Publications by authors named "Sara J Schonfeld"

43 Publications

Benign Tumors in Long-Term Survivors of Retinoblastoma.

Cancers (Basel) 2021 Apr 8;13(8). Epub 2021 Apr 8.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA.

Hereditary retinoblastoma survivors have substantially increased risk of subsequent malignant neoplasms (SMNs). The risk of benign neoplasms, a substantial cause of morbidity, is unclear. We calculated the cumulative incidence of developing benign tumors at 60 years following retinoblastoma diagnosis among 1128 hereditary (i.e., bilateral retinoblastoma or unilateral with family history, mutation testing was not available) and 924 nonhereditary retinoblastoma survivors diagnosed during 1914-2006 at two US medical centers with follow-up through 2016. Using Cox proportional hazards regression, we compared benign tumor risk by hereditary status and evaluated the association between benign tumors and SMNs. There were 100 benign tumors among 73 hereditary survivors (cumulative incidence = 17.6%; 95% confidence interval [CI] = 12.9-22.8%) and 22 benign tumors among 16 nonhereditary survivors (cumulative incidence = 3.9%; 95%CI = 2.2-6.4%), corresponding to 4.9-fold (95%CI = 2.8-8.4) increased risk for hereditary survivors. The cumulative incidence after hereditary retinoblastoma was highest for lipoma among males (14.0%; 95%CI = 7.7-22.1%) and leiomyoma among females (8.9%; 95%CI = 5.2-13.8%). Among hereditary survivors, having a prior SMN was associated with 3.5-fold (95%CI = 2.0-6.1) increased risk of developing a benign tumor; the reciprocal risk for developing an SMN after a benign tumor was 1.8 (95%CI = 1.1-2.9). These large-scale, long-term data demonstrate an increased risk for benign tumors after hereditary versus nonhereditary retinoblastoma. If confirmed, the association between benign tumors and SMNs among hereditary patients may have implications for long-term surveillance.
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http://dx.doi.org/10.3390/cancers13081773DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068196PMC
April 2021

Radiation-related genomic profile of papillary thyroid carcinoma after the Chernobyl accident.

Science 2021 May 22;372(6543). Epub 2021 Apr 22.

Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA.

The 1986 Chernobyl nuclear power plant accident increased papillary thyroid carcinoma (PTC) incidence in surrounding regions, particularly for radioactive iodine (I)-exposed children. We analyzed genomic, transcriptomic, and epigenomic characteristics of 440 PTCs from Ukraine (from 359 individuals with estimated childhood I exposure and 81 unexposed children born after 1986). PTCs displayed radiation dose-dependent enrichment of fusion drivers, nearly all in the mitogen-activated protein kinase pathway, and increases in small deletions and simple/balanced structural variants that were clonal and bore hallmarks of nonhomologous end-joining repair. Radiation-related genomic alterations were more pronounced for individuals who were younger at exposure. Transcriptomic and epigenomic features were strongly associated with driver events but not radiation dose. Our results point to DNA double-strand breaks as early carcinogenic events that subsequently enable PTC growth after environmental radiation exposure.
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http://dx.doi.org/10.1126/science.abg2538DOI Listing
May 2021

Risk factors for contralateral breast cancer in postmenopausal breast cancer survivors in the NIH-AARP Diet and Health Study.

Cancer Causes Control 2021 Apr 20. Epub 2021 Apr 20.

Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Purpose: The role of established breast cancer risk factors and clinical characteristics of the first breast cancer in the development of contralateral breast cancer (CBC) among postmenopausal women is unclear.

Methods: We identified 10,934 postmenopausal women diagnosed with a first primary breast cancer between 1995 and 2011 in the NIH-AARP Diet and Health Study. CBC was defined as a second primary breast cancer diagnosed in the contralateral breast ≥ 3 months after the first breast cancer. Exposures included pre-diagnosis risk factors (lifestyle, reproductive, family history) and clinical characteristics of the first breast cancer. We used multivariable Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).

Results: Over a median follow-up of 6.8 years, 436 women developed CBC. We observed an increasing trend in CBC risk by age (p-trend = 0.002) and decreasing trend by year of diagnosis (p-trend = 0.001) of the first breast cancer. Additional risk factor associations were most pronounced for endocrine therapy (HR 0.68, 95% CI 0.53-0.87) and family history of breast cancer (HR 1.38, 95% CI 1.06-1.80, restricted to invasive first breast cancer). No associations were found for lifestyle (body mass index, physical activity, smoking, alcohol) or reproductive factors (age at menarche, parity, age at first birth, age at menopause).

Conclusions: This study suggests that clinical characteristics of the first breast cancer and family history of breast cancer, but not pre-diagnosis lifestyle and reproductive factors, are strongly associated with CBC risk among postmenopausal women. Future studies are needed to understand how these factors contribute to CBC etiology and to identify further opportunities for prevention.
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http://dx.doi.org/10.1007/s10552-021-01432-2DOI Listing
April 2021

A totally 'rad' week: summary of the 2019 NCI Radiation Epidemiology and Dosimetry Course.

J Radiol Prot 2021 Mar 8;40(4):1541-1543. Epub 2021 Mar 8.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, United States of America.

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http://dx.doi.org/10.1088/1361-6498/abb03aDOI Listing
March 2021

Long-term risk of subsequent cancer incidence among hereditary and nonhereditary retinoblastoma survivors.

Br J Cancer 2021 Mar 21;124(7):1312-1319. Epub 2021 Jan 21.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.

Background: Increased sarcoma and melanoma risks after hereditary retinoblastoma are well established, whereas less is known about epithelial subsequent malignant neoplasms (SMNs) and risks for multiple (≥2) SMNs.

Methods: Leveraging long-term follow-up and detailed histologic information, we quantified incident SMN risk among 1128 hereditary and 924 nonhereditary retinoblastoma survivors (diagnosed 1914-2006; follow-up through 2016). Standardised incidence ratios (SIRs) compared cancer risk after retinoblastoma relative to the general population. We estimated cumulative incidence accounting for competing risk of death.

Results: Hereditary survivors had statistically significantly increased SMN risk (N = 239; SIR = 11.9; 95% confidence interval [CI] 10.4-13.5), with SIRs >80-fold for sarcomas, nasal cavity tumours and pineoblastoma. Significantly increased risks were also observed for melanoma and central nervous system, oral cavity and breast SMNs (SIRs = 3.1-17), but not the uterus, kidney, lung, bladder, pancreas or other types. Cumulative incidence 50 years following hereditary retinoblastoma was 33.1% (95% CI 29.0-37.2) for a first SMN and 6.0% (95% CI 3.8-8.2) for a second SMN. SMN risk was not increased after nonhereditary retinoblastoma (N = 25; SIR = 0.8; 95% CI 0.5-1.2).

Conclusion: Beyond the established sarcoma and melanoma risks after hereditary retinoblastoma, we demonstrate increased risk for a more limited number of epithelial malignancies than previously suggested. Cumulative incidence estimates emphasise long-term SMN burden after hereditary retinoblastoma.
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http://dx.doi.org/10.1038/s41416-020-01248-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007574PMC
March 2021

Racial and ethnic differences in risk of second primary cancers among prostate cancer survivors.

Cancer Causes Control 2020 Nov 24;31(11):1011-1019. Epub 2020 Aug 24.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.

Purpose: Previous studies have shown an overall decreased risk of second cancers among prostate cancer survivors, but this has not been comprehensively examined by race/ethnicity. We conducted a retrospective cohort study of 716,319 one-year survivors of prostate cancer diagnosed at ages 35-84 during 2000-2015 as reported to 17 US Surveillance, Epidemiology and End Results (SEER) registries.

Methods: We estimated standardized incidence ratios (SIRs) for second primary non-prostate malignancies by race/ethnicity (non-Latino white, Black, Asian/Pacific Islander [API] and Latino), by Gleason, and by time since prostate cancer diagnosis. Poisson regression models were used to test heterogeneity between groups with the expected number as the offset.

Results: 60,707 second primary malignancies were observed. SIRs for all second cancers combined varied significantly by race/ethnicity: SIR: 0.88 (95% confidence interval: 0.87-0.89), SIR: 0.92 (0.89-0.95), SIR: 0.97 (0.95-0.99), and SIR: 1.05 (1.01-1.09) (p-heterogeneity < 0.001). SIRs for all cancers combined were higher among survivors of higher vs. lower Gleason prostate cancers irrespective of race/ethnicity. We observed significant heterogeneity by race/ethnicity in SIRs for 9 of 14 second cancer types investigated including lung, bladder, kidney, and liver.

Conclusions: Our results confirm that most prostate cancer survivors have lower risks of second cancers than expected, but the magnitude varied by race/ethnicity. Exceptionally, API men had small but significantly increased risk. Further research to understand drivers of the observed race/ethnicity heterogeneity is warranted.
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http://dx.doi.org/10.1007/s10552-020-01336-7DOI Listing
November 2020

Occupational cohort study of current and former workers exposed to chrysotile in mine and processing facilities in Asbest, the Russian Federation: Cohort profile of the Asbest Chrysotile Cohort study.

PLoS One 2020 29;15(7):e0236475. Epub 2020 Jul 29.

Federal State Budgetary Scientific Institution "Izmerov Research Institute of Occupational Health" (IRIOH), Moscow, the Russian Federation.

A historical cohort study in workers occupationally exposed to chrysotile was set up in the town of Asbest, the Russian Federation, to study their cause-specific mortality, with a focus on cancer. Chrysotile has different chemical and physical properties compared with other asbestos fibres; therefore it is important to conduct studies specifically of chrysotile and in different geographical regions to improve the knowledge about its carcinogenicity. Setting was the town of Asbest, Sverdlovsk oblast, the Russian Federation. Participants were all current and former employees with at least one year of employment between 1/1/1975 and 31/12/2010 in the mine, enrichment factories, auto-transport and external rail transportation departments, the central laboratory, and the explosives unit of the company. Of the 35,837 cohort members, 12,729 (35.5%) had died (2,373 of them of cancer, including 10 of mesothelioma), 18,799 (52.5%) were known to be alive at the end of the observation period (2015), and 4,309 (12.0%) were censored before the end of 2015. Mean follow-up duration was 21.7 years in men and 25.9 years in women. The mean age at death was 59.4 years in men and 66.5 years in women. This is the largest occupational cohort of chrysotile workers to date, and the only one with a large proportion of exposed female workers.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0236475PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7390538PMC
September 2020

Dose-volume effects of breast cancer radiation therapy on the risk of second oesophageal cancer.

Radiother Oncol 2020 10 15;151:33-39. Epub 2020 Jul 15.

Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, United States.

Purpose: To investigate the relationship between oesophagus dose-volume distribution and long-term risk of oesophageal cancer after radiation therapy for breast cancer.

Materials And Methods: In a case-control study nested within a cohort of 289,748 ≥5-year survivors of female breast cancer treated in 1943-2003 in five countries, doses to the second primary cancer (D) and individual dose-volume histograms (DVH) to the entire oesophagus were reconstructed for 252 oesophageal cancer cases and 488 matched controls (median follow-up time: 13, range: 5-37 years). Using conditional logistic regression, we estimated excess odds ratios (EOR) of oesophageal cancer associated with DVH metrics. We also investigated whether DVH metrics confounded or modified D-related -risk estimates.

Results: Among the DVH metrics evaluated, median dose (D) to the entire oesophagus had the best statistical performance for estimating risk of all histological types combined (EOR/Gy = 0.071, 95% confidence interval [CI]: 0.018 to 0.206). For squamous cell carcinoma, the most common subtype, the EOR/Gy for D increased by 31% (95% CI: 3% to 205%) for each increment of 10% of V30 (p = 0.02). Adjusting for DVH metrics did not materially change the EOR/Gy for D, but there was a borderline significant positive interaction between D and V30 (p = 0.07).

Conclusion: This first study investigating the relationship between oesophagus dose-volume distribution and oesophageal cancer risk showed an increased risk per Gy for D with larger volumes irradiated at high doses. While current techniques allows better oesophagus sparing, constraints applied to D and V30 could potentially further reduce the risk of oesophageal cancer.
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http://dx.doi.org/10.1016/j.radonc.2020.07.022DOI Listing
October 2020

Risk of Second Primary Bone and Soft-Tissue Sarcomas Among Young Adulthood Cancer Survivors.

JNCI Cancer Spectr 2019 Sep 20;3(3):pkz043. Epub 2019 Jun 20.

Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD.

Excess sarcoma risks after childhood cancer are well established, but risks among young adulthood cancer survivors are poorly understood. Using US population-based cancer registry data, we compared bone and soft-tissue sarcoma risk vs the general population among 186 351 individuals who were diagnosed with nonsarcoma first primary malignancies at ages 20-39 years from 1975 to 2014 (follow-up through 2015) and survived at least 1 year. Bone sarcomas were rare (n = 50), but risk was statistically significantly elevated overall (2.9-fold) and greater than fivefold after Hodgkin lymphoma, non-Hodgkin lymphoma, and central nervous system tumors. Soft-tissue sarcomas were more common (n = 284) and risks were statistically significantly elevated approximately twofold overall and after melanoma and carcinomas of the breast, thyroid, and testis, and greater than fourfold after Hodgkin lymphoma and central nervous system tumors. Risks varied markedly by subtype, with the highest risks (greater than fourfold) for osteosarcoma and the soft-tissue subtypes of rhabdomyosarcoma and blood vessel and nerve sheath sarcomas. These data demonstrate elevated risk for sarcoma after a range of young adulthood cancers.
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http://dx.doi.org/10.1093/jncics/pkz043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049991PMC
September 2019

Tobacco smoking among chrysotile asbestos workers in Asbest in the Russian Federation.

Occup Environ Med 2020 09 12;77(9):623-627. Epub 2020 May 12.

Section of Environment and Radiation, International Agency for Research on Cancer (IARC), Lyon, France.

Objectives: A historical cohort study of cancer mortality is being conducted among workers in a chrysotile mine and its enrichment factories in the town of Asbest, Russian Federation. Because individual-level information on tobacco use is not available for Asbest Chrysotile Cohort members, a cross-sectional survey of smoking behaviours was conducted among active and retired workers.

Methods: Self-administered questionnaires were completed by active workers during meetings organised by occupational safety personnel. Retired workers completed questionnaires during meetings of the Veterans Council or were interviewed via telephone or in person. Of the respondents, 46% could be linked to the Asbest Chrysotile Cohort. Among those, logistic regression models were used to assess associations between smoking and cumulative dust exposure.

Results: Among men, smoking prevalence was high and relatively consistent across birth decades (average, 66%), and was similar in workers across all levels of cumulative dust exposure (p trend, 0.44). Among women, the prevalence increased from <10% in those born before 1960 to 30% in those born after 1980, and smoking was associated with exposure to dust versus not exposed to dust (p value, 0.006), but did not vary appreciably across workers in different cumulative dust exposure categories (p trend, 0.29).

Conclusions: Our study suggests that cross-sectional surveys may be a useful tool for understanding the potential health impact from smoking in occupational cohorts, including possible confounding by smoking. This survey showed that adjustment at the age group level among women is needed to reduce residual confounding and account for smoking patterns, which have changed substantially over time.
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http://dx.doi.org/10.1136/oemed-2019-106263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7476310PMC
September 2020

Risk of second primary papillary thyroid cancer among adult cancer survivors in the United States, 2000-2015.

Cancer Epidemiol 2020 02 26;64:101664. Epub 2019 Dec 26.

Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Institutes of Health, National Cancer Institute, 9609 Medical Center Drive, MSC 9778 Bethesda, MD, 20892-9778, United States.

Background: While radiotherapy is a major risk factor for thyroid cancer after childhood cancer, factors contributing to increased thyroid cancer risk after adulthood cancer remain unclear.

Methods: We evaluated second primary papillary thyroid cancer (PTC) risk among 3,175,216 ≥ 1-year adult survivors of non-thyroid malignancies from US population-based cancer registries (2000-2015), using standardized incidence ratios (SIRs). Because heightened surveillance may increase detection of indolent thyroid tumors and earlier detection of advanced tumors, we examined SIRs by PTC stage and time since first cancer (latency).

Results: SIRs for second primary PTC (N = 4333) were statistically-significantly 1.2-3.5-fold elevated overall and after 23/27 first cancer types evaluated, with generally similar risks for localized and regional/distant PTC. SIRs for regional/distant PTC (N = 1501) were highest after pancreatic (SIR = 3.7; 95% confidence interval [CI] = 1.9-6.5) and soft tissue (SIR = 4.2; 95%CI = 2.8-6.2) cancers, followed by melanoma, chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), diffuse large B-cell lymphoma, and larynx, kidney, and brain/central nervous system (SIRs = 2.0-2.9) cancers. SIRs typically decreased with increasing latency but remained statistically-significantly elevated for regional/distant-PTC ≥5 years after diagnosis of cancers of the rectum, pancreas, lung/bronchus, soft tissue, female breast, uterine corpus, prostate, and kidney, and after melanoma, Hodgkin lymphoma, CLL/SLL, and follicular lymphoma. Neither total nor regional/distant PTC were clearly associated with initial course of radiotherapy or chemotherapy.

Conclusions: PTC risk was elevated after a range of first primary adult cancers but was not clearly related to treatment. Although surveillance may contribute to elevated short-term risks of PTC, longer-term elevations in regional/distant PTC may be attributable to shared risk factors.
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http://dx.doi.org/10.1016/j.canep.2019.101664DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7096211PMC
February 2020

Comparison of Radiation Dose Reconstruction Methods to Investigate Late Adverse Effects of Radiotherapy for Childhood Cancer: A Report from the Childhood Cancer Survivor Study.

Radiat Res 2020 02 3;193(2):95-106. Epub 2019 Dec 3.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.

Quantification of radiation dose to normal tissue during radiotherapy is critical for assessing risk for radiotherapy-related late effects, including subsequent neoplasms (SNs). Case-control studies of SNs typically reconstruct absorbed radiation dose to the specific SN location using individual treatment parameters. A simplified method estimates the maximum prescribed target dose to the body region in which the SN arises. We compared doses and risk estimates from these methods using data from case-control studies of subsequent brain tumors (64 cases, 244 controls) and breast cancer (94 cases, 358 controls) nested within the Childhood Cancer Survivor Study (≥5-year survivors of childhood cancer diagnosed 1970-1986). The weighted kappa statistic [95% confidence interval (CI)] evaluating agreement between categorical (>0-9.9/10-19.9/20-29.9/≥30 Gy) body-region and tumor location-specific doses was 0.95 (0.91-0.98) for brain and 0.76 (0.69-0.82) for breast. The body-region and location-specific doses were assigned to the same dose category for a smaller proportion of patients treated with fields delivering a heterogeneous dose across the tissue of interest (e.g., partial brain field = 57.1%; mantle field = 61.3%) than patients treated with fields delivering a more homogeneous dose (e.g., whole brain field = 100%). Excess odds ratios per Gy (95% CI) from conditional logistic regression were 1.25 (0.33-6.33) and 1.20 (0.31-6.14) for brain tumors and 0.21 (0.05-0.77) and 0.10 (0.02-0.44) for breast cancer, using location-specific and body-region doses, respectively. We observed that body-region doses can approximate location-specific doses when the tissue of interest is clearly in the radiation field or outside the treated body region. Agreement is lower when there is greater ambiguity of SN location relative to the treatment field.
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http://dx.doi.org/10.1667/RR15308.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7063664PMC
February 2020

Bone and Soft-Tissue Sarcoma Risk in Long-Term Survivors of Hereditary Retinoblastoma Treated With Radiation.

J Clin Oncol 2019 12 17;37(35):3436-3445. Epub 2019 Oct 17.

National Cancer Institute, Bethesda, MD.

Purpose: Survivors of hereditary retinoblastoma have excellent survival but substantially increased risks of subsequent bone and soft-tissue sarcomas, particularly after radiotherapy. Comprehensive investigation of sarcoma risk patterns would inform clinical surveillance for survivors.

Patients And Methods: In a cohort of 952 irradiated survivors of hereditary retinoblastoma who were originally diagnosed during 1914 to 2006, we quantified sarcoma risk with standardized incidence ratios (SIRs) and cumulative incidence analyses. We conducted analyses separately for bone and soft-tissue sarcomas occurring in the head and neck (in/near the radiotherapy field) versus body and extremities (out of field).

Results: Of 105 bone and 124 soft-tissue sarcomas, more than one half occurred in the head and neck (bone, 53.3%; soft tissue, 51.6%), one quarter in the body and extremities (bone, 29.5%; soft tissue, 25.0%), and approximately one fifth in unknown/unspecified locations (bone, 17.1%; soft tissue, 23.4%). We noted substantially higher risks compared with the general population for head and neck versus body and extremity tumors for both bone (SIR, 2,213; 95% CI, 1,671 to 2,873 SIR, 169; 95% CI, 115 to 239) and soft-tissue sarcomas (SIR, 542; 95% CI, 418 to 692 SIR, 45.7; 95% CI, 31.1 to 64.9). Head and neck bone and soft-tissue sarcomas were diagnosed beginning in early childhood and continued well into adulthood, reaching a 60-year cumulative incidence of 6.8% (95% CI, 5.0% to 8.7%) and 9.3% (95% CI, 7.0% to 11.7%), respectively. In contrast, body and extremity bone sarcoma incidence flattened after adolescence (3.5%; 95% CI, 2.3% to 4.8%), whereas body and extremity soft-tissue sarcoma incidence was rare until age 30, when incidence rose steeply (60-year cumulative incidence, 6.6%; 95% CI, 4.1% to 9.2%), particularly for females (9.4%; 95% CI, 5.1% to 13.8%).

Conclusion: Strikingly elevated bone and soft-tissue sarcoma risks differ by age, location, and sex, highlighting important contributions of both radiotherapy and genetic susceptibility. These data provide guidance for the development of a risk-based screening protocol that focuses on the highest sarcoma risks by age, location, and sex.
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http://dx.doi.org/10.1200/JCO.19.01096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7001778PMC
December 2019

Risk of therapy-related myelodysplastic syndrome/acute myeloid leukemia after childhood cancer: a population-based study.

Leukemia 2019 12 24;33(12):2947-2978. Epub 2019 Jul 24.

Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA.

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http://dx.doi.org/10.1038/s41375-019-0520-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6884663PMC
December 2019

Risk for malignancies of infectious etiology among adult survivors of specific non-Hodgkin lymphoma subtypes.

Blood Adv 2019 07;3(13):1961-1969

Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, US Department of Health and Human Services, Bethesda, MD.

Infectious agents have been identified in the etiology of certain non-Hodgkin lymphoma (NHL) subtypes and solid tumors. The impact of this shared etiology on risk for second cancers in NHL survivors has not been comprehensively studied. We used US population-based cancer registry data to quantify risk of solid malignancies associated with infectious etiology among 127 044 adult 1-year survivors of the 4 most common NHL subtypes diagnosed during 2000 to 2014 (mean follow-up, 4.5-5.2 years). Compared with the general population, elevated risks for liver, stomach, and anal cancers were observed among diffuse large B-cell lymphoma (DLBCL) survivors (standardized incidence ratio [SIR], 1.85; 95% confidence interval [CI], 1.46-2.31; SIR, 1.51; 95% CI, 1.16-1.94; SIR, 3.71; 95% CI, 2.52-5.27, respectively) and marginal zone lymphoma (MZL; SIR, 1.98; 95% CI, 1.34-2.83; SIR, 2.78; 95% CI, 2.02-3.74; SIR, 2.36; 95% CI, 1.02-4.64, respectively) but not follicular lymphoma or chronic lymphocytic leukemia/small lymphocytic lymphoma. Anal cancer risk was particularly elevated among DLBCL survivors with HIV (SIR, 68.34; 95% CI, 37.36-114.66) vs those without (SIR, 2.09; 95% CI, 1.22-3.34). The observed patterns are consistent with shared associations between these cancers and hepatitis C virus, , and HIV, respectively. In contrast, risks for cervical and oropharyngeal/tonsil cancers were not elevated among survivors of any NHL subtype, possibly because of the lack of NHL association with human papillomavirus or population-wide screening practices (for cervical cancer). In summary, patterns of elevated second cancer risk differed by NHL subtype. Our results suggest shared infectious etiology has implications for subsequent cancer risks among DLBCL and MZL survivors, which may help inform surveillance for these survivors.
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http://dx.doi.org/10.1182/bloodadvances.2019030924DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6616262PMC
July 2019

Association of Chemotherapy for Solid Tumors With Development of Therapy-Related Myelodysplastic Syndrome or Acute Myeloid Leukemia in the Modern Era.

JAMA Oncol 2019 03;5(3):318-325

Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland.

Importance: Therapy-related myelodysplastic syndrome or acute myeloid leukemia (tMDS/AML) is a rare, usually fatal complication of chemotherapy, including certain alkylating agents, topoisomerase II inhibitors, and platinum compounds. With the introduction of new chemotherapeutic agents, expanded indications for established agents, and increased neoadjuvant and adjuvant chemotherapy, tMDS/AML risks in the modern age are poorly understood.

Objectives: To quantify tMDS/AML risk after chemotherapy for solid cancer among United States adults since 2000 and correlate tMDS/AML risk patterns with chemotherapy treatment practices.

Design, Setting, And Participants: A population-based cohort study was conducted using cancer registries from the Surveillance, Epidemiology, and End Results (SEER) Program and Medicare claims. Risk analyses included 1619 tMDS/AML cases among 700 612 adults (age, 20-84 years) who were diagnosed with first primary solid cancer during 2000 to 2013 (followed up through 2014), received initial chemotherapy, and survived 1 year or longer, as reported to SEER. Descriptive analyses were conducted of SEER records linked with Medicare claims for chemotherapy in 165 820 older adults (age, 66-84 years) receiving initial chemotherapy for a first primary solid cancer in 2000-2013. Data analysis was conducted from October 2017 to April 2018.

Exposures: Receipt of initial chemotherapy for solid cancer.

Main Outcomes And Measures: Second primary tMDS/AML.

Results: Based on 1619 tMDS/AML cases in the SEER database (mean [SD] age, 64.3 [12.2] years; 1148 [70.9%] female), tMDS/AML risks were statistically significantly elevated after chemotherapy for 22 of 23 solid cancers (all except colon). Relative risks ranged from 1.5 to greater than 10 and excess absolute risks from 1.4 to greater than 15 cases per 10 000 person-years compared with the general population. Overall survival following tMDS/AML diagnosis was poor (1270 of 1619 patients [78.4%] died; median overall survival, 7 months). For patients treated with chemotherapy at the present time, approximately three-quarters of tMDS/AML cases expected to occur within the next 5 years will be attributable to chemotherapy. In the SEER-Medicare database, use of known leukemogenic agents, particularly platinum compounds, in initial chemotherapy increased substantially since 2000, most notably for gastrointestinal tract cancers (esophagus, stomach, colon, and rectum; 10% in 2000-2001 to 81% during 2012-2013).

Conclusions And Relevance: Large-scale, United States population-based data demonstrate excess tMDS/AML risks following chemotherapy for nearly all solid tumor types, consistent with expanded use of known leukemogenic agents in the 21st century. Continued efforts to reduce treatment-related adverse events, particularly for solid cancer patients with favorable prognosis, are needed.
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http://dx.doi.org/10.1001/jamaoncol.2018.5625DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6439835PMC
March 2019

Mutual Risks of Cutaneous Melanoma and Specific Lymphoid Neoplasms: Second Cancer Occurrence and Survival.

J Natl Cancer Inst 2018 11;110(11):1248-1258

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD.

Background: It is unclear whether the established association between cutaneous melanoma (CM) and lymphoid neoplasms (LNs) differs across LN subtypes. This study quantifies risk for developing CM after specific LNs and, conversely, for developing specific LNs after CM, as well as assessing clinical impact.

Methods: We identified a cohort of Caucasian adults (age 20-83 years) initially diagnosed with CM or LN, as reported to 17 US population-based cancer registries, 2000-2014. Standardized incidence ratios (SIRs) quantified second cancer risk. We assessed impact of second cancer development on risk of all-cause mortality using Cox regression.

Results: Among 151 949 one-or-more-year survivors of first primary LN, second primary CM risk was statistically significantly elevated after chronic lymphocytic leukemia/small lymphocytic lymphoma (SIR = 1.96, 95% confidence interval [CI] = 1.74 to 2.21), follicular lymphoma (SIR = 1.32, 95% CI = 1.09 to 1.58), and plasma cell neoplasms (SIR = 1.33, 95% CI = 1.07 to 1.63). Risks for these same subtypes were statistically significantly elevated among 148 336 survivors of first primary CM (SIR = 1.44, 95% CI = 1.25 to 1.66; SIR = 1.47, 95% CI = 1.21 to 1.77; SIR = 1.25, 95% CI = 1.06 to 1.47; respectively). Risk for CM was statistically significantly elevated after diffuse large B-cell lymphoma (SIR = 1.22, 95% CI = 1.02 to 1.45) and Hodgkin lymphoma (SIR = 1.75, 95% CI = 1.33 to 2.26), but the reciprocal relationship was not observed. There were no statistically significant associations between marginal zone lymphoma and CM. Among survivors of most LN subtypes, CM statistically significantly increased risk of death (hazard ratio [HR] range = 1.52, 95% CI = 1.25 to 1.85, to 2.46, 95% CI = 1.45 to 4.16). Among survivors of CM, LN statistically significantly increased risk of death (HR range = 1.75, 95% CI = 1.15 to 2.65, to 6.28, 95% CI = 5.00 to 7.88), with the highest risks observed for the most aggressive LN subtypes.

Conclusions: Heterogeneous associations between CM and specific LN subtypes provide novel insights into the etiology of these malignancies, with the mutual association between CM and certain LN suggesting shared etiology. Development of second primary CM or LN substantially reduces overall survival.
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http://dx.doi.org/10.1093/jnci/djy052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6454551PMC
November 2018

Association of Treatment for Hodgkin Lymphoma With Estrogen Receptor Status of Subsequent Breast Cancers.

JAMA Oncol 2018 Mar;4(3):414-416

Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.

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http://dx.doi.org/10.1001/jamaoncol.2017.4887DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5885823PMC
March 2018

Temporal Trends in Airborne Dust Concentrations at a Large Chrysotile Mine and its Asbestos-enrichment Factories in the Russian Federation During 1951-2001.

Ann Work Expo Health 2017 Aug;61(7):797-808

Institute for Risk Assessment Sciences, Utrecht University, Yalelaan 2, 3584 Utrecht, The Netherlands.

Objectives: Mining and processing of chrysotile, an established carcinogen, has been undertaken in Asbest, Russian Federation since the late 1800s. Dust concentrations were routinely recorded at the open-pit mine and its asbestos-enrichment factories. We examined the temporal trends in these dust concentrations from 1951 to 2001.

Methods: Analyses included 89290 monthly averaged gravimetric dust concentrations in six factories (1951-2001) and 1457 monthly averaged concentrations in the mine (1964-2001). Annual percent changes (APC) in geometric mean dust concentrations were estimated for each factory and the mine separately from linear mixed models of the logarithmic-transformed monthly averaged concentrations.

Results: Dust concentrations declined significantly in the mine [APC: -1.6%; 95% confidence interval (CI): -3.0 to -0.2] and Factories 1-5 but not 6. Overall factory APCs ranged from -30.4% (95% CI: -51.9 to -8.9; Factory 1: 1951-1955) to -0.6% (95% CI: -1.5 to 0.2; Factory 6: 1969-2001). Factory trends varied across decades, with the steepest declines observed before 1960 [APCs: -21.5% (Factory 2) and -17.4% (Factory 3)], more moderate declines in the 1960s and 1970s [APCs from -10% in Factory 2 (1960s) to -0.3% (not statistically significant) in Factory 4 (1970s)], and little change thereafter. Mine dust concentrations increased in the 1960s (APC: +9.7%; 95% CI: 3.6 to 15.9), decreased in the 1990s (APC: -5.8%; 95% CI: -8.1 to -3.5) and were stable in between.

Conclusions: In this analysis of >90000 dust concentrations, factory dust concentrations declined between 1951 and 1979 and then stabilized. In the mine, dust levels increased in the 1960s, declined in the 1990s and were unchanged in the interim.
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http://dx.doi.org/10.1093/annweh/wxx051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6005011PMC
August 2017

Radiotherapy for ductal carcinoma in situ and risk of second non-breast cancers.

Breast Cancer Res Treat 2017 Nov 25;166(1):299-306. Epub 2017 Jul 25.

Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.

Purpose: Radiotherapy for ductal carcinoma (DCIS) is increasing, but the risks and benefits of the treatment remain uncertain. We aimed to investigate the relationship between radiotherapy for DCIS and risk of second non-breast cancers in a large US cohort.

Methods: We conducted a retrospective cohort study of 52,556 women in 12 U.S. population-based cancer registries diagnosed with first primary DCIS during 1992-2008 at age 25-79 years. We estimated relative risks (RRs), attributable risks (AR), and excess absolute risks (EAR) of second non-breast cancers associated with radiotherapy using Poisson regression adjusted for age at year of diagnosis, grade, hormonal therapy (yes/no or unknown), and time since diagnosis.

Results: Approximately half of the women (46.3%) received radiotherapy. Radiotherapy was associated with an increased risk of all second non-breast cancers combined [RR 1.17, 95% confidence interval (CI) 1.08-1.28] and all in-field, radiation-related second cancers combined (RR 1.37, 95% CI 1.15-1.63), driven by second lung cancers (RR 1.33, 95% CI 1.10-1.60) and non-CLL leukemia (RR 1.71, 95% CI 1.02-2.86). The estimated cumulative excess risk of all second non-breast cancers was 0.8% by 15 years after DCIS diagnosis.

Conclusions: Radiotherapy was associated with an increased risk of second non-breast cancers. The specific excess of cancers at sites likely in/near the radiotherapy field suggests the findings are unlikely due exclusively to confounding, but further research into factors related to receipt of radiotherapy is needed. Our risk estimates can be used to help assess the balance of the risks and benefits of radiotherapy for DCIS and to inform clinical practice.
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http://dx.doi.org/10.1007/s10549-017-4410-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7271498PMC
November 2017

A comparison of parallel dust and fibre measurements of airborne chrysotile asbestos in a large mine and processing factories in the Russian Federation.

Int J Hyg Environ Health 2017 07 13;220(5):857-868. Epub 2017 Apr 13.

Division of Environmental Epidemiology, Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands. Electronic address:

Introduction: Historic dust concentrations are available in a large-scale cohort study of workers in a chrysotile mine and processing factories in Asbest, Russian Federation. Parallel dust (gravimetric) and fibre (phase-contrast optical microscopy) concentrations collected in 1995, 2007 and 2013/14 were used to determine if dust to fibre conversion factors can be estimated.

Materials/subjects And Methods: Daily medians of multiple parallel dust and fibre concentrations by sampling points were used to derive fibre to dust ratios. Applying linear mixed models, we estimated best linear unbiased predictions for the fibre to dust ratios.

Results And Discussion: A total of 620 daily median fibre to dust ratios were derived. In the factories, modelled ratios varied by unit, increasing along the stages of asbestos enrichment as expected. In the mine, ratios were higher in winter compared to summer. Overall, the ratios showed a strong negative dependency on dust concentration.

Conclusions: Our study shows that dust to fibre conversion is possible by unit but extrapolations are needed. The patterns for exposure by dust and fibre will be similar but estimated fibre levels will show less contrast due to the conversion factor being smaller at higher dust concentrations.
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http://dx.doi.org/10.1016/j.ijheh.2017.04.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6464639PMC
July 2017

Hematologic malignancies in South Africa 2000-2006: analysis of data reported to the National Cancer Registry.

Cancer Med 2016 Apr 15;5(4):728-38. Epub 2016 Jan 15.

Section of Environment and Radiation, International Agency for Research on Cancer (IARC), Lyon, France.

Little is known about the incidence patterns of hematologic malignancies in Sub-Saharan Africa, including South Africa. We estimated incidence rates of pathology-confirmed adult cases of leukemia, myeloma and related diseases (myeloma), Hodgkin lymphoma (HL), and non-Hodgkin lymphoma (NHL) reported to the National Cancer Registry of South Africa (NCR) between 2000 and 2006, by age, gender, and population group (Black, White, Coloured, Asian/Indian). Gender-specific age-standardized rates were calculated overall and by population group and incidence rate ratios (IRRs) were estimated using Poisson regression models. Between 2000 and 2006, there were 14662 cases of leukemia, myeloma, HL, and NHL reported to the registry. Incidence rates of reported hematologic malignancies were generally 20-50% higher among males than females. Our analyses suggested marked differences in the rates of reported hematologic malignancies by population group which were most pronounced when comparing the White versus Black population groups (IRRs ranging from 1.6 for myeloma to 3.8 for HL for males and females combined). Challenges related to diagnosis and reporting of cancers may play a role in the patterns observed by population group while the set-up of the NCR (pathology-based) could lead to some degree of under-ascertainment in all groups. This is the first country-wide report of the incidence of hematologic malignancies in South Africa. Despite challenges, it is important to analyze and report available national cancer incidence data to raise awareness of the cancer burden and to characterize patterns by demographic characteristics so as ultimately to improve the provision of cancer-related health care.
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http://dx.doi.org/10.1002/cam4.597DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4831292PMC
April 2016

Meeting report: suggestions for studies on future health risks following the Fukushima accident.

Environ Health 2015 Mar 19;14:26. Epub 2015 Mar 19.

Radiation Medical Science Center, Fukushima Medical University, 1 Hikarigaoka, Fukushima, 960-1295, Japan.

In October 2013, the Radiation Medical Science Center of the Fukushima Medical University and the Section of Environment and Radiation of the International Agency for Research on Cancer held a joint workshop in Fukushima, Japan to discuss opportunities and challenges for long-term studies of the health effects following the March 2011 Fukushima Daiichi Nuclear Power Plant Accident. This report describes four key areas of discussion -- thyroid screening, dosimetry, mental health, and non-radiation risk factors -- and summarizes recommendations resulting from the workshop. Four recommendations given at the workshop were to: 1) build-up a population-based cancer registry for long-term monitoring of the cancer burden in the prefecture; 2) enable future linkage of data from the various independent activities, particularly those related to dose reconstruction and health status ascertainment; 3) establish long-term observational studies with repeated measurements of lifestyle and behavioural factors to disentangle radiation and non-radiation factors; and 4) implement primary prevention strategies targeted for populations affected by natural disasters, including measures to better understand and address health risk concerns in the affected population. The workshop concluded that coordinated data collection between researchers from different institutes and disciplines can both reduce the burden on the population and facilitate efforts to examine the inter-relationships between the many factors at play.
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http://dx.doi.org/10.1186/s12940-015-0013-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4369075PMC
March 2015

Childhood cancer incidence patterns by race, sex and age for 2000-2006: a report from the South African National Cancer Registry.

Int J Cancer 2015 Jun 21;136(11):2628-39. Epub 2014 Nov 21.

Section of Environment and Radiation, International Agency for Research on Cancer (IARC), 150 Cours Albert Thomas, 69372, Lyon, France.

Higher childhood cancer incidence rates are generally reported for high income countries although high quality information on descriptive patterns of childhood cancer incidence for low or middle income countries is limited, particularly in Sub-Saharan Africa. There is a need to quantify global differences by cancer types, and to investigate whether they reflect true incidence differences or can be attributed to under-diagnosis or under-reporting. For the first time, we describe childhood cancer data reported to the pathology report-based National Cancer Registry of South Africa in 2000-2006 and compare our results to incidence data from Germany, a high income country. The overall age-standardized incidence rate (ASR) for South Africa in 2000-2006 was 45.7 per million children. We observed substantial differences by cancer types within South Africa by racial group; ASRs tended to be 3-4-fold higher in South African Whites compared to Blacks. ASRs among both Black and White South Africans were generally lower than those from Germany with the greatest differences observed between the Black population in South Africa and Germany, although there was marked variation between cancer types. Age-specific rates were particularly low comparing South African Whites and Blacks with German infants. Overall, patterns across South African population groups and in comparison to Germans were similar for boys and girls. Genetic and environmental reasons may probably explain rather a small proportion of the observed differences. More research is needed to understand the extent to which under-ascertainment and under-diagnosis of childhood cancers drives differences in observed rates.
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http://dx.doi.org/10.1002/ijc.29308DOI Listing
June 2015

Regional variations in German mesothelioma mortality rates: 2000–2010.

Cancer Causes Control 2014 May;25(5):615-24

Purpose: Germany has one of the highest age-adjusted mesothelioma mortality rates worldwide. As mesothelioma occurs ≥ 30 years after asbestos exposure, contemporary rates likely reflect exposures in the 1960-1970s. During this period, political division between West and East Germany led to differences regarding the import and consumption of asbestos. It is unclear whether mesothelioma rates also differ between these formerly separate countries which are now served by similar health and mortality reporting systems, thereby facilitating regional comparisons.

Methods: We examined regional, temporal, and sex variations in mesothelioma mortality rates in Germany in 2000-2010, collapsing the federal states into West Germany, East Germany, and Berlin. We calculated truncated (≥ 40 years) age-standardized mesothelioma mortality rates (ASRs(40+)) per 100,000 person-years, estimated sex-stratified mortality rate ratios (MRRs) (95 % confidence intervals (CIs)), adjusted for age and calendar year from Poisson models, and fitted age-period-cohort models.

Results: There were 12,854 mesothelioma deaths at ages ≥ 40 years in Germany during 2000-2010. ASRs(40+) were higher in West (males 4.4; females 0.8) than East (males 1.7; females 0.6) Germany. MRRs for West versus East Germany were 2.68 (95 % CI 2.48-2.88) among males and 1.42 (95 % CI 1.27-1.59) among females. In both regions, mortality rates increased for birth cohorts until the mid 1940s and subsequently declined. The country's peak mesothelioma burden is predicted to occur by 2020.

Conclusions: Geographical differences in mesothelioma mortality rates are consistent with heterogeneous historical asbestos exposures. Differences may exist for other asbestos-related cancers and should be investigated in analytic studies with individual asbestos exposure information.
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http://dx.doi.org/10.1007/s10552-014-0368-4DOI Listing
May 2014

Benign breast and gynecologic conditions, reproductive and hormonal factors, and risk of thyroid cancer.

Cancer Prev Res (Phila) 2014 Apr 21;7(4):418-25. Epub 2014 Jan 21.

National Cancer Institute, National Institutes of Health, 9609 Medical Center Drive, Bethesda, MD 20892.

The higher incidence of thyroid cancer in women compared with men suggests an influence of sex steroid hormones in the etiology of this malignancy. We investigated a comprehensive set of potential indicators of lifetime sex steroid hormone exposure in relation to thyroid cancer risk. Using data from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, which enrolled 70,047 women, 50 to 78 years old, we prospectively examined associations of self-reported history of benign breast and gynecologic conditions, reproductive factors, and exogenous sex hormone use with thyroid cancer risk. Multivariable-adjusted HRs and 95% confidence intervals (CI) were calculated in models using age as the time metric. During follow-up (median, 11 years), 127 women were diagnosed with first primary thyroid cancer. Older age at natural menopause (≥55 vs. <50 years; HR, 2.24; 95% CI, 1.20-4.18), greater estimated lifetime number of ovulatory cycles (≥490 vs. <415 cycles; HR, 2.40; 95% CI, 1.33-4.30), greater number of live births (≥5 vs. 1-2; HR, 1.72; 95% CI, 1.05-2.82), and history of uterine fibroids (HR, 1.72; 95% CI, 1.18-2.50) were associated with an increased risk of thyroid cancer. Earlier age at menarche, greater number of reproductive years, history of a tubal ligation, and history of ovarian cysts were nonsignificantly associated with increased thyroid cancer risk. No associations were observed for oral contraceptive use, menopausal hormone therapy, or history of benign breast disease or endometriosis. In general, we found that factors reflecting a greater length of exposure to endogenous hormones, particularly during the reproductive years, were associated with risk of postmenopausal thyroid cancer.
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http://dx.doi.org/10.1158/1940-6207.CAPR-13-0367DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3976437PMC
April 2014

Reproductive factors and kidney cancer risk in 2 US cohort studies, 1993-2010.

Am J Epidemiol 2013 Jun 26;177(12):1368-77. Epub 2013 Apr 26.

Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.

Clinical and experimental findings suggest that female hormonal and reproductive factors could influence kidney cancer development. To evaluate this association, we conducted analyses in 2 large prospective cohorts (the National Institutes of Health-AARP Diet and Health Study (NIH-AARP), 1995-2006, and the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO), 1993-2010). Cohort-specific and aggregated hazard ratios and 95% confidence intervals relating reproductive factors and kidney cancer risk were computed by Cox regression. The analysis included 792 incident kidney cancer cases among 283,952 postmenopausal women. Women who had undergone a hysterectomy were at a significantly elevated kidney cancer risk in both NIH-AARP (hazard ratio = 1.28, 95% confidence interval: 1.09, 1.50) and PLCO (hazard ratio = 1.41, 95% confidence interval: 1.06, 1.88). Similar results were observed for both cohorts after analyses were restricted to women who had undergone a hysterectomy with or without an oophorectomy. For the NIH-AARP cohort, an inverse association was observed with increasing age at menarche (P for trend = 0.02) and increasing years of oral contraceptive use (P for trend = 0.02). No clear evidence of an association with parity or other reproductive factors was found. Our results suggest that hysterectomy is associated with increased risk of kidney cancer. The observed associations with age at menarche and oral contraceptive use warrant further investigation.
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http://dx.doi.org/10.1093/aje/kws406DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3676151PMC
June 2013

Declining second primary ovarian cancer after first primary breast cancer.

J Clin Oncol 2013 Feb 2;31(6):738-43. Epub 2013 Jan 2.

Department of Health and Human Services, National Institutes of Health, National Cancer Institute, Bethesda, MD, USA.

Purpose: Although ovarian cancer incidence rates have declined in the United States, less is known of ovarian cancer trends among survivors of breast cancer. Therefore, we examined second primary ovarian cancers after first primary breast cancer.

Methods: Data were obtained from the Surveillance, Epidemiology, and End Results program (1973 to 2008). Standardized incidence ratios (SIRs) were calculated as the observed numbers of ovarian cancers among survivors of breast cancer compared with the expected numbers in the general population. Absolute rates were measured as the incidence rates for second primary ovarian cancer by year of diagnosis of the first primary breast cancer adjusted for age of breast cancer diagnosis and years since diagnosis.

Results: SIRs for second primary ovarian cancer were elevated over the entire study period (SIR, 1.24; 95% CI, 1.2 to 1.3), whereas the absolute rates declined with an estimated annual percentage change near 1% (-1.34% to -0.09% per year). Secular trends for second ovarian cancers were similar after estrogen receptor (ER) -positive and ER-negative breast cancers, whereas the age-specific patterns varied significantly by ER expression (P for interaction < .001). The largest SIR was among women age less than 50 years with ER-negative breast cancer (SIR, 4.35; 95% CI, 3.5 to 5.4).

Conclusion: Persistently elevated SIRs along with decreasing absolute rates over the entire study period suggest that ovarian cancers in both the general population and survivors of breast cancer are declining in parallel, possibly because of common risk factor exposures. Analytic studies are needed to further assess the parallel overall trends and the age-specific interaction by ER expression.
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http://dx.doi.org/10.1200/JCO.2012.43.2757DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3574269PMC
February 2013

An aggregated analysis of hormonal factors and endometrial cancer risk by parity.

Cancer 2013 Apr 20;119(7):1393-401. Epub 2012 Dec 20.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Background: Nulliparity is associated with an increased risk of endometrial cancer. It is less clear whether nulliparity modifies the association between other established hormone-related risk factors. The proportion of nulliparous women has increased since the mid-1970s, but most individual studies to date have been too small to test the hypothesis that endometrial cancer risk factors may be associated more strongly with risk among nulliparous women compared with parous women.

Methods: Data were aggregated on 26,936 postmenopausal, Caucasian, nulliparous women (360 endometrial cancers) and 146,583 postmenopausal, Caucasian, parous women (1378 endometrial cancers) from 4 US prospective studies (1979-2006). Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated in stratified analyses.

Results: The risk of endometrial cancer was higher among nulliparous women than among parous women, as expected (nulliparous vs parous: HR, 1.42; 95% CI, 1.26-1.60). Stratified associations between endometrial cancer and hormone-related risk factors did not differ between nulliparous versus parous women: For both groups, oral contraceptives and earlier menopause were associated with reduced risk. The highest HRs were for obesity: A body mass index ≥30 kg/m(2) (vs <25 kg/m(2) ) increased the risk of endometrial cancer 3-fold among nulliparous women (HR, 3.04; 95% CI, 2.34-3.94) and parous women (HR, 2.88; 95% CI, 2.52-3.29).

Conclusions: The results from this large, pooled analysis of data from 4 large prospective studies suggested that nulliparity does not modify the risks of endometrial cancer associated with established hormone-related risk factors.
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http://dx.doi.org/10.1002/cncr.27909DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3744666PMC
April 2013

Sarcomas in hereditary retinoblastoma.

Clin Sarcoma Res 2012 Oct 4;2(1):15. Epub 2012 Oct 4.

Epidemiology and Biostatistics Program Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 6120 Executive Boulevard, Rockville, MD 20852, USA.

Children diagnosed with the hereditary form of retinoblastoma (Rb), a rare eye cancer caused by a germline mutation in the RB1 tumor suppressor gene, have excellent survival, but face an increased risk of bone and soft tissue sarcomas. This predisposition to sarcomas has been attributed to genetic susceptibility due to inactivation of the RB1 gene as well as past radiotherapy for Rb. The majority of bone and soft tissue sarcomas among hereditary Rb survivors occur in the head, within the radiation field, but they also occur outside the radiation field. Sarcomas account for almost half of the second primary cancers in hereditary Rb survivors, but they are very rare following non-hereditary Rb. Sarcomas among hereditary Rb survivors arise at ages similar to the pattern of occurrence in the general population. There has been a trend over the past two decades to replace radiotherapy with chemotherapy and other focal therapies (laser or cryosurgery), and most recently, chemosurgery in order to reduce the incidence of sarcomas and other second cancers in Rb survivors. Given the excellent survival of most Rb patients treated in the past, it is important for survivors, their families and health care providers to be aware of the heightened risk for sarcomas in hereditary patients.
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http://dx.doi.org/10.1186/2045-3329-2-15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3499233PMC
October 2012