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Scientific Highlights

July 2011 - Linkage Newsletter


AIDS-Related Cancer

Cancer Among the HIV-infected

Purpose: As a result of effective anti-retroviral therapy, more HIV-infected people are surviving long enough to be at risk for non–AIDS-defining cancers that typically occur at older ages. This study estimated the annual number of cancers in the HIV-infected population, both with and without AIDS, in the United States. Methods: The authors obtained estimated counts of individual AIDS-defining and non–AIDS-defining cancers in the AIDS and HIV-infected populations through the HIV/AIDS Cancer Match Study, which links data from the U.S. population-based HIV and cancer registries. Results and conclusions: In the AIDS population, the number of AIDS-defining cancers declined sharply between 1991 and 1997, with more gradual decreases in subsequent years (see Figure 1). Notwithstanding these decreases, KS and NHL remain the most common malignancies in the U.S. AIDS population. The number of non–AIDS-defining cancers increased steadily from 1991 to 2005 and, since 2003, has exceeded the annual number of AIDS-defining cancers. The steep increase in non–AIDS-defining cancers among the HIV-infected population has largely been driven by the growth and aging of that population. (Shiels MS, Pfeiffer RM, Gail MH, et al. Cancer burden in the HIV-infected population in the United States. J Natl Cancer Inst 2011;103:753–762)

Impact of HIV on Cancer in the United States

Purpose: To quantify the impact of HIV on the total number of U.S. cases of certain AIDS-defining cancers (KS, diffuse large B-cell lymphoma [DLBCL], Burkitt lymphoma [BL], central nervous system [CNS] lymphoma, and cervical cancer), the authors determined the proportions of these cancers that occurred among people with AIDS from 1980 to 2007 as compared to the total number of cases that occurred in the United States. Methods: The authors obtained estimated counts from the HIV/AIDS Cancer Match Study (1980–2007) and derived cancer rates for people with and without AIDS. To estimate national counts, they applied the rates to national AIDS surveillance and U.S. census data. Results and conclusions: In the United States, HIV contributed substantially to the total numbers of the cancers in question; 82% of KS cases, 6% of DLBCL, 20% of BL, 27% of CNS lymphomas, and 0.4% of cervical cancer cases occurred among people with AIDS from 1980 to 2007. The proportion of these cancers with AIDS was highest in the mid-1990s and then declined, likely due to the introduction of highly active antiretroviral therapy in 1996. A higher proportion of cases with AIDS occurred among people less than 60 years old than among people older than 60. (Shiels MS, Pfeiffer RM, Hall HI, et al. Proportions of Kaposi sarcoma, selected non-Hodgkin lymphomas, and cervical cancer in the United States occurring in persons with AIDS, 1980-2007. JAMA 2011;305:1450–1459)

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Bladder Cancer

GSTM1 and NAT2 Genes and Smoking

Purpose: To investigate associations of the GSTM1, GSTT1, and NAT2 genotypes, as well as smoking, with bladder cancer risk. Methods: In the New England Bladder Cancer Study, the authors collected mouthwash samples for DNA extraction from 1,088 cases and 1,282 controls for genotype analysis of GSTM1, GSTT1, and NAT2 polymorphisms. They also updated a meta-analysis of NAT2 variants, smoking, and bladder cancer risk, based on 7,961 cases and 13,819 controls. Results and conclusions: ORs for bladder cancer among subjects with one or two inactive GSTM1 alleles were 1.26 and 1.54, respectively, compared to those with two active copies. Inactive GSTT1 alleles were not associated with risk, nor was NAT2 slow acetylation status among never, former, or current smokers. However, among slow acetylators who ever smoked at least 40 cigarettes/day, risk was elevated among ever (OR = 1.82) and current heavy smokers (OR = 3.16). The effect of the GSTM1-null genotype was not greater among smokers, regardless of intensity. Meta-analysis of the NAT2 associations with bladder cancer showed a highly significant relationship. (Moore LE, Baris DR, Figueroa JD, et al. GSTM1 null and NAT2 slow acetylation genotypes, smoking intensity and bladder cancer risk: Results from the New England Bladder Cancer Study and NAT2 meta-analysis. Carcinogenesis 2011;32:182–189)

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Breast Cancer

Breast Cancer Risk in Asian and Pacific Islander American Women

Purpose: To develop a model for projecting absolute invasive breast cancer risk in Asian and Pacific Islander American (APA) women and to compare its projections to those from NCI's Breast Cancer Risk Assessment Tool (BCRAT). Methods: The authors used data from 589 women with breast cancer and 952 women without breast cancer in the Asian American Breast Cancer Study (AABCS) to compute relative and attributable risks. Absolute risks were obtained by combining this information with ethnicity-specific data from SEER and with U.S. ethnicity-specific mortality data to create the AABCS model. Data from the Women's Health Initiative were used to check the calibration and accuracy of the new model. Results and conclusions: Relative and attributable risks for APA women were comparable to those in BCRAT; however, the AABCS model usually estimated lower risk projections than BCRAT in Chinese and Filipino women but not in Hawaiian women. The AABCS model was calibrated to ethnicity-specific incidence rates from the SEER program for projecting absolute invasive breast cancer risk and is preferable to BCRAT for counseling APA women. (Matsuno RK, Costantino JP, Ziegler RG, et al. Projecting individualized absolute invasive breast cancer risk in Asian and Pacific Islander American women. J Natl Cancer Inst 2011;103:951–961)

Breast Cancer Risk Factors and Tumor Subtypes

Purpose: To investigate associations between epidemiological risk factors (age at menarche, parity, age at first full-term birth, family history of breast cancer in first-degree relatives, and current BMI) and tumor subtypes (hormone receptor–positive, hormone receptor–negative, and triple-negative or core basal phenotype [CBP] tumors). Methods: Using pooled tumor marker and epidemiological risk factor data from 35,568 invasive breast cancer patients from 34 studies participating in the Breast Cancer Association Consortium, the authors performed case-case and case-control analyses to estimate associations between epidemiological factors and the risk of developing specific tumor subtypes. Results and conclusions: Reproductive factors and BMI are most clearly associated with hormone receptor–positive tumors and suggest that triple-negative or CBP tumors may have distinct etiology. (Yang XR, Chang-Claude J, Goode EL, et al. Associations of breast cancer risk factors with tumor subtypes: A pooled analysis from the Breast Cancer Association Consortium studies. J Natl Cancer Inst 2011;103:250–263)

Diet, Physical Activity, and Prognosis

Purpose: To investigate post-diagnosis diet quality, recreational physical activity, and prognosis among women with breast cancer. Methods: The authors evaluated data on 670 women from the Health, Eating, Activity, and Lifestyle Study, a multiethnic prospective cohort study of women with first primary breast cancer. Women completed assessments approximately 6 and 30 months after diagnosis and were followed for 6 years. Results and conclusions: Women consuming better quality diets, as defined by higher Healthy Eating Index-2005 scores, had a 60% reduced risk of death from any cause (HRQ4:Q1 = 0.40, CI = 0.17–0.94) and an 88% reduced risk of death from breast cancer (HRQ4:Q1 = 0.12, CI = 0.02–0.99). Compared with inactive survivors consuming poor-quality diets, survivors engaging in any recreational physical activity and consuming better quality diets had an 89% reduced risk of death from any cause (HR = 0.11, CI = 0.04–0.36) and a 91% reduced risk of death from breast cancer (HR = 0.09, CI = 0.01–0.89). Associations observed were independent of obesity status. (George SM, Irwin ML, Smith AW, et al. Postdiagnosis diet quality, the combination of diet quality and recreational physical activity, and prognosis after early-stage breast cancer. Cancer Causes Control 2011;22:589–598)

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Childhood Cancer

Early Life Radiation and Ultrasounds

Purpose: To examine childhood cancer risks associated with exposure to diagnostic radiation and ultrasound scans in utero and in early infancy (ages 0–100 days). Methods: The authors used data from the United Kingdom Childhood Cancer Study, including 2,690 childhood cancer cases and 4,858 age-, sex-, and region-matched controls, to estimate risks of all childhood cancers, leukemia, lymphoma, and central nervous system tumors. Results and conclusions: There was no evidence of increased risk of childhood cancer with in utero exposure to ultrasound scans. After in utero exposure to x-rays, non-significant increases in risk for all cancers (OR = 1.14) and leukemia (OR = 1.36) were observed. Exposure to diagnostic x-rays in early infancy was associated with small, nonsignificant excess risks for all cancers and leukemia, and significant increased risk of lymphoma (OR = 5.14), based on small numbers. The results suggest the need for cautious use of diagnostic radiation imaging procedures to the abdomen/pelvis of the mother during pregnancy and in children at very young ages. (Rajaraman P, Simpson J, Neta G, et al. Early life exposure to diagnostic radiation and ultrasound scans and risk of childhood cancer: Case-control study. BMJ 2011;342:d472)

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Esophageal Cancer

Esophageal Cancer in Young People

Purpose: The authors conducted a retrospective study to better understand the unusual percentage of esophageal cancer (EC) cases in subjects 30 years of age or younger in Western Kenya. Methods: The authors abstracted data from the records of 109 young patients diagnosed with EC at Tenwek Hospital in Bomet District, Kenya, from January 1996 through June 2009 and successfully located and interviewed 60 patients or family members to obtain data on clinical course. Results and conclusions: The median survival time was 6.14 months, and the most common tumor histology was esophageal squamous cell carcinoma (98%). The male-to-female ratio was 1.4 to 1, and family history was prominent, with 79% reporting a family history of cancer and 43% reporting a family history of EC. (Dawsey SP, Tonui S, Parker RK, et al. Esophageal cancer in young people: A case series of 109 cases and review of the literature. PLoS Genet 2010;5:e14080)

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Genes and Habitual Caffeine Consumption

Purpose: To search for common genetic variants associated with habitual caffeine consumption, which has been associated with manifold physiologic effects and both detrimental and beneficial health outcomes. Methods: The authors performed a meta-analysis of five U.S. genome-wide association studies comprising 47,341 individuals of European descent. Caffeine intake was assessed using semi-quantitative food-frequency questionnaires. Results and conclusions: Two loci reached genome-wide significance with no evidence for significant between-study heterogeneity. The strongest associated single nucleotide polymorphism (SNP) (rs4410790) is located at 7p21, upstream of AHR (aryl hydrocarbon receptor). The SNP with the second strongest association (rs2470893) mapped to 15q24, between CYP1A1 and CYP1A2. In addition, analyses of 21 candidate genes identified significant gene-based associations between CYP2C9 and ADORA2A and caffeine intake, in addition to CYP1A2 and AHR. Both the AHR and CYP1A2 genes are biologically plausible candidates because CYP1A2 metabolizes caffeine and AHR regulates CYP1A2. (Cornelis MC, Monda KL, Yu K, et al. Genome-wide meta-analysis identifies regions on 7p21 [AHR] and 15q24 [CYP1A2] as determinants of habitual caffeine consumption. PLoS Genet 2011;7:e1002033)

Telomere Genes in Familial Cancer

Purpose: The shelterin complex of genes consists of six proteins (ACD, POT1, TERF1, TERF2, TERF2IP, and TINF2) that form telomeres. Mutations in TINF2 are present in 11%–25% of patients with dyskeratosis congenita (DC), an inherited bone marrow–failure syndrome that puts patients at very high risk of cancer. The authors' objective was to determine whether mutations in five other genes in the shelterin complex are a common cause of DC. Methods: The authors evaluated nine classic DC patients and seven patients classified as "DC-like" based on telomere length and other clinical features. None had mutations in any of the known DC genes. The authors conducted sequence analysis of the promoters, exons, and intron-exon boundaries of ACD, POT1, TERF1, TERF2, and TERF2IP. Results and conclusions: Two variants were present in one patient and a healthy parent but absent in 364 controls. Three other variants were rare (< 1%) but present in both patients and controls. These data suggest that except for TINF2, mutations in shelterin genes are not a common cause of DC. (Savage SA, Giri N, Jessop L, et al. Sequence analysis of the shelterin telomere protection complex genes in dyskeratosis congenita. J Med Genet 2011;48:285–288)

Xeroderma Pigmentosum

Purpose: To determine the frequency of cancer, neurologic degeneration, and mortality in xeroderma pigmentosum (XP) patients with defective DNA repair in a 39-year natural history study. Methods: All 106 XP patients admitted to NIH from 1971 to 2009 were evaluated from clinical records and follow-up. Results and conclusions: The authors observed a 10,000-fold elevation in non-melanoma skin cancer and a more than 2,000-fold increase in melanoma in XP patients under age 20 compared with the U.S. population. The median age at diagnosis of first non-melanoma skin cancer at 9 years (n = 64) was significantly younger than the median age at diagnosis of first melanoma at 22 years (n = 38), suggesting different mechanisms. XP patients with pronounced burning on minimal sun exposure were less likely to develop skin cancer than others, possibly related to extreme sun protection from an early age. Progressive neurologic degeneration was present in 24% (n = 25) with 16 in complementation group XP-D. The most common causes of death were skin cancer (34%), neurologic degeneration (31%), and internal cancer (17%). The median age at death in XP patients with neurodegeneration (29 years) was younger than that in those without neurodegeneration (37 years). The study suggests a major role for DNA repair genes in the etiology of skin cancer and neurologic degeneration. (Bradford PT, Goldstein AM, Tamura D, et al. Cancer and neurologic degeneration in xeroderma pigmentosum: Long term follow-up characterizes the role of DNA repair. J Med Genet 2011;48:168–176)

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Lung Cancer

Coal and Wood Use in the Home

Purpose: To evaluate the association between in-home solid-fuel use, particularly wood, and lung cancer risk. Methods: Using questionnaire data from seven studies in the International Lung Cancer Consortium (5,105 cases and 6,535 controls), the researchers classified subjects as predominant solid-fuel users (e.g., coal, wood) or nonsolid-fuel users (e.g., oil, gas, electricity). Results and conclusions: Compared with non-solidfuel users, predominant coal users (OR = 1.64), particularly coal users in Asia (OR = 4.93), and predominant wood users in North American and European countries (OR = 1.21) experienced higher risk of lung cancer. The results were similar in never-smoking women and other subgroups. Results are consistent with previous observations relating in-home coal use to lung cancer risk and support the hypothesis of a carcinogenic potential of in-home wood use. (Hosgood HD III, Boffetta P, Greenland S, et al. In-home coal and wood use and lung cancer risk: A pooled analysis of the International Lung Cancer Consortium. Environ Health Perspect 2010;118:1743–1747)

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Lymphoproliferative Disorder After Kidney Transplant

Purpose: To examine differences in risk factors between early onset (i.e., within two years of transplantation) post-transplant lymphoproliferative disorder (PTLD) and late onset (i.e., more than two years after transplantation) PTLD in kidney transplant recipients. Methods: The authors conducted a retrospective cohort study using data from the U.S. Scientific Registry of Transplant Recipients. The study included 156,740 kidney transplant recipients, among whom 762 cases of PTLD were diagnosed during follow-up. Results and conclusions: There was a "U-shaped" pattern of incidence with time since transplantation, with high PTLD incidence shortly after transplantation, decreasing until two to four years after transplantation, and rising thereafter (see Figure 2). Risk factors for early-onset PTLD included young age at transplantation and Epstein-Barr virus and cytomegalovirus seronegativity. By comparison, independent risk factors for late-onset PTLD included older age at transplantation and non-Hispanic white race or ethnicity. Steroid maintenance therapy significantly decreased the risk of late-onset PTLD. The bimodal timing and differences in pathology and risk factors suggest that early- and late-onset PTLD are either distinct diseases or a mixture of subtypes with different etiologies. (Quinlan SC, Pfeiffer RM, Morton LM, et al. Risk factors for early-onset and late-onset post-transplant lymphoproliferative disorder in kidney recipients in the United States. Am J Hematol 2011;86:206–209)

Trichloroethylene Exposure

Purpose: To investigate the association between NHL and occupational exposure to trichloroethylene (TCE), a chlorinated solvent used for vapor degreasing of metal parts. Methods: A total of 1,189 cases and 982 controls provided information on their occupational histories and, for selected occupations, on possible workplace exposure to TCE using job-specific interview modules. An industrial hygienist assessed potential TCE exposure based on this information and a review of the TCE industrial hygiene literature. Results and conclusions: NHL was associated with the highest tertiles of estimated average weekly TCE exposure (23 exposed cases; OR = 2.5) and cumulative exposure (24 exposed cases; OR = 2.3, CI = 1.0–5.0) (p for trend = 0.02 and 0.08, respectively). No consistent dose-response relationships across the exposure levels were observed. Overall, neither duration nor intensity of exposure was associated with NHL risk, but the lowest tertile of exposure duration compared with no exposure was related to risk (OR = 2.1, CI = 1.0–4.7). Findings are consistent with an association between high levels of TCE exposure and NHL risk. (Purdue MP, Bakke B, Stewart P, et al. A case-control study of occupational exposure to trichloroethylene and non-Hodgkin lymphoma. Environ Health Perspect 2011;119:232–238)

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Multiple Myeloma

Obesity and Myeloma Precursor Risk

Purpose: To assess the role of obesity and race in relation to monoclonal gammopathy of undetermined significance (MGUS), a precursor of multiple myeloma, which has been related to obesity and to higher rates in the black population. Methods: The investigators screened 1,000 black and 996 white women aged 40–79 years who were of similar socioeconomic status for MGUS. Results and conclusions: A total of 39 (3.9%) blacks and 21 (2.1%) whites had MGUS. Obesity (OR = 1.8), black race (OR = 1.8), and increasing age (older than 55 years vs. younger than 43 years; OR = 2.5) were independently associated with an excess risk of MGUS. Findings support the hypothesis that obesity is etiologically linked to myelomagenesis. The excess of MGUS among blacks compared with whites of similar socioeconomic status supports a role for susceptibility genes in MGUS. (Landgren O, Rajkumar SV, Pfeiffer RM, et al. Obesity is associated with an increased risk of monoclonal gammopathy of undetermined significance among black and white women. Blood 2010;116:1056–1059)

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Renal Cell Carcinoma

Genome-wide Association Study

Purpose: To search for common genetic variants associated with renal cell carcinoma (RCC). Methods: The authors conducted a two-stage genome-wide association study of RCC in 3,772 affected individuals and 8,505 controls of European background from 11 studies and followed up 6 single nucleotide polymorphisms (SNPs) in 3 replication studies of 2,198 cases and 4,918 controls. Results and conclusions: Two loci on the regions of 2p21 and 11q13.3 were associated with RCC susceptibility below genome-wide significance. Two correlated variants (r² = 0.99 in controls), rs11894252 and rs7579899, map to EPAS1 on 2p21, which encodes hypoxia-inducible-factor-2 alpha, a transcription factor previously implicated in RCC. The second locus, rs7105934, at 11q13.3, contains no characterized genes. In addition, the researchers observed a promising association on 12q24.31 for rs4765623, which maps to SCARB1, the scavenger receptor class B, member 1 gene. This study reports previously unidentified genomic regions associated with RCC risk that may lead to new etiological insights. (Purdue MP, Johansson M, Zelenika D, et al. Genome-wide association study of renal cell carcinoma identifies two susceptibility loci on 2p21 and 11q13.3. Nat Genet 2011;43:60–65)

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Second Cancers

Effects of Radiotherapy

Purpose: To estimate the proportion of second cancers attributable to radiotherapy in adults. Methods: The authors analyzed 15 cancer sites routinely treated with radiotherapy. The study cohort comprised patients aged 20 years or older and diagnosed with a first primary invasive solid cancer reported to nine SEER registries between 1973 and 2002. Results and conclusions: Among 647,672 cancer patients who were 5-year survivors followed up for a mean of 12 years, 60,271 (9%) developed a second solid cancer. For each of the first cancer sites, the relative risk (RR) of developing a second cancer associated with radiotherapy exceeded 1.0 and varied from 1.08 after cancers of the eye and orbit to 1.43 after cancer of the testes. In general, the RR was highest for organs that received more than 5 Gy, decreased with increasing age at diagnosis, and increased with time since diagnosis. The authors estimated that 3,266 excess second solid cancers could be related to radiotherapy, or 8% of the total in all radiotherapy patients surviving at least 1 year, and 5 excess cancers per 1,000 patients treated with radiotherapy by 15 years after diagnosis (see Figure 3). (Berrington de González A, Curtis RE, Kry SF, et al. Proportion of second cancers attributable to radiotherapy treatment in adults: A cohort study in the U.S. SEER cancer registries. Lancet Oncol 2011;12:353–360)

Risks After Lymphoma Subtypes

Purpose and methods: To evaluate second cancer risks among 43,145 one-year survivors of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), diffuse large B-cell lymphoma (DLBCL), or follicular lymphoma (FL) from 11 SEER population- based registries during 1992–2006. Results and conclusions: Among patients without HIV/AIDS-related lymphoma, lung cancer risks were elevated after CLL/SLL and FL but not after DLBCL (standardized incidence ratio [SIR]: CLL/SLL = 1.42, FL = 1.28). A similar pattern was observed for risk of cutaneous melanoma (SIR: CLL/SLL = 1.92, FL = 1.60). Acute non-lymphocytic leukemia risks were significantly elevated after FL and DLBCL, particularly among patients receiving initial chemotherapy, but not after CLL/SLL (SIR: FL = 5.96, DLBCL = 4.96, CLL/SLL = 1.13). Patients with HIV/AIDS-related lymphoma (n = 932) were predominantly diagnosed with DLBCL and had substantially elevated risks for second anal cancer (SIR = 120.50) and KS (SIR = 138.90). These findings suggest that differing immunologic alterations, treatments (e.g., alkylating agent chemotherapy), genetic susceptibilities, and other risk factors (e.g., viral infections, tobacco use) among lymphoma subtypes contribute to the patterns of second malignancy risk. (Morton LM, Curtis RE, Linet MS, et al. Second malignancy risks after non-Hodgkin lymphoma and chronic lymphocytic leukemia: Differences by lymphoma subtype. J Clin Oncol 2010;28:4935–4944)

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Thyroid Cancer

Chernobyl Accident–related Thyroid Cancer in Belarus

Purpose: To evaluate the radiation dose-response for prevalent thyroid cancers diagnosed during the first round of screening in Belarus after the Chernobyl nuclear accident. Methods: The authors screened 11,970 individuals aged 18 years or younger at the time of the accident, who had estimated iodine-131 (I-131) thyroid doses based on individual thyroid activity measurements and dosimetric data from questionnaires. The excess OR per gray (EOR/Gy) was modeled using linear and linear-exponential functions. Results and conclusions: For thyroid doses less than 5 Gy, the dose-response was linear (n = 85, EOR/Gy = 2.15, CI = 0.81–5.47), but at higher doses, the excess risk fell. The EOR/Gy was increased among those with prior or screening-detected diffuse goiter and was larger (although not statistically significant) for men than women and for persons exposed before age 5 than those exposed between 5 and 18 years. Ten to 15 years after the Chernobyl accident, thyroid cancer risk was increased among individuals exposed to fallout as children or adolescents, but the risk appeared lower than in other Chernobyl studies and studies of childhood external irradiation. (Zablotska LB, Ron E, Rozhko AV, et al. Thyroid cancer risk in Belarus among children and adolescents exposed to radioiodine after the Chornobyl accident. Br J Cancer 2011;104:181–187)

Chernobyl Accident–related Thyroid Cancer in Ukraine

Purpose: To evaluate the dose-response for Chernobyl accident–related incident thyroid cancers using measurement-based individual I-131 thyroid dose estimates in a prospective analytic cohort study. Methods: The cohort consists of individuals aged less than 18 years on April 26, 1986, who resided in three contaminated oblasts (states) of Ukraine and underwent up to four thyroid-screening examinations between 1998 and 2007 (N = 12,514). I-131 thyroid doses were estimated based on individual radioactivity measurements taken within two months after the accident, environmental transport models, and interview data. Results and conclusions: There were 65 incident thyroid cancers diagnosed during the second and fourth screenings and 73,004 person-years of observation. The dose-response was consistent with linearity on relative and absolute scales, although the excess relative risk (ERR) model described data better than the excess absolute risk (EAR) model. The ERR per Gy was 1.91 (CI = 0.43–6.34) and EAR per 104 person-years per Gy was 2.21 (CI = 0.04–5.78). The ERR per Gy varied significantly by oblast of residence but not by time since exposure, use of iodine prophylaxis, iodine status, sex, age, or tumor size. I-131–related thyroid cancer risks persisted for two decades following exposure with no evidence of decrease during the observation period. (Brenner AV, Tronko MD, Hatch M, et al. I-131 dose-response for incident thyroid cancers in Ukraine related to the Chornobyl accident. Environ Health Perspect 2011;119:933–939)

Iodine-131 from Nevada Nuclear Bomb Tests

Purpose: To investigate the effects of exposure to radioactive iodine from atmospheric nuclear tests conducted in Nevada in the 1950s. Methods: The authors analyzed data on thyroid cancer incidence (18,545 cases) from eight SEER tumor registries for the period 1973–2004. Excess relative risks (ERRs) per Gy for exposure received before age 15 were estimated by relating age-, birth year-, sex-, and county-specific thyroid cancer rates to estimates of cumulative dose to the thyroid that take age into account. Results and conclusions: The estimated ERR per Gy for dose received before 1 year of age was 1.8 (CI = 0.5–3.2). There was no evidence that this estimate declined with follow-up time or that risk increased with dose received at ages 1–15. (Gilbert ES, Huang L, Bouville A, et al. Thyroid cancer rates and 131I doses from Nevada atmospheric nuclear bomb tests: An update. Radiat Res 2010;173:659–664)

Effects of Body Mass Index

Purpose: To clarify the relationship between obesity and thyroid cancer. Methods: The researchers examined the association between BMI and thyroid cancer risk in a pooled analysis of five prospective U.S. studies, including 413,979 women and 434,953 men. Results and conclusions: Over a mean 10.3 years of follow-up, 768 women and 388 men were diagnosed with thyroid cancer. Risk was greater with increasing BMI per 5 kg/m² increase (HR in women = 1.16, HR in men = 1.21, CI = 0.97–1.49). For women and men combined, the HRs for overweight (25.0–29.9 kg/m²) and obesity (≥ 30 kg/m²) compared with normal weight (18.5–24.9 kg/m²) were 1.20 and 1.53, respectively. A significant positive association for BMI in young adulthood (ages 18–20) with thyroid cancer risk was also observed (per 5 kg/m² increase: HR = 1.18). (Kitahara CM, Platz EA, Freeman LE, et al. Obesity and thyroid cancer risk among U.S. men and women: A pooled analysis of five prospective studies. Cancer Epidemiol Biomarkers Prev 2011;20:464–472)

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Search DCEG Linkage



  • BMI: body mass index
  • CI: confidence interval
  • HR: hazard ratio
  • KS: Kaposi sarcoma
  • NHL: non-Hodgkin lymphoma
  • OR: odds ratio
  • SEER: Surveillance, Epidemiology and End Results

Note: This glossary defines acronyms that occur in more than one summary throughout the Scientific Highlights section.