 was 1.28 (95% CI: 0.95-1.72). The association appeared stronger for squamous cell carcinoma (OR 1.44, 95% CI: 0.90-2.29).
In a population living in highly polluted areas in Italy, our study added suggestive evidence of a positive association between PM10 exposure and lung cancer risk. This study emphasizes the need to strengthen policies to reduce airborne pollution.
Therapy-related acute myeloid leukemia (tAML) is a rare but highly fatal complication of cytotoxic chemotherapy. Despite major changes in cancer treatment, data describing tAML risks over time are ...sparse. Among 426 068 adults initially treated with chemotherapy for first primary malignancy (9 US population-based cancer registries, 1975-2008), we identified 801 tAML cases, 4.70 times more than expected in the general population (P < .001). Over time, tAML risks increased after chemotherapy for non-Hodgkin lymphoma (n = 158; Poisson regression Ptrend < .001), declined for ovarian cancer (n = 72; Ptrend < .001), myeloma (n = 62; Ptrend = .02), and possibly lung cancer (n = 65; Ptrend = .18), and were significantly heterogeneous for breast cancer (n = 223; Phomogeneity = .005) and Hodgkin lymphoma (n = 58; Phomogeneity = .007). tAML risks varied significantly by age at first cancer and latency and were nonsignificantly heightened with radiotherapy for lung, breast, and ovarian cancers. We identified newly emerging elevated tAML risks in patients treated with chemotherapy since 2000 for esophageal, cervical, prostate, and possibly anal cancers; and since the 1990s for bone/joint and endometrial cancers. Using long-term, population-based data, we observed significant variation in tAML risk with time, consistent with changing treatment practices and differential leukemogenicity of specific therapies. tAML risks should be weighed against the benefits of chemotherapy, particularly for new agents and new indications for standard agents.
•Coincident with major changes in cancer treatments, the occurrence of tAML has changed significantly with time.•The risks for tAML should be weighed against the benefits of chemotherapy.
Hereditary retinoblastoma (Rb) survivors have increased risk of subsequent malignant neoplasms (SMNs). Previous studies reported elevated radiotherapy (RT) -related SMN risks, but less is known about ...chemotherapy-related risks.
In a long-term follow-up study of 906 5-year hereditary Rb survivors diagnosed from 1914 to 1996 and observed through 2009, treatment-related SMN risks were quantified using cumulative incidence analyses and multivariable Cox proportional hazards regression models with age as the underlying time scale.
Nearly 90% of Rb survivors were treated with RT, and almost 40% received alkylating agent (AA) -containing chemotherapy (predominantly triethylenemelamine). Median follow-up time to first SMN diagnosis was 26.3 years. Overall SMN risk was not significantly elevated among survivors receiving AA plus RT versus RT without chemotherapy (hazard ratio HR, 1.27; 95% CI, 0.99 to 1.63). AA-related risks were significantly increased for subsequent bone tumors (HR, 1.60; 95% CI, 1.03 to 2.49) and leiomyosarcoma (HR, 2.67; 95% CI, 1.22 to 5.85) but not for melanoma (HR, 0.74; 95% CI, 0.36 to 1.55) or epithelial tumors (HR, 0.89; 95% CI, 0.48 to 1.64). Leiomyosarcoma risk was significantly increased for survivors who received AAs at age < 1 (HR, 5.17; 95% CI, 1.76 to 15.17) but not for those receiving AAs at age ≥ 1 year (HR, 1.75; 95% CI, 0.68 to 4.51). Development of leiomyosarcoma was significantly more common after AA plus RT versus RT (5.8% v 1.6% at age 40 years; P = .01).
This comprehensive quantification of SMN risk after chemotherapy and RT among hereditary Rb survivors also demonstrates an AA-related contribution to risk. Although triethylenemelamine is no longer prescribed, our findings warrant further follow-up to investigate potential SMN risks associated with current chemotherapies used for Rb.
Dysplastic nevi and melanoma Goldstein, Alisa M; Tucker, Margaret A
Cancer epidemiology, biomarkers & prevention
22, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Dysplastic nevi are described as being on a continuum between common acquired nevi and melanoma because they are morphologically and biologically intermediate between these 2 entities. Since ...initially being reported as histologic lesions observed in melanoma-prone families, there has been considerable debate about the definition of dysplastic nevi, the histologic and clinical criteria used to define them, and their biologic importance. Their role as precursor lesions for melanoma is not their primary role in their relationship to melanoma because of the rarity of transformation of any individual nevus to a melanoma. Although there is still no single, universally agreed upon histologic or clinical definition or even name for these nevi, dysplastic nevi should be considered important because of their association with an increased risk for melanoma.
Population-based estimates of absolute risk of lung cancer recurrence, and of mortality rates after recurrence, can inform clinical management.
We evaluated prognostic factors for recurrences and ...survival in 2098 lung cancer case patients from the general population of Lombardy, Italy, from 2002 to 2005. We conducted survival analyses and estimated absolute risks separately for stage IA to IIIA surgically treated and stage IIIB to IV non-surgically treated patients.
Absolute risk of metastases exceeded that of local recurrence in every stage and cell type, highlighting the systemic threat of lung cancer. In stage I, the probability of dying within the first year after diagnosis was 2.7%, but it was 48.3% within first year after recurrence; in stage IV, the probabilities were 57.3% and 80.6%, respectively. Over half the patients died within one year of first metastasis. Although in stages IA to IB about one-third of patients had a recurrence, stage IIA patients had a recurrence risk (61.2%) similar to stage IIB (57.9%) and IIIA (62.8%) patients. Risk of brain metastases in stage IA to IIIA surgically treated non-small cell lung cancer patients increased with increasing tumor grade. Absolute risk of recurrence was virtually identical in adenocarcinoma and squamous cell carcinoma patients.
This population-based study provides clinically useful estimates of risks of lung cancer recurrence and mortality that are applicable to the general population. These data highlight the need for more effective adjuvant treatments overall and within specific subgroups. The estimated risks of various endpoints are useful for designing clinical trials, whose power depends on absolute numbers of events.
Melanoma epidemiology Tucker, Margaret A
Hematology/oncology clinics of North America,
06/2009, Letnik:
23, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Melanoma is a complex, heterogeneous cancer that continues to increase in incidence. Multiple studies have consistently identified major host and environmental risk factors for melanoma. Nevi, ...particularly dysplastic nevi, confer much higher risks than most pigmentary characteristics. Ultraviolet radiation exposure is the predominant environmental risk factor for melanoma. Recently, both rare high risk susceptibility genes and common polymorphic genes contributing to melanoma risk have been identified.
The molecular drivers that determine histology in lung cancer are largely unknown. We investigated whether microRNA (miR) expression profiles can differentiate histologic subtypes and predict ...survival for non-small cell lung cancer.
We analyzed miR expression in 165 adenocarcinoma and 125 squamous cell carcinoma (SQ) tissue samples from the Environment And Genetics in Lung cancer Etiology (EAGLE) study using a custom oligo array with 440 human mature antisense miRs. We compared miR expression profiles using t tests and F tests and accounted for multiple testing using global permutation tests. We assessed the association of miR expression with tobacco smoking using Spearman correlation coefficients and linear regression models, and with clinical outcome using log-rank tests, Cox proportional hazards, and survival risk prediction models, accounting for demographic and tumor characteristics.
MiR expression profiles strongly differed between adenocarcinoma and SQ (P(global) < 0.0001), particularly in the early stages, and included miRs located on chromosome loci most often altered in lung cancer (e.g., 3p21-22). Most miRs, including all members of the let-7 family, were downregulated in SQ. Major findings were confirmed by quantitative real time-polymerase chain reaction (qRT-PCR) in EAGLE samples and in an independent set of lung cancer cases. In SQ, the low expression of miRs that are downregulated in the histology comparison was associated with 1.2- to 3.6-fold increased mortality risk. A five-miR signature significantly predicted survival for SQ.
We identified a miR expression profile that strongly differentiated adenocarcinoma from SQ and had prognostic implications. These findings may lead to histology-based therapeutic approaches.
We conducted a genome-wide association study of gastric cancer and esophageal squamous cell carcinoma (ESCC) in ethnic Chinese subjects in which we genotyped 551,152 SNPs. We report a combined ...analysis of 2,240 gastric cancer cases, 2,115 ESCC cases and 3,302 controls drawn from five studies. In logistic regression models adjusted for age, sex and study, multiple variants at 10q23 had genome-wide significance for gastric cancer and ESCC independently. A notable signal was rs2274223, a nonsynonymous SNP located in PLCE1, for gastric cancer (P = 8.40 × 10−9; per-allele odds ratio (OR) = 1.31) and ESCC (P = 3.85 × 10−9; OR = 1.34). The association with gastric cancer differed by anatomic subsite. For tumors in the cardia the association was stronger (P = 4.19 × 10−15; OR = 1.57), and for those in the noncardia stomach it was absent (P = 0.44; OR = 1.05). Our findings at 10q23 could provide insight into the high incidence of both cancers in China.
Malignant melanoma of the skin (CMM) is associated with ultraviolet radiation exposure, but the mechanisms and even the wavelengths responsible are unclear. Here we use a mammalian model to ...investigate melanoma formed in response to precise spectrally defined ultraviolet wavelengths and biologically relevant doses. We show that melanoma induction by ultraviolet A (320-400 nm) requires the presence of melanin pigment and is associated with oxidative DNA damage within melanocytes. In contrast, ultraviolet B radiation (280-320 nm) initiates melanoma in a pigment-independent manner associated with direct ultraviolet B DNA damage. Thus, we identified two ultraviolet wavelength-dependent pathways for the induction of CMM and describe an unexpected and significant role for melanin within the melanocyte in melanomagenesis.
PDF
