Bingshu E Chen

Publications (29)181.62 Total impact

• Article: Epidemiology of Inflammatory Breast Cancer (IBC).

  William F Anderson, Catherine Schairer, Bingshu E Chen, Kenneth W Hance, Paul H Levine
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  ABSTRACT: Inflammatory breast cancer (IBC) is a rare and aggressive form of breast cancer with unknown etiology and generally poor outcome. It is characterized by diffuse edema (peau d'orange) and redness (erythema), although either the disease itself or case definitions have varied over time and place, confounding temporal trends and geographic variations. In this review, we discuss case definitions for IBC and its clinical characteristics; describe its geographic variation, age and racial distribution, incidence and survival patterns, and summarize the very limited information on its epidemiologic risk factors. We also incorporate emerging data from the National Cancer Institute's (NCI) Surveillance, Epidemiology, and End Results (SEER) Program.
  Breast disease 10/2009; 22:9-23.
• Source

  Available from: Roel Vermeulen

  Article: Coal use, stove improvement, and adult pneumonia mortality in Xuanwei, China: a retrospective cohort study.

  Min Shen, Robert S Chapman, Roel Vermeulen, Linwei Tian, Tongzhang Zheng, Bingshu E Chen, Eric A Engels, Xingzhou He, Aaron Blair, Qing Lan
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  ABSTRACT: In Xuanwei County, China, unvented indoor coal burning is strongly associated with increased risk of lung cancer and chronic obstructive pulmonary disease. However, the impact of coal burning and stove improvement on risk of pneumonia is not clear. We conducted a retrospective cohort study among all farmers born 1917 through 1951 and living in Xuanwei as of 1 January 1976. The analysis included a total of 42,422 cohort members. Follow-up identified all deaths in the cohort from 1976 through 1996. Ages at entry into and at exit from follow-up ranged from 24 to 59 years and from 25 to 80 years, respectively. The record search detected 225 deaths from pneumonia, and 32,332 (76%) were alive as of 31 December 1996. We constructed multivariable Cox models (time variable = age) to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Use of coal, especially smokeless coal, was positively associated with pneumonia mortality. Annual tonnage and lifetime duration of smoky and smokeless coal use were positively associated with pneumonia mortality. Stove improvement was associated with a 50% reduction in pneumonia deaths (smoky coal users: HR, 0.521; 95% CI, 0.340-0.798; smokeless coal users: HR, 0.449; 95% CI, 0.215-0.937). Our analysis is the first to suggest that indoor air pollution from unvented coal burning is an important risk factor for pneumonia death in adults and that improving ventilation by installing a chimney is an effective measure to decrease it.
  Environmental Health Perspectives 03/2009; 117(2):261-6. · 7.04 Impact Factor
• Article: The authors replied as follows:.

  Bingshu E Chen, Joan L Kramer, Mark H Greene, Philip S Rosenberg
  Biometrics 01/2009; 64(4):1297-8. · 1.83 Impact Factor
• Source

  Available from: Yu-Tang Gao

  Article: Variants in hormone-related genes and the risk of biliary tract cancers and stones: a population-based study in China.

  Sue K Park, Gabriella Andreotti, Lori C Sakoda, Yu-Tang Gao, Asif Rashid, Jinbo Chen, Bingshu E Chen, Philip S Rosenberg, Ming-Chang Shen, Bing-Sheng Wang, Tian-Quan Han, Bai-He Zhang, Meredith Yeager, Stephen Chanock, Ann W Hsing
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  ABSTRACT: Biliary tract cancers, encompassing gallbladder, extrahepatic bile duct and ampulla of Vater cancers, are uncommon but often fatal malignancies. Hormone-related factors, including parity, oral contraceptive use, obesity, and gallstones, have been implicated in the etiology of these cancers. To further clarify the role of hormones in biliary tract cancers and biliary stones, we genotyped 18 single-nucleotide polymorphisms (SNPs) in nine genes involved in steroid hormone biosynthesis, metabolism and transport in a population-based case-control study in Shanghai, China. This study included subjects who completed an interview and provided blood, which totaled 411 biliary tract cancer and 893 biliary stone patients and 786 healthy Shanghai residents. The CYP1A1 IVS1 + 606 (rs2606345) T allele was associated with gallbladder [odds ratio (OR) = 2.0, 95% confidence interval (CI), 1.3-3.0] and bile duct cancers (OR = 1.8, 95% CI = 1.1-3.1), whereas the CYP1A1 Ex7 + 131 (rs1048943) G allele was associated with ampulla of Vater cancer (OR = 2.9, 95% CI = 1.5-5.4). After taking into account multiple comparisons for SNPs within each gene, CYP1A1 was significantly associated with gallbladder (P = 0.004) and ampulla of Vater cancers (P = 0.01), but borderline with bile duct cancer (P = 0.06). The effect of CYP1A1 IVS1 + 606 on gallbladder cancer was more pronounced among non-obese (body mass index < 23) (OR = 3.3, 95% CI = 1.8-6.1; P interaction = 0.001). Among women taking oral contraceptives, the effect of SHBG Ex8 + 6 (rs6259) on gallbladder cancer (OR = 6.7, 95% CI = 2.2-20.5; P interaction = 0.001) and stones (OR = 2.3, 95% CI = 1.1-4.9; P-interaction = 0.05) was statistically significant. Our findings suggest that common variants in hormone-related genes contribute to the risk of biliary tract cancers and stones, possibly by modulating hormone metabolism.
  Carcinogenesis 01/2009; 30(4):606-14. · 5.70 Impact Factor
• Source

  Available from: aacrjournals.org

  Article: Variants in inflammation genes and the risk of biliary tract cancers and stones: a population-based study in China.

  Ann W Hsing, Lori C Sakoda, Asif Rashid, Gabriella Andreotti, Jinbo Chen, Bin-Shen Wang, Ming-Chang Shen, Bingshu E Chen, Philip S Rosenberg, Mingdong Zhang, Shelley Niwa, Lisa Chu, Robert Welch, Meredith Yeager, Joseph F Fraumeni, Yu-Tang Gao, Stephen J Chanock
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  ABSTRACT: To evaluate the role of chronic inflammation in the development of gallstones and biliary tract cancer, we examined the risk associated with 62 single nucleotide polymorphisms (SNPs), in 22 inflammation-related genes, in a population-based case-control study conducted in Shanghai, China, where the incidence of biliary tract cancer has been increasing in recent decades. The study included 411 cases with biliary tract cancer (237 gallbladder, 127 extrahepatic bile duct, and 47 ampulla of Vater), 895 with biliary stones, and 786 controls randomly selected from the population. Unconditional logistic regression was used to calculate odds ratios and 95% confidence intervals for the association of individual SNPs and haplotypes with biliary stones and biliary tract cancer. Of the 62 SNPs examined, 14 were related to the risk of biliary cancer and stones. Specifically, variants in the IL8, IL8RB, RNASEL, and NOS2 genes were associated with biliary stones, whereas VEGF variants were associated with gallbladder cancer. Of the 10 genes with multiple SNPs from which we inferred haplotypes, only one IL8RB haplotype, consisting of 3 SNPs (rs2230054, rs1126579, and rs1126580), was associated with the risk of bile duct cancer (P = 0.003) and biliary stones (P = 0.02), relative to the most frequent haplotype. In summary, common variants in genes that influence inflammatory responses may predispose to gallstones and biliary tract cancer, suggesting the need for future studies into the immunologic and inflammatory pathways that contribute to biliary diseases, including cancer.
  Cancer Research 09/2008; 68(15):6442-52. · 7.86 Impact Factor
• Source

  Available from: PubMed Central

  Article: Polymorphism of genes related to insulin sensitivity and the risk of biliary tract cancer and biliary stone: a population-based case-control study in Shanghai, China.

  Shih-Chen Chang, Asif Rashid, Yu-Tang Gao, Gabriella Andreotti, Ming-Chang Shen, Bin-Sheng Wang, Tian-Quan Han, Bai-He Zhang, Lori C Sakoda, Michael F Leitzmann, Bingshu E Chen, Philip S Rosenberg, Jinbo Chen, Stephen J Chanock, Ann W Hsing
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  ABSTRACT: Biliary tract cancer, encompassing tumors of the gallbladder, extrahepatic bile ducts and ampulla of Vater, is a rare but highly fatal malignancy. Obesity and gallstones, both related to insulin resistance, are linked to an elevated risk of biliary cancer. The peroxisome proliferator-activated receptors (PPARs) and the retinoid X receptors (RXRs), expressed in adipose tissue, play a key role in the regulation of obesity-related insulin sensitivity, thus genetic variants of these two receptor genes may be related to biliary cancer and stones. We examined the associations of seven single-nucleotide polymorphisms in the PPAR-gamma, PPAR-delta, RXR-alpha, RXR-beta and INS genes with biliary cancer and stones in a population-based case-control study in Shanghai, China. We included 237 gallbladder, 127 extrahepatic bile duct and 47 ampulla of Vater cancer cases, 895 stone cases and 786 population controls. Relative to individuals with the RXR-beta C51T (rs2076310) CC genotype, those having the TT genotype had a 1.6-fold risk for bile duct cancer [odds ratio (OR) = 1.67; 95% confidence interval (CI) = 0.99-2.84], with a more pronounced association among men (OR = 2.30; 95% CI = 1.14-4.65; P interaction = 0.07). This marker was also associated with a higher risk of gallstones among subjects with a higher body mass index (BMI) (>or=23 kg/m(2)) (OR = 1.80; 95% CI = 1.09-2.94), although the interaction with BMI was not statistically significant (P interaction = 0.28). No association was found between other variants and biliary cancers and stones. Results from this population-based study suggest that certain genetic variants involved in the regulation of obesity-related insulin sensitivity may increase susceptibility to bile duct cancer and gallstones.
  Carcinogenesis 06/2008; 29(5):944-8. · 5.70 Impact Factor
• Article: Competing risks analysis of correlated failure time data.

  Bingshu E Chen, Joan L Kramer, Mark H Greene, Philip S Rosenberg
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  ABSTRACT: We develop methods for competing risks analysis when individual event times are correlated within clusters. Clustering arises naturally in clinical genetic studies and other settings. We develop a nonparametric estimator of cumulative incidence, and obtain robust pointwise standard errors that account for within-cluster correlation. We modify the two-sample Gray and Pepe-Mori tests for correlated competing risks data, and propose a simple two-sample test of the difference in cumulative incidence at a landmark time. In simulation studies, our estimators are asymptotically unbiased, and the modified test statistics control the type I error. The power of the respective two-sample tests is differentially sensitive to the degree of correlation; the optimal test depends on the alternative hypothesis of interest and the within-cluster correlation. For purposes of illustration, we apply our methods to a family-based prospective cohort study of hereditary breast/ovarian cancer families. For women with BRCA1 mutations, we estimate the cumulative incidence of breast cancer in the presence of competing mortality from ovarian cancer, accounting for significant within-family correlation.
  Biometrics 04/2008; 64(1):172-9. · 1.83 Impact Factor
• Source

  Available from: aacrjournals.org

  Article: Polymorphisms of genes in the lipid metabolism pathway and risk of biliary tract cancers and stones: a population-based case-control study in Shanghai, China.

  Gabriella Andreotti, Jinbo Chen, Yu-Tang Gao, Asif Rashid, Bingshu E Chen, Philip Rosenberg, Lori C Sakoda, Jie Deng, Ming-Chang Shen, Bing-Sheng Wang, Tian-Quan Han, Bai-He Zhang, Meredith Yeager, Robert Welch, Stephen Chanock, Joseph F Fraumeni, Ann W Hsing
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  ABSTRACT: Biliary tract cancers, encompassing the gallbladder, extrahepatic bile duct, and ampulla of Vater, are uncommon yet highly fatal malignancies. Gallstones, the primary risk factor for biliary cancers, are linked with hyperlipidemia. We examined the associations of 12 single nucleotide polymorphisms of five genes in the lipid metabolism pathway with the risks of biliary cancers and stones in a population-based case-control study in Shanghai, China. We included 235 gallbladder, 125 extrahepatic bile duct, and 46 ampulla of Vater cancer cases, 880 biliary stone cases, and 779 population controls. Subjects completed an in-person interview and gave blood. Genotyping was conducted by TaqMan assay using DNA from buffy coats. The effects of APOE IVS1+69 (rs440446) and APOB IVS6+360C>T (rs520354) markers were limited to men. Men carrying the G allele of APOE IVS1+69 had a 1.7-fold risk of stones [95% confidence interval (95% CI), 1.2-2.4], a 1.8-fold risk of gallbladder cancer (95% CI, 1.0-3.3), a 3.7-fold risk of bile duct cancer (95% CI, 2.0-7.0), and a 4-fold risk of ampullary cancer (95% CI, 1.4-12.4). Male carriers of the T allele of APOB IVS6+360C>T had a 2-fold risk of bile duct cancer (95% CI, 1.2-3.4). The APOB T-T haplotype (APOB IVS6+360C>T, EX4+56C>T) was associated with a 1.6-fold risk of bile duct cancer (95% CI, 1.1-2.3). Male and female carriers of the T allele of LDLR IVS9-30C>T (rs1003723) had a 1.5-fold risk of bile duct cancer. Our findings suggest that gene variants in the lipid metabolism pathway contribute to the risk of biliary tract stones and cancers, particularly of the bile duct.
  Cancer Epidemiology Biomarkers &amp Prevention 03/2008; 17(3):525-34. · 4.12 Impact Factor
• Article: Polymorphic variants in PTGS2 and prostate cancer risk: results from two large nested case-control studies.

  Kim N Danforth, Richard B Hayes, Carmen Rodriguez, Kai Yu, Lori C Sakoda, Wen-Yi Huang, Bingshu E Chen, Jinbo Chen, Gerald L Andriole, Eugenia E Calle, Eric J Jacobs, Lisa W Chu, Jonine D Figueroa, Meredith Yeager, Elizabeth A Platz, Dominique S Michaud, Stephen J Chanock, Michael J Thun, Ann W Hsing
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  ABSTRACT: Chronic inflammation has been hypothesized to increase prostate cancer risk. Prostaglandin-endoperoxide synthase 2 (PTGS2) encodes the proinflammatory cyclooxygenase 2 enzyme believed to be the rate-limiting step in the synthesis of prostaglandins, important mediators of inflammation. We investigated associations between PTGS2 polymorphisms and prostate cancer risk among 2321 prostate cancer cases and 2560 controls in two large case-control studies nested within the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial and the Cancer Prevention Study II Nutrition Cohort. Five single nucleotide polymorphisms (SNPs) (rs5277, rs20432, rs4648276, rs5275 and rs689470) were examined in SNP and haplotype analyses (five SNPs in PLCO and four SNPs in the Nutrition Cohort). In PLCO, the Ex10 +837 T>C marker (rs5275) was initially associated with prostate cancer risk (P-trend = 0.02) but became non-significant after adjustment for multiple comparisons (P = 0.08); this SNP showed no association with prostate cancer risk in the Nutrition Cohort (P-trend = 0.54) or in an analysis pooling the two cohorts (P-trend = 0.20). No other SNP was associated with prostate cancer risk in PLCO or the Nutrition Cohort individually or combined. Haplotype analyses suggested an association between PTGS2 variants in PLCO alone (global P = 0.007), but not in the Nutrition Cohort (global P = 0.78) or pooled analysis (global P = 0.18). In conclusion, despite the potential importance of inflammation in prostate carcinogenesis, results from our large study of five PTGS2 SNPs does not support a strong association between PTGS2 variants and prostate cancer risk in non-Hispanic white men.
  Carcinogenesis 03/2008; 29(3):568-72. · 5.70 Impact Factor
• Article: TNF polymorphisms and prostate cancer risk.

  Kim N Danforth, Carmen Rodriguez, Richard B Hayes, Lori C Sakoda, Wen-Yi Huang, Kai Yu, Eugenia E Calle, Eric J Jacobs, Bingshu E Chen, Gerald L Andriole, Jonine D Figueroa, Meredith Yeager, Elizabeth A Platz, Dominique S Michaud, Stephen J Chanock, Michael J Thun, Ann W Hsing
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  ABSTRACT: Inflammation has been hypothesized to increase prostate cancer risk. Tumor necrosis factor (TNF) is an important mediator of the inflammatory process, but the relationship between TNF variants and prostate cancer remains unclear. We examined associations between six TNF single nucleotide polymorphisms (SNPs) (rs1799964, rs1800630, rs1799724, rs1800629, rs361525, rs1800610) and prostate cancer risk among 2,321 cases and 2,560 controls from two nested case-control studies within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO, n = 2,561, 5 SNPs) and the Cancer Prevention Study II Nutrition Cohort (Nutrition Cohort, n = 2,320, 6 SNPs). Odds ratios and 95% confidence intervals were estimated for individual SNPs and haplotypes in each cohort separately and in pooled analyses. No TNF SNP was associated with prostate cancer risk in PLCO (P-trend > or = 0.16), while in the Nutrition Cohort, associations were significant for 2 highly correlated variants (rs1799724, 1800610, r2 = 0.95; P-trend = 0.04 and 0.02, respectively). In pooled analyses, no single SNP was associated with prostate cancer risk (P-trend > or = 0.08). After adjustment for multiple testing, no SNP was associated with prostate cancer risk in either cohort individually or in the pooled analysis (P-trend all > or = 0.10). Haplotypes based on 5 TNF SNPs did not vary by case/control status in PLCO, but showed marginal associations in the Nutrition Cohort (global P = 0.06) and the pooled analysis (global P = 0.05). Despite somewhat suggestive haplotype results, overall our study does not support an association between TNF variants and prostate cancer risk.
  The Prostate 03/2008; 68(4):400-7. · 3.48 Impact Factor
• Source

  Available from: Idan Menashe

  Article: PGA: power calculator for case-control genetic association analyses.

  Idan Menashe, Philip S Rosenberg, Bingshu E Chen
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  ABSTRACT: Statistical power calculations inform the design and interpretation of genetic association studies, but few programs are tailored to case-control studies of single nucleotide polymorphisms (SNPs) in unrelated subjects. We have developed the "Power for Genetic Association analyses" (PGA) package which comprises algorithms and graphical user interfaces for sample size and minimum detectable risk calculations using SNP or haplotype effects under different genetic models and study constrains. The software accounts for linkage disequilibrium and statistical multiple comparisons. The results are presented in graphs or tables and can be printed or exported in standard file formats. PGA is user friendly software that can facilitate decision making for association studies of candidate genes, fine-mapping studies, and whole-genome scans. Stand-alone executable files and a Matlab toolbox are available for download at: http://dceg.cancer.gov/bb/tools/pga.
  BMC Genetics 02/2008; 9:36. · 2.47 Impact Factor
• Article: Selected base excision repair gene polymorphisms and susceptibility to biliary tract cancer and biliary stones: a population-based case-control study in China.

  Wen-Yi Huang, Yu-Tang Gao, Asif Rashid, Lori C Sakoda, Jie Deng, Ming-Chang Shen, Bin-Sheng Wang, Tian-Quan Han, Bai-He Zhang, Bingshu E Chen, Philip S Rosenberg, Stephen J Chanock, Ann W Hsing
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  ABSTRACT: Base excision repair (BER) corrects DNA damage caused by oxidative stress and chronic inflammation, putative risk factors for cancer. To understand the relationship between genetic variation in BER genes and risk of biliary tract cancer and biliary stones, we examined non-synonymous polymorphisms in three key BER genes-x-ray repair cross-complementing group 1 (XRCC1) (R194W, rs1799782; R280H, rs25489 and R399Q, rs25487), apurinic/apyrimidinic endonuclease (APEX1) (D148E, rs3136820) and 8-oxoguanine DNA glycosylase (OGG1) (S326C, rs1052133), in a population-based study of 411 biliary tract cancer cases (237 gallbladder, 127 bile duct and 47 ampulla of Vater), 891 biliary (gallbladder or bile duct) stone cases and 786 population controls conducted in Shanghai, China. Compared with subjects carrying the XRCC1 194RR genotype, those with the WW genotype had a 1.9-fold risk of bile duct cancer [odds ratio (OR) = 1.9, 95% confidence interval (CI) = 1.1-3.5, P(trend) = 0.03], and compared with subjects carrying the XRCC1 280RR genotype, those with the XRCC1 280H allele had a 50% reduced risk of bile duct cancer (OR = 0.5, 95% CI = 0.3-0.9, P(trend) = 0.05). The effect of the R280H polymorphism persisted (P(trend) = 0.03), when all three XRCC1 polymorphisms were jointly considered in the model, a finding supported by the haplotype results (covariate-adjusted global permutation P = 0.03). We also found an inverse association between the APEX1 148E allele and gallbladder stones (P(trend) = 0.03), but no association for the OGG1 polymorphism. This study suggests that genetic variants in XRCC1 and APEX1 may alter susceptibility to biliary tract cancer and stones. Further studies are required to confirm the reported associations.
  Carcinogenesis 02/2008; 29(1):100-5. · 5.70 Impact Factor
• Article: Risk of second non-hematological malignancies among 376,825 breast cancer survivors.

  Linda Morris Brown, Bingshu E Chen, Ruth M Pfeiffer, Catherine Schairer, Per Hall, Hans Storm, Eero Pukkala, Frøydis Langmark, Magnus Kaijser, Michael Andersson, Heikki Joensuu, Sophie D Fosså, Lois B Travis
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  ABSTRACT: Breast cancer survivors are at increased risk of treatment-related second cancers. This study is the first to examine risk 30 or more years after diagnosis and to present absolute risks of second cancer which accounts for competing mortality. We identified 23,158 second non-hematological malignancies excluding breast in a population-based cohort of 376,825 one-year survivors of breast cancer diagnosed from 1943 to 2002 and reported to four Scandinavian cancer registries. We calculated standardized incidence ratios (SIR) and utilized a competing-risk model to calculate absolute risk of developing second cancers. The overall SIR for second cancers was 1.15 (95% confidence interval [CI] = 1.14-1.17). The SIR for potentially radiotherapy-associated cancers 30 or more years after breast cancer diagnosis was 2.19 (95% CI = 1.87-2.55). However, the largest SIRs were observed for women aged <40 years followed for 1-9 years. At 20 years after breast cancer diagnosis, the absolute risk of developing a second cancer ranged from 0.6 to 10.3%, depending on stage and age; the difference in the absolute risk compared to the background population was greatest for women aged <40 years with localized disease, 2.3%. At 30 years post breast cancer diagnosis, this difference reached 3.2%. These risks were small compared to the corresponding risk of dying from breast cancer. Although the absolute risks were small, we found persistent risks of second non-hematological malignancies excluding breast 30 or more years after breast cancer diagnosis, particularly for women diagnosed at young ages with localized disease.
  Breast Cancer Research and Treatment 01/2008; 106(3):439-51. · 4.43 Impact Factor
• Article: Qualitative age interactions (or effect modification) suggest different cancer pathways for early-onset and late-onset breast cancers.

  William F Anderson, Bingshu E Chen, Louise A Brinton, Susan S Devesa
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  ABSTRACT: Prior to 1999-2000, breast cancer incidence rates had risen for decades, though more among older than younger women. To further explore the impact of advancing age-at-diagnosis upon breast cancer incidence, we used the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program (1974-2003). Over time, we observed age interactions by tumor grade, stage, and race. For example, among women ages <40 years, high-grade lesions were more common than low-grade tumors for all time periods. Among women ages 40+ years, high-grade lesions were more common during early time periods then trend lines crossed, after which low-grade tumors were more common than high-grade lesions. Notably, the transition (crossover point) occurred earlier with advancing age-at-diagnosis. The reversal (crossing) of incidence rates from high to low-grade tumors among women 40+ years is a qualitative age interaction, probably due to changing age-related risk factor and/or screening patterns, where mammography preferentially detected tumors of low malignant potential among older women. Though once thought to be rare or artifactual, qualitative age interactions suggest breast cancer heterogeneity. Indeed, if real, qualitative age interactions (effect modifications) imply different etiologic pathways for early-onset and late-onset types of breast cancer.
  Cancer Causes and Control 12/2007; 18(10):1187-98. · 2.88 Impact Factor
• Article: Leukemia following breast cancer: an international population-based study of 376,825 women.

  Regan A Howard, Ethel S Gilbert, Bingshu E Chen, Per Hall, Hans Storm, Eero Pukkala, Froydis Langmark, Magnus Kaijser, Michael Andersson, Heikki Joensuu, Sophie D Fossa, Lois B Travis
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  ABSTRACT: To quantify long-term temporal trends in the excess absolute risk (EAR) of secondary leukemia among breast cancer (BC) survivors, using multivariate analyses to evaluate the effects of subtype, age at BC diagnosis, attained age, and calendar year. We identified 376,825 1-year survivors of BC within 4 nationwide, population-based cancer registries in Sweden, Denmark, Finland, and Norway (1943-2001). Estimates of EAR (per 100,000 person-years) were modeled using Poisson regression methods and cumulative risks calculated using a competing risk model. A total of 687 non-chronic lymphocytic leukemias (EAR = 9.05; 95% confidence interval (CI) = 7.5-10.7) was reported. Significantly elevated risks were observed for the first time for chronic myeloid leukemia (CML) (EAR = 2.06; 95% CI = 1.3-2.9) and acute lymphoblastic leukemia (ALL) (EAR = 0.62; 95% CI = 0.2-1.1), in addition to acute myeloid leukemia (AML) (EAR = 5.00; 95% CI = 3.9-6.2). Excesses of CML, ALL, AML and all leukemias combined persisted over 25 years after BC diagnosis. For all leukemias, EAR decreased with increasing calendar year (P = 0.04) of BC diagnosis. Risk for all leukemia and AML by calendar year of BC diagnosis depended on age at diagnosis. For women diagnosed with BC after 1985, the 10-year cumulative risk of leukemia for those diagnosed before and after age 50 was small, 0.10% and 0.14%, respectively. Although secondary leukemia is a rare event, BC survivors experience statistically significant excesses for at least 25 years after diagnosis, including CML and ALL. Decreasing leukemia risks in recent calendar years likely reflect changes in treatment.
  Breast Cancer Research and Treatment 12/2007; 105(3):359-68. · 4.43 Impact Factor
• Article: Second cancers among 104,760 survivors of cervical cancer: evaluation of long-term risk.

  Anil K Chaturvedi, Eric A Engels, Ethel S Gilbert, Bingshu E Chen, Hans Storm, Charles F Lynch, Per Hall, Froydis Langmark, Eero Pukkala, Magnus Kaijser, Michael Andersson, Sophie D Fosså, Heikki Joensuu, John D Boice, Ruth A Kleinerman, Lois B Travis
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  ABSTRACT: Given the extended survival of patients diagnosed with cervical cancer, the large number of these women treated with radiotherapy, and the presence in this population of established cancer risk factors such as human papillomavirus (HPV) infection and cigarette smoking, it is important to clarify long-term trends in second cancer risk. Using data from 104,760 one-year survivors of cervical cancer reported to 13 population-based cancer registries in Denmark, Finland, Norway, Sweden, and the United States, we calculated standardized incidence ratios (SIRs) for second cancers overall and cancers at particular sites among women with cervical cancer, including cervical cancer patients who were treated or not treated with radiation, over more than 40 years of follow-up. Cox regression models were used to assess the time-varying association of radiotherapy with risk of second cancers and to assess the interaction of radiation treatment with age at diagnosis. All statistical tests were two-sided. Among 104,760 one-year survivors of cervical cancer, the risk of all second cancers taken together was increased to a statistically significant extent (n = 12,496; SIR = 1.30; 95% confidence interval [CI] = 1.28 to 1.33). Compared with the general population, in both radiotherapy (N = 52,613) and no-radiotherapy groups (N = 27,382), risks for HPV-related cancers (of the pharynx, genital sites, and rectum/anus) and smoking-related cancers (of the pharynx, trachea/bronchus/lung, pancreas, and urinary bladder) were elevated to a statistically significant extent. Cervical cancer patients treated with radiotherapy, but not those who did not receive radiotherapy, were at increased risk for all second cancers and cancers at heavily irradiated sites (colon, rectum/anus, urinary bladder, ovary, and genital sites) beyond 40 years of follow-up compared with women in the general population. The association of radiotherapy with second cancer risk was modified by age at cervical cancer diagnosis for rectum/anus, genital sites, and urinary bladder, with higher hazard ratios for second cancer at younger ages of cervical cancer. After adjustment for competing mortality, the 40-year cumulative risk of any second cancer was higher among women diagnosed with cervical cancer before age 50 (22.2%; 95% CI = 21.5% to 22.8%) than among women diagnosed after age 50 (16.4%; 95% CI = 16.1% to 16.9%). Cervical cancer patients treated with radiotherapy are at increased risk of second cancers at sites in close proximity to the cervix beyond 40 years of follow-up.
  CancerSpectrum Knowledge Environment 12/2007; 99(21):1634-43. · 14.07 Impact Factor
• Article: Comparative mortality for 621 second cancers in 29356 testicular cancer survivors and 12420 matched first cancers.

  Catherine Schairer, Michie Hisada, Bingshu E Chen, Linda M Brown, Regan Howard, Sophie D Fosså, Mitchell Gail, Lois B Travis
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  ABSTRACT: Testicular cancer survivors, many of whom have undergone radiotherapy, are at substantial risk of second cancers. Treatment for testicular cancer may limit treatment options for second cancers, thereby adversely affecting survival after the second cancer. However, no data on outcomes of testicular cancer survivors with second cancers compared to patients with comparable first cancers exist. Among 29356 white testicular cancer patients reported to the Surveillance, Epidemiology, and End Results (SEER) program (1973-2002), 621 developed a second cancer with known stage and were matched to a random sample of 12420 white male first cancer patients in the SEER program by cancer site, stage, diagnosis year, and age at diagnosis. Mortality was ascertained through 2002. Cancer-specific and all-cause mortality following second cancers were compared with those of matched first cancers, and rate ratios (RRs) were estimated using proportional hazards analysis. Survival functions were calculated using product-limit estimates. During the study period, 284 testicular cancer survivors with second cancers died, 191 from their second cancer; 5443 matched first cancer patients died, 3929 from their first cancer. Rate ratios for cancer-specific and all-cause mortality for second cancers compared with matched first cancers were 1.05 (95% confidence interval [CI] = 0.90 to 1.23) and 1.09 (95% CI = 0.96 to 1.23), respectively. However, among testicular cancer patients who were diagnosed during 1973-1979, an era in which radiation therapy was given at high doses and to the chest area, all-cause mortality following second cancers at sites below the diaphragm (79 deaths) and second lung cancers (29 deaths) was statistically significantly higher than that from matched first cancers (RR = 1.44, 95% CI = 1.13 to 1.83, and RR = 1.65, 95% CI = 1.12 to 2.42, respectively). Mortality from second cancers following testicular cancer was similar to matched first cancers, except for selected tumors in the radiotherapy field among testicular cancer patients who were diagnosed during 1973-1979, a time when radiotherapy doses for treatment of testicular cancer were high and chest irradiation was an option in standard practice.
  CancerSpectrum Knowledge Environment 09/2007; 99(16):1248-56. · 14.07 Impact Factor
• Article: Reconstruction of the hepatitis C virus epidemic in the US hemophilia population, 1940-1990.

  James J Goedert, Bingshu E Chen, Liliana Preiss, Louis M Aledort, Philip S Rosenberg
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  ABSTRACT: Hepatitis C virus (HCV) is a blood-borne infection readily transmitted by transfusion. Persons with hemophilia were at very high risk of acquiring HCV, but the chronology and correlates of HCV incidence in the US hemophilia population remain unknown. The authors used multiple data sources and new statistical methods to reconstruct HCV incidence in White males with hemophilia A from 1940 through 1990. HCV incidence was approximately 1%/year until 1950 but 2-3%/year by 1955. With mild hemophilia, HCV incidence increased in the 1960s, reaching a plateau of approximately 8%/year from 1969 to 1980. With moderate and severe hemophilia, HCV incidence increased steeply to peaks of 11.7%/year in 1970 and 17.2%/year in 1968, respectively. Overall, HCV incidence declined after 1970, steeply after 1984, to nearly zero by 1990. With improving and increasing use of plasma derivatives, the size of the hemophilia population increased 86% during these 50 years. Study results imply that these life-saving treatments also carried an increasing risk of HCV, particularly before clotting factor concentrates were licensed in the 1970s. They also suggest that multiple synergistic interventions since 1970, particularly donor deferral, screening for hepatitis B and human immunodeficiency virus, and viral inactivation of clotting factor concentrates, were needed to reduce transfusion of HCV prior to its discovery.
  American Journal of Epidemiology 07/2007; 165(12):1443-53. · 5.22 Impact Factor
• Article: Estimating age-specific breast cancer risks: a descriptive tool to identify age interactions.

  William F Anderson, Rayna K Matsuno, Mark E Sherman, Jolanta Lissowska, Mitchell H Gail, Louise A Brinton, Xiaohong Rose Yang, Beata Peplonska, Bingshu E Chen, Philip S Rosenberg, Nilanjan Chatterjee, Neonila Szeszenia-Dabrowska, Alicja Bardin-Mikolajczak, Witold Zatonski, Susan S Devesa, Montserrat García-Closas
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  ABSTRACT: Clarifying age-specific female breast cancer risks and interactions may provide important etiologic clues. Using a population-based case-control study in Poland (2000-2003) of 2,386 incident breast cancer cases and 2,502 control subjects aged 25-74 years, we estimated age-specific breast cancer incidence rates according to risk factors. Breast cancer risks were elevated among women with positive family history (FH), younger age at menarche, older age at first full-term birth, nulliparity, exogenous hormonal usage, and reduced physical activity (PA). Notwithstanding overall risks, we observed statistically significant quantitative (non-crossover) and qualitative (crossover) age interactions for all risk factors except for FH and PA. For example, nulliparity compared to parity reduced breast cancer risk among women ages 25-39 years then rates crossed or reversed, after which nulliparity increased relative risks among women ages 40-74 years. Though quantitative age interactions could be expected, qualitative interactions were somewhat counterintuitive. If confirmed in other populations, qualitative interactions for a continuous covariate such as age will be difficult to reconcile in a sequential (multistep or monolithic) 'stochastic' breast cancer model. Alternatively, the reversal of relative risks among younger and older women suggests subgroup heterogeneity with different etiologic mechanisms for early-onset and late-onset breast cancer types.
  Cancer Causes and Control 06/2007; 18(4):439-47. · 2.88 Impact Factor
• Article: Breast cancer mortality trends in the United States according to estrogen receptor status and age at diagnosis.

  Ismail Jatoi, Bingshu E Chen, William F Anderson, Philip S Rosenberg
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  ABSTRACT: Since 1990, overall breast cancer mortality rates in the United States decreased 24%. This decline has been attributed to mammography screening and adjuvant systemic therapy. However, the efficacy of these modalities may depend on estrogen receptor (ER) expression and age. We therefore examined breast cancer mortality trends in the United States according to ER status and age. Using the Surveillance, Epidemiology, and End Results (SEER) program (1990-2003), we calculated trends in incidence-based mortality (IBM), annual hazard rates for breast cancer deaths after diagnosis, and relative hazard rates for women with ER-positive and ER-negative tumors. Relative hazard rates were assessed with Cox proportional hazards models, adjusted for stage and grade, and stratified by age at diagnosis. During the study period, IBM and annual hazard rates for breast cancer deaths decreased among women with ER-positive and ER-negative tumors, although declines were greater for those with ER-positive tumors. Among women younger than 70 years, relative hazard rates declined 38% for those with ER-positive tumors versus 19% for those with ER-negative tumors. Among women 70 years or older, relative hazard rates declined 14% for those with ER-positive tumors versus no significant decline for those with ER-negative tumors. In the United States, breast cancer mortality rates have declined among women with ER-positive and ER-negative tumors, with greater declines among younger women and those with ER-positive tumors. Although mortality in all groups remains unacceptably high, additional emphasis should be placed on improving outcomes of breast cancer patients older than 70 years and those of all ages with ER-negative tumors.
  Journal of Clinical Oncology 05/2007; 25(13):1683-90. · 18.37 Impact Factor