Roy E Shore

Publications (60)229.45 Total impact

• Article: Circulating prolactin levels and risk of epithelial ovarian cancer.

  Tess V Clendenen, Alan A Arslan, Anna E Lokshin, Mengling Liu, Eva Lundin, Karen L Koenig, Franco Berrino, Goran Hallmans, Annika Idahl, Vittorio Krogh, Annekatrin Lukanova, Adele Marrangoni, Paola Muti, Brian M Nolen, Nina Ohlson, Roy E Shore, Sabina Sieri, Anne Zeleniuch-Jacquotte
  [show abstract] [hide abstract]
  ABSTRACT: PURPOSE: Indirect evidence from experimental and epidemiological studies suggests that prolactin may be involved in ovarian cancer development. However, the relationship between circulating prolactin levels and risk of ovarian cancer is unknown. METHODS: We conducted a nested case-control study of 230 cases and 432 individually matched controls within three prospective cohorts to evaluate whether pre-diagnostic circulating prolactin is associated with subsequent risk of ovarian cancer. We also assessed whether lifestyle and reproductive factors are associated with circulating prolactin among controls. RESULTS: Prolactin levels were significantly lower among post- versus pre-menopausal women, parous versus nulliparous women, and past versus never users of oral contraceptives in our cross-sectional analysis of controls. In our nested case-control study, we observed a non-significant positive association between circulating prolactin and ovarian cancer risk (OR(Q4vsQ1) 1.56, 95 % CI 0.94, 2.63, p trend 0.15). Our findings were similar in multivariate-adjusted models and in the subgroup of women who donated blood ≥5 years prior to diagnosis. We observed a significant positive association between prolactin and risk for the subgroup of women with BMI ≥25 kg/m(2) (OR(Q4vsQ1) 3.10, 95 % CI 1.39, 6.90), but not for women with BMI <25 kg/m(2) (OR(Q4vsQ1) 0.81, 95 % CI 0.40, 1.64). CONCLUSIONS: Our findings suggest that prolactin may be associated with increased risk of ovarian cancer, particularly in overweight/obese women. Factors associated with reduced risk of ovarian cancer, such as parity and use of oral contraceptives, were associated with lower prolactin levels, which suggests that modulation of prolactin may be a mechanism underlying their association with risk.
  Cancer Causes and Control 02/2013; · 2.88 Impact Factor
• Article: Selected polymorphisms in sex hormone-related genes, circulating sex hormones and risk of endometrial cancer.

  Eva Lundin, Isaac Wirgin, Annekatrin Lukanova, Yelena Afanasyeva, Vittorio Krogh, Tomas Axelsson, Kari Hemminki, Tess V Clendenen, Alan A Arslan, Nina Ohlson, [......], Karen L Koenig, Annika Idahl, Franco Berrino, Paolo Toniolo, Göran Hallmans, Asta Försti, Paola Muti, Per Lenner, Roy E Shore, Anne Zeleniuch-Jacquotte
  [show abstract] [hide abstract]
  ABSTRACT: Background: The role of estrogen and progesterone in the development of endometrial cancer is well documented. Few studies have examined the association of genetic variants in sex hormone-related genes with endometrial cancer risk. Methods: We conducted a case-control study nested within three cohorts to examine the association of endometrial cancer risk with polymorphisms in hormone-related genes among 391 cases (92% postmenopausal at diagnosis) and 712 individually-matched controls. We also examined the association of these polymorphisms with circulating levels of sex hormones and SHBG in a cross-sectional analysis including 596 healthy postmenopausal women at blood donation (controls from this nested case-control study and from a nested case-control study of breast cancer in one of the three cohorts). Results: Adjusting for endometrial cancer risk factors, the A allele of rs4775936 in CYP19 was significantly associated (OR(per allele)=1.22, 95% CI=1.01-1.47, p(trend)=0.04), while the T allele of rs10046 was marginally associated with increased risk of endometrial cancer (OR(per allele)=1.20, 95% CI=0.99-1.45, p(trend)=0.06). PGR rs1042838 was also marginally associated with risk (OR(per allele)=1.25, 95% CI=0.96-1.61, p(trend)=0.09). No significant association was found for the other polymorphisms, i.e. CYP1B1 rs1800440 and rs1056836, UGT1A1 rs8175347, SHBG rs6259 and ESR1 rs2234693. Rs8175347 was significantly associated with postmenopausal levels of estradiol, free estradiol and estrone and rs6259 with SHBG and estradiol. Conclusion: Our findings support an association between genetic variants in CYP19, and possibly PGR, and risk of endometrial cancer.
  Cancer epidemiology. 05/2012; 36(5):445-52.
• Article: Body mass index and risk of second primary breast cancer: The WECARE Study

  Jennifer D. Brooks, Esther M. John, Lene Mellemkjær, Anne S. Reiner, Kathleen E. Malone, Charles F. Lynch, Jane C. Figueiredo, Robert W. Haile, Roy E. Shore, The WECARE Study Collaborative Group, Jonine L. Bernstein, Leslie Bernstein
  [show abstract] [hide abstract]
  ABSTRACT: The identification of potentially modifiable risk factors, such as body size, could allow for interventions that could help reduce the burden of contralateral breast cancer (CBC) among breast cancer survivors. Studies examining the relationship between body mass index (BMI) and CBC have yielded mixed results. From the population-based, case–control, Women’s Environmental, Cancer and Radiation Epidemiology (WECARE) Study, we included 511 women with CBC (cases) and 999 women with unilateral breast cancer (controls) who had never used postmenopausal hormone therapy. Rate ratios (RR) and 95% confidence intervals (CI) were used to assess the relationship between BMI and CBC risk. No associations between BMI at first diagnosis or weight-change between first diagnosis and date of CBC diagnosis (or corresponding date in matched controls) and CBC risk were seen. However, obese (BMI ≥30kg/m2) postmenopausal women with estrogen receptor (ER)-negative first primary tumors (n=12 cases and 9 controls) were at an increased risk of CBC compared with normal weight women (BMI <25kg/m2) (n=43 cases and 98 controls) (RR=5.64 (95% CI 1.76, 18.1)). No association between BMI and CBC risk was seen in premenopausal or postmenopausal women with ER-positive first primaries. Overall, BMI is not associated with CBC risk in this population of young breast cancer survivors. Our finding of an over five-fold higher risk of CBC in a small subgroup of obese postmenopausal women with an ER-negative first primary breast cancer is based on limited numbers and requires confirmation in a larger study. KeywordsBMI–Second primary contralateral breast cancer–ER-negative
  Breast Cancer Research and Treatment 05/2012; 131(2):571-580. · 4.43 Impact Factor
• Article: Reproductive Status at First Diagnosis Influences Risk of Radiation-Induced Second Primary Contralateral Breast Cancer in the WECARE Study.

  Jennifer D Brooks, John D Boice, Marilyn Stovall, Anne S Reiner, Leslie Bernstein, Esther M John, Charles F Lynch, Lene Mellemkjær, Julia A Knight, Duncan C Thomas, Robert W Haile, Susan A Smith, Marinela Capanu, Jonine L Bernstein, Roy E Shore
  [show abstract] [hide abstract]
  ABSTRACT: PURPOSE: Our study examined whether reproductive and hormonal factors before, at the time of, or after radiation treatment for a first primary breast cancer modify the risk of radiation-induced second primary breast cancer. METHODS AND MATERIALS: The Women's Environmental, Cancer and Radiation Epidemiology (WECARE) Study is a multicenter, population-based study of 708 women (cases) with asynchronous contralateral breast cancer (CBC) and 1399 women (controls) with unilateral breast cancer. Radiotherapy (RT) records, coupled with anthropomorphic phantom simulations, were used to estimate quadrant-specific radiation dose to the contralateral breast for each patient. Rate ratios (RR) and 95% confidence intervals (CI) were computed to assess the relationship between reproductive factors and risk of CBC. RESULTS: Women who were nulliparous at diagnosis and exposed to ≥1 Gy to the contralateral breast had a greater risk for CBC than did matched unexposed nulliparous women (RR = 2.2; 95% CI, 1.2-4.0). No increased risk was seen in RT-exposed parous women (RR = 1.1; 95% CI, 0.8-1.4). Women treated with RT who later became pregnant (8 cases and 9 controls) had a greater risk for CBC (RR = 6.0; 95% CI, 1.3-28.4) than unexposed women (4 cases and 7 controls) who also became pregnant. The association of radiation with risk of CBC did not vary by number of pregnancies, history of breastfeeding, or menopausal status at the time of first breast cancer diagnosis. CONCLUSION: Nulliparous women treated with RT were at an increased risk for CBC. Although based on small numbers, women who become pregnant after first diagnosis also seem to be at an increased risk for radiation-induced CBC.
  International journal of radiation oncology, biology, physics 04/2012; 84(4):917-924. · 4.59 Impact Factor
• Article: Premenopausal serum androgens and breast cancer risk: a nested case-control study.

  Anne Zeleniuch-Jacquotte, Yelena Afanasyeva, Rudolf Kaaks, Sabina Rinaldi, Stephanie Scarmo, Mengling Liu, Alan A Arslan, Paolo Toniolo, Roy E Shore, Karen L Koenig
  [show abstract] [hide abstract]
  ABSTRACT: Prospective epidemiologic studies have consistently shown that levels of circulating androgens in postmenopausal women are positively associated with breast cancer risk. However, data in premenopausal women are limited. A case-control study nested within the New York University Women's Health Study was conducted. A total of 356 cases (276 invasive and 80 in situ) and 683 individually-matched controls were included. Matching variables included age and date, phase, and day of menstrual cycle at blood donation. Testosterone, androstenedione, dehydroandrosterone sulfate (DHEAS) and sex hormone-binding globulin (SHBG) were measured using direct immunoassays. Free testosterone was calculated. Premenopausal serum testosterone and free testosterone concentrations were positively associated with breast cancer risk. In models adjusted for known risk factors of breast cancer, the odds ratios for increasing quintiles of testosterone were 1.0 (reference), 1.5 (95% confidence interval (CI), 0.9 to 2.3), 1.2 (95% CI, 0.7 to 1.9), 1.4 (95% CI, 0.9 to 2.3) and 1.8 (95% CI, 1.1 to 2.9; Ptrend = 0.04), and for free testosterone were 1.0 (reference), 1.2 (95% CI, 0.7 to 1.8), 1.5 (95% CI, 0.9 to 2.3), 1.5 (95% CI, 0.9 to 2.3), and 1.8 (95% CI, 1.1 to 2.8, Ptrend = 0.01). A marginally significant positive association was observed with androstenedione (P = 0.07), but no association with DHEAS or SHBG. Results were consistent in analyses stratified by tumor type (invasive, in situ), estrogen receptor status, age at blood donation, and menopausal status at diagnosis. Intra-class correlation coefficients for samples collected from 0.8 to 5.3 years apart (median 2 years) in 138 cases and 268 controls were greater than 0.7 for all biomarkers except for androstenedione (0.57 in controls). Premenopausal concentrations of testosterone and free testosterone are associated with breast cancer risk. Testosterone and free testosterone measurements are also highly reliable (that is, a single measurement is reflective of a woman's average level over time). Results from other prospective studies are consistent with our results. The impact of including testosterone or free testosterone in breast cancer risk prediction models for women between the ages of 40 and 50 years should be assessed. Improving risk prediction models for this age group could help decision making regarding both screening and chemoprevention of breast cancer.
  Breast cancer research: BCR 02/2012; 14(1):R32. · 5.24 Impact Factor
• Article: Factors associated with inflammation markers, a cross-sectional analysis.

  Tess V Clendenen, Karen L Koenig, Alan A Arslan, Annekatrin Lukanova, Franco Berrino, Yian Gu, Goran Hallmans, Annika Idahl, Vittorio Krogh, Anna E Lokshin, Eva Lundin, Paola Muti, Adele Marrangoni, Brian M Nolen, Nina Ohlson, Roy E Shore, Sabina Sieri, Anne Zeleniuch-Jacquotte
  [show abstract] [hide abstract]
  ABSTRACT: Epidemiological studies have reported associations between circulating inflammation markers and risk of chronic diseases. It is of interest to examine whether risk factors for these diseases are associated with inflammation. We conducted a cross-sectional analysis to evaluate whether reproductive and lifestyle factors and circulating vitamin D were associated with inflammation markers, including C-reactive protein, cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p40, IL-12p70, IL-13, TNFα), and cytokine modulators (IL-1RA, sIL-1RII, sIL-2Ra, sIL-4R, sIL-6R, sTNF-R1/R2), among 616 healthy women. We confirmed associations of several inflammation markers with age and BMI. We also observed significantly higher levels of certain inflammation markers in postmenopausal vs. premenopausal women (TNFα, sIL-1RII, sIL-2Ra), with increasing parity (IL-12p40), and with higher circulating 25(OH) vitamin D (IL-13) and lower levels among current users of non-steroidal anti-inflammatory drugs (NSAIDs) (IL-1β, IL-2, IL-10, IL-12p70, and IL-12p40), current smokers (IL-4, IL-13, IL-12p40), and women with a family history of breast or ovarian cancer (IL-4, IL-10, IL-13). Our findings suggest that risk factors for chronic diseases (age, BMI, menopausal status, parity, NSAID use, family history of breast and ovarian cancer, and smoking) are associated with inflammation markers in healthy women.
  Cytokine 12/2011; 56(3):769-78. · 3.02 Impact Factor
• Article: Variants in activators and downstream targets of ATM, radiation exposure, and contralateral breast cancer risk in the WECARE study.

  Jennifer D Brooks, Sharon N Teraoka, Anne S Reiner, Jaya M Satagopan, Leslie Bernstein, Duncan C Thomas, Marinela Capanu, Marilyn Stovall, Susan A Smith, Shan Wei, Roy E Shore, John D Boice, Charles F Lynch, Lene Mellemkjaer, Kathleen E Malone, Xiaolin Liang, Robert W Haile, Patrick Concannon, Jonine L Bernstein
  [show abstract] [hide abstract]
  ABSTRACT: Ionizing radiation (IR) is a breast carcinogen that induces DNA double-strand breaks (DSBs), and variation in genes involved in the DNA DSB response has been implicated in radiation-induced breast cancer. The Women's Environmental, Cancer, and Radiation Epidemiology (WECARE) study is a population-based study of cases with contralateral breast cancer (CBC) and matched controls with unilateral breast cancer. The location-specific radiation dose received by the contralateral breast was estimated from radiotherapy records and mathematical models. One hundred fifty-two SNPs in six genes (CHEK2, MRE11A, MDC1, NBN, RAD50, TP53BP1) involved in the DNA DSBs response were genotyped. No variants or haplotypes were associated with CBC risk (649 cases and 1,284 controls) and no variants were found to interact with radiation dose. Carriers of a RAD50 haplotype exposed to ≥1 gray (Gy) had an increased risk of CBC compared with unexposed carriers (Rate ratios [RR] = 4.31 [95% confidence intervals [CI] 1.93-9.62]); with an excess relative risk (ERR) per Gy = 2.13 [95% CI 0.61-5.33]). Although the results of this study were largely null, carriers of a haplotype in RAD50 treated with radiation had a greater CBC risk than unexposed carriers. This suggests that carriers of this haplotype may be susceptible to the DNA-damaging effects of radiation therapy associated with radiation-induced breast cancer.
  Human Mutation 09/2011; 33(1):158-64. · 5.69 Impact Factor
• Article: Body mass index and risk of second primary breast cancer: the WECARE Study.

  Jennifer D Brooks, Esther M John, Lene Mellemkjær, Anne S Reiner, Kathleen E Malone, Charles F Lynch, Jane C Figueiredo, Robert W Haile, Roy E Shore, Jonine L Bernstein, Leslie Bernstein
  [show abstract] [hide abstract]
  ABSTRACT: The identification of potentially modifiable risk factors, such as body size, could allow for interventions that could help reduce the burden of contralateral breast cancer (CBC) among breast cancer survivors. Studies examining the relationship between body mass index (BMI) and CBC have yielded mixed results. From the population-based, case-control, Women's Environmental, Cancer and Radiation Epidemiology (WECARE) Study, we included 511 women with CBC (cases) and 999 women with unilateral breast cancer (controls) who had never used postmenopausal hormone therapy. Rate ratios (RR) and 95% confidence intervals (CI) were used to assess the relationship between BMI and CBC risk. No associations between BMI at first diagnosis or weight-change between first diagnosis and date of CBC diagnosis (or corresponding date in matched controls) and CBC risk were seen. However, obese (BMI ≥ 30 kg/m(2)) postmenopausal women with estrogen receptor (ER)-negative first primary tumors (n = 12 cases and 9 controls) were at an increased risk of CBC compared with normal weight women (BMI < 25 kg/m(2)) (n = 43 cases and 98 controls) (RR = 5.64 (95% CI 1.76, 18.1)). No association between BMI and CBC risk was seen in premenopausal or postmenopausal women with ER-positive first primaries. Overall, BMI is not associated with CBC risk in this population of young breast cancer survivors. Our finding of an over five-fold higher risk of CBC in a small subgroup of obese postmenopausal women with an ER-negative first primary breast cancer is based on limited numbers and requires confirmation in a larger study.
  Breast Cancer Research and Treatment 09/2011; 131(2):571-80. · 4.43 Impact Factor
• Source

  Available from: aacrjournals.org

  Article: Circulating inflammation markers and risk of epithelial ovarian cancer.

  Tess V Clendenen, Eva Lundin, Anne Zeleniuch-Jacquotte, Karen L Koenig, Franco Berrino, Annekatrin Lukanova, Anna E Lokshin, Annika Idahl, Nina Ohlson, Goran Hallmans, Vittorio Krogh, Sabina Sieri, Paola Muti, Adele Marrangoni, Brian M Nolen, Mengling Liu, Roy E Shore, Alan A Arslan
  [show abstract] [hide abstract]
  ABSTRACT: Factors contributing to chronic inflammation appear to be associated with increased risk of ovarian cancer. The purpose of this study was to assess the association between circulating levels of inflammation mediators and subsequent risk of ovarian cancer. We conducted a case-control study of 230 cases and 432 individually matched controls nested within three prospective cohorts to evaluate the association of prediagnostic circulating levels of inflammation-related biomarkers (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p40, IL-12p70, IL-13, TNFα, IL-1Ra, sIL-1RII, sIL-2Ra, sIL-4R, sIL-6R, sTNF-R1, and sTNF-R2) measured using Luminex xMap technology with risk of ovarian cancer. We observed a trend across quartiles for IL-2 (OR(Q4 vs. Q1): 1.57, 95% CI: 0.98-2.52, P = 0.07), IL-4 (OR(Q4 vs. Q1): 1.50, 95% CI: 0.95-2.38, P = 0.06), IL-6 (OR(Q4 vs. Q1): 1.63, 95% CI: 1.03-2.58, P = 0.03), IL-12p40 (OR(Q4 vs. Q1): 1.60, 95% CI: 1.02-2.51, P = 0.06), and IL-13 (OR(Q4 vs. Q1): 1.42, 95% CI: 0.90-2.26, P = 0.11). Trends were also observed when cytokines were modeled on the continuous scale for IL-4 (P trend = 0.01), IL-6 (P trend = 0.01), IL-12p40 (P trend = 0.01), and IL-13 (P trend = 0.04). ORs were not materially different after excluding cases diagnosed less than 5 years after blood donation or when limited to serous tumors. This study provides the first direct evidence that multiple inflammation markers, specifically IL-2, IL-4, IL-6, IL-12, and IL-13, may be associated with risk of epithelial ovarian cancer, and adds to the evidence that inflammation is involved in the development of this disease.
  Cancer Epidemiology Biomarkers &amp Prevention 04/2011; 20(5):799-810. · 4.12 Impact Factor
• Article: Endogenous hormones and coronary heart disease in postmenopausal women.

  Yu Chen, Anne Zeleniuch-Jacquotte, Alan A Arslan, Oktawia Wojcik, Paolo Toniolo, Roy E Shore, Mortimer Levitz, Karen L Koenig
  [show abstract] [hide abstract]
  ABSTRACT: The association between serum levels of endogenous estrogens in postmenopausal women and the subsequent risk of coronary heart disease (CHD) was examined in a prospective case-control study nested within the New York University Women's Health Study (NYUWHS). The NYUWHS is a prospective cohort study of 14,274 healthy women enrolled between 1985 and 1991. A total of 99 women who were postmenopausal and free of cardiovascular disease at enrollment and who subsequently experienced CHD, defined as non-fatal myocardial infarction (MI), fatal CHD, percutaneous transluminal coronary angioplasty (PTCA), or coronary artery bypass grafting (CABG), were matched 1:2 by baseline age, blood sampling date, and postmenopausal status to controls who remained free of CHD as of the date of diagnosis of the matching case. Biochemical analyses for total estradiol, estrone, percent free estradiol, percent estradiol bound to sex hormone-binding globulin (SHBG), and SHBG were performed on pre-diagnostic stored serum samples. Participants had not used any hormone medications in the 6 months prior to blood collection. In the model adjusting only for matching factors, the risk of CHD in the top tertile of calculated bioavailable estradiol was elevated compared with the bottom tertile (OR=2.10; 95% CI=1.13-3.90, P for trend=0.03), and the risk in the top tertile of SHBG was reduced (OR=0.50, 95% CI=0.28-0.92, P for trend<0.01). However, these associations disappeared after adjusting for baseline hypertension status, body mass index, and serum cholesterol levels. These findings suggest that circulating estradiol and SHBG are not associated with CHD risk in postmenopausal women beyond what can be explained by the variation in hypertension status, BMI, and cholesterol.
  Atherosclerosis 02/2011; 216(2):414-9. · 3.79 Impact Factor
• Article: Thyroid cancer risk 40+ years after irradiation for an enlarged thymus: an update of the Hempelmann cohort.

  Michael Jacob Adams, Roy E Shore, Ann Dozier, Steven E Lipshultz, Ronald G Schwartz, Louis S Constine, Thomas A Pearson, Marilyn Stovall, Kelly Thevenet-Morrison, Susan G Fisher
  [show abstract] [hide abstract]
  ABSTRACT: Although ionizing radiation is a known carcinogen, the long-term risk from relatively higher-dose diagnostic procedures during childhood is less well known. We evaluated this risk indirectly by assessing thyroid cancer incidence in a cohort treated with "lower-dose" chest radiotherapy more than 55 years ago. Between 2004 and 2008, we re-surveyed a population-based cohort of subjects treated with radiation for an enlarged thymus during infancy between 1926 and 1957 and their unexposed siblings. Thyroid cancer occurred in 50 irradiated subjects (mean thyroid dose, 1.29 Gy) and in 13 nonirradiated siblings during 334,347 person-years of follow-up. After adjusting for attained age, Jewish religion, sex and history of goiter, the rate ratio for thyroid cancer was 5.6 (95% CI: 3.1-10.8). The adjusted excess relative risk per gray was 3.2 (95% CI: 1.5-6.6). The adjusted excess absolute risk per gray was 2.2 cases (95% CI: 1.4-3.2) per 10,000 person-years. Cumulative thyroid cancer incidence remains elevated in this cohort after a median 57.5 years of follow-up and is dose-dependent. Although the incidence appeared to decrease after 40 years, increased risk remains a lifelong concern in those exposed to lower doses of medical radiation during early childhood.
  Radiation Research 12/2010; 174(6):753-62. · 2.68 Impact Factor
• Article: DNA methylation in pre-diagnostic serum samples of breast cancer cases: results of a nested case-control study.

  Jennifer D Brooks, Paul Cairns, Roy E Shore, Catherine B Klein, Isaac Wirgin, Yelena Afanasyeva, Anne Zeleniuch-Jacquotte
  [show abstract] [hide abstract]
  ABSTRACT: Promoter methylation of tumor suppressor genes is a frequent and early event in breast carcinogenesis. Paired tumor tissue and serum samples from women with breast cancer show that promoter methylation is detectable in both sample types, with good concordance. This suggests the potential for these serum markers to be used for breast cancer detection. The current study was a case-control study nested within the prospective New York University Women's Health Study cohort aimed to assess the ability of promoter methylation in serum to detect pre-clinical disease. Cases were women with blood samples collected within the 6 months preceding breast cancer diagnosis (n=50). Each case was matched to 2 healthy cancer-free controls and 1 cancer-free control with a history of benign breast disease (BBD). Promoter methylation analysis of four cancer-related genes: -RASSF1A, GSTP1, APC and RARβ2, - was conducted using quantitative methylation-specific PCR. Results showed that the frequency of methylation was lower than expected among cases and higher than expected among controls. Methylation was detected in the promoter region of: RASSF1A in 22.0%, 22.9% and 17.2% of cases, BBD controls and healthy controls respectively; GSTP1 in 4%, 10.4% and 7.1% respectively; APC in 2.0%, 4.4% and 4.2% respectively and RARβ2 in 6.7%, 2.3% and 1.1% respectively. Methylation status of the four genes included in this study was unable to distinguish between cases and either control group. This study highlights some methodological issues to be addressed in planning prospective studies to evaluate methylation markers as diagnostic biomarkers.
  Cancer epidemiology. 12/2010; 34(6):717-23.
• Article: Cox regression model with time-varying coefficients in nested case-control studies.

  Mengling Liu, Wenbin Lu, Roy E Shore, Anne Zeleniuch-Jacquotte
  [show abstract] [hide abstract]
  ABSTRACT: The nested case-control (NCC) design is a cost-effective sampling method to study the relationship between a disease and its risk factors in epidemiologic studies. NCC data are commonly analyzed using Thomas' partial likelihood approach under Cox's proportional hazards model with constant covariate effects. Here, we are interested in studying the potential time-varying effects of covariates in NCC studies and propose an estimation approach based on a kernel-weighted Thomas' partial likelihood. We establish asymptotic properties of the proposed estimator, propose a numerical approach to construct simultaneous confidence bands for time-varying coefficients, and develop a hypothesis testing procedure to detect time-varying coefficients. The proposed inference procedure is evaluated in simulations and applied to an NCC study of breast cancer in the New York University Women's Health Study.
  Biostatistics 10/2010; 11(4):693-706. · 2.14 Impact Factor
• Article: Circulating cytokines and risk of B-cell non-Hodgkin lymphoma: a prospective study.

  Yian Gu, Roy E Shore, Alan A Arslan, Karen L Koenig, Mengling Liu, Sherif Ibrahim, Anna E Lokshin, Anne Zeleniuch-Jacquotte
  [show abstract] [hide abstract]
  ABSTRACT: Cytokines play important roles in B-cell activation, proliferation, and apoptosis, thus may be etiologically related to risk of B-cell non-Hodgkin lymphoma (B-NHL). However, the association between circulating levels of cytokines and B-NHL risk has not been prospectively studied in non-HIV populations. The objective of this study was to assess this association by conducting a case-control study nested within a prospective cohort of non-HIV-infected, healthy women. Fifteen cytokines were measured in samples collected a median of 8.2 years prior to diagnosis in 92 cases and two matched controls per case. Only cytokines that showed adequate temporal reproducibility over a two-year period were included. The odds ratio (OR) for the highest tertile relative to the lowest was elevated for soluble IL-2 receptor (sIL-2R) (OR = 2.5, 95% CI = 1.4-4.7, p (trend) < 0.01) and decreased for IL-13 (OR = 0.5, 95% CI = 0.2-1.0, p (trend) = 0.05). Three other cytokines were marginally associated with risk of B-NHL: TNF-alpha (OR = 1.7, 95% CI = 0.9-3.3, p (trend) = 0.11), sTNF-R2 (OR = 1.9, 95% CI = 0.9-3.5, p (trend) = 0.06), and IL-5 (OR = 0.5, 95% CI = 0.3-1.0, p (trend) = 0.06). No association was observed between B-NHL risk and levels of the other cytokines measured (IL-1beta, IL-1RA, IL-2, IL-4, IL-6, IL-10, IL-12, IL-12p70, CRP and sTNF-R1). This study suggests that dysregulated cytokines may be involved in B-NHL development.
  Cancer Causes and Control 04/2010; 21(8):1323-33. · 2.88 Impact Factor
• Article: Radiation exposure, the ATM Gene, and contralateral breast cancer in the women's environmental cancer and radiation epidemiology study.

  Jonine L Bernstein, Robert W Haile, Marilyn Stovall, John D Boice, Roy E Shore, Bryan Langholz, Duncan C Thomas, Leslie Bernstein, Charles F Lynch, Jorgen H Olsen, [......], Anne-Lise Borresen-Dale, Barry S Rosenstein, Sharon N Teraoka, Anh T Diep, Susan A Smith, Marinela Capanu, Anne S Reiner, Xiaolin Liang, Richard A Gatti, Patrick Concannon
  [show abstract] [hide abstract]
  ABSTRACT: Ionizing radiation is a known mutagen and an established breast carcinogen. The ATM gene is a key regulator of cellular responses to the DNA damage induced by ionizing radiation. We investigated whether genetic variants in ATM play a clinically significant role in radiation-induced contralateral breast cancer in women. The Women's Environmental, Cancer, and Radiation Epidemiology Study is an international population-based case-control study nested within a cohort of 52,536 survivors of unilateral breast cancer diagnosed between 1985 and 2000. The 708 case subjects were women with contralateral breast cancer, and the 1397 control subjects were women with unilateral breast cancer matched to the case subjects on age, follow-up time, registry reporting region, and race and/or ethnicity. All women were interviewed and underwent full mutation screening of the entire ATM gene. Complete medical treatment history information was collected, and for all women who received radiotherapy, the radiation dose to the contralateral breast was reconstructed using radiotherapy records and radiation measurements. Rate ratios (RRs) and corresponding 95% confidence intervals (CIs) were estimated by using multivariable conditional logistic regression. All P values are two-sided. Among women who carried a rare ATM missense variant (ie, one carried by <1% of the study participants) that was predicted to be deleterious, those who were exposed to radiation (mean radiation exposure = 1.2 Gy, SD = 0.7) had a statistically significantly higher risk of contralateral breast cancer compared with unexposed women who carried the wild-type genotype (0.01-0.99 Gy: RR = 2.8, 95% CI = 1.2 to 6.5; > or =1.0 Gy: RR = 3.3, 95% CI = 1.4 to 8.0) or compared with unexposed women who carried the same predicted deleterious missense variant (0.01-0.99 Gy: RR = 5.3, 95% CI = 1.6 to 17.3; > or =1.0 Gy: RR = 5.8, 95% CI = 1.8 to 19.0; P(trend) = .044). Women who carry rare deleterious ATM missense variants and who are treated with radiation may have an elevated risk of developing contralateral breast cancer. However, the rarity of these deleterious missense variants in human populations implies that ATM mutations could account for only a small portion of second primary breast cancers.
  CancerSpectrum Knowledge Environment 03/2010; 102(7):475-83. · 14.07 Impact Factor
• Article: Breast cancer risk 55+ years after irradiation for an enlarged thymus and its implications for early childhood medical irradiation today.

  M Jacob Adams, Ann Dozier, Roy E Shore, Steven E Lipshultz, Ronald G Schwartz, Louis S Constine, Thomas A Pearson, Marilyn Stovall, Paul Winters, Susan G Fisher
  [show abstract] [hide abstract]
  ABSTRACT: Radiotherapy during childhood increases long-term cancer risk, but the risk from radiation as a result of relatively higher dose diagnostic procedures remains less well known. This study, which evaluates breast cancer incidence in a cohort treated with "lower dose" chest radiotherapy over 50 years ago, can assist with estimating lifetime breast cancer risk in young children exposed to radiation from procedures such as chest computed tomography (CT) or treatment with recent "lower dose" chest radiotherapy protocols. A population-based, longitudinal cohort of subjects exposed to thymic irradiation during infancy from 1926 to 1957 and of their unexposed siblings was re-established. Previously followed until 1987, we resurveyed cohort members from 2004 to 2008. Poisson regression models compared breast cancer incidence rates between women in the cohort by treatment and dose category groups. Breast cancer occurred in 96 treated (mean breast dose, 0.71 Gy) and 57 untreated women during 159,459 person-years of follow-up. After adjusting for attained age and treatment/birth cohort, the rate ratio was 3.01 (2.18-4.21). The adjusted excess relative risk per Gy was 1.10 (95% confidence interval, 0.61-1.86). Traditional breast cancer risk factors did not contribute significantly to multivariate model fit. Our results show that at radiation doses between those received by the breast from chest CT and cancer therapy during early childhood, breast cancer incidence rates remain elevated >50 years after exposure. This implies that increased breast cancer risk will remain a lifelong concern in females treated during childhood with currently reduced radiotherapy doses and for infants receiving multiple chest CTs.
  Cancer Epidemiology Biomarkers &amp Prevention 01/2010; 19(1):48-58. · 4.12 Impact Factor
• Article: Circulating estrogen metabolites and risk for breast cancer in premenopausal women.

  Alan A Arslan, Roy E Shore, Yelena Afanasyeva, Karen L Koenig, Paolo Toniolo, Anne Zeleniuch-Jacquotte
  [show abstract] [hide abstract]
  ABSTRACT: It has been proposed that a shift toward 2-hydroxyestrone from 16alpha-hydroxyestrone metabolic pathway may be inversely associated with breast cancer risk because 2-hydroxyestrone is thought to be less genotoxic and estrogenic than 16alpha-hydroxyestrone. We examined the associations of invasive breast cancer risk with circulating 2-hydroxyestrone, 16alpha-hydroxyestrone, and the 2-hydroxyestrone:16alpha-hydroxyestrone ratio in a case-control study on premenopausal women nested within a prospective cohort the New York University Women's Health Study. The serum levels of 2-hydroxyestrone and 16alpha-hydroxyestrone were measured in 377 incident premenopausal breast cancer cases and 377 premenopausal controls, who were matched on age at enrollment, number and dates of blood donations, and day and phase of menstrual cycle. Overall, no significant associations were observed between breast cancer risk and serum levels of 2-hydroxyestrone, 16alpha-hydroxyestrone, or their ratio. The 2-hydroxyestrone:16alpha-hydroxyestrone ratio was positively associated with risk for estrogen receptor-positive breast cancer in the analyses controlling for matching factors. However, the association was attenuated and not significant after adjustment for potential confounders (odds ratio for the highest versus the lowest quartile, 2.15; 95% CI, 0.88-5.27; P(trend) = 0.09). The results of the current study do not support the hypothesis that a metabolic shift from 16alpha-hydroxyestrone toward 2-hydroxyestrone in premenopausal women is associated with reduced risk for breast cancer. The association between the 2-hydroxy:16alpha-hydroxyestrone ratio and estrogen receptor-positive breast cancer needs to be explored in future studies.
  Cancer Epidemiology Biomarkers &amp Prevention 09/2009; 18(8):2273-9. · 4.12 Impact Factor
• Source

  Available from: Duncan C Thomas

  Article: Statistical methods for analysis of radiation effects with tumor and dose location-specific information with application to the WECARE study of asynchronous contralateral breast cancer.

  Bryan Langholz, Duncan C Thomas, Marilyn Stovall, Susan A Smith, John D Boice, Roy E Shore, Leslie Bernstein, Charles F Lynch, Xinbo Zhang, Jonine L Bernstein
  [show abstract] [hide abstract]
  ABSTRACT: Methods for the analysis of individually matched case-control studies with location-specific radiation dose and tumor location information are described. These include likelihood methods for analyses that just use cases with precise location of tumor information and methods that also include cases with imprecise tumor location information. The theory establishes that each of these likelihood based methods estimates the same radiation rate ratio parameters, within the context of the appropriate model for location and subject level covariate effects. The underlying assumptions are characterized and the potential strengths and limitations of each method are described. The methods are illustrated and compared using the WECARE study of radiation and asynchronous contralateral breast cancer.
  Biometrics 06/2009; 65(2):599-608. · 1.83 Impact Factor
• Article: Postmenopausal levels of endogenous sex hormones and risk of colorectal cancer.

  Tess V Clendenen, Karen L Koenig, Roy E Shore, Mortimer Levitz, Alan A Arslan, Anne Zeleniuch-Jacquotte
  [show abstract] [hide abstract]
  ABSTRACT: Observational epidemiologic studies and randomized trials have reported a protective effect of oral hormonal replacement therapy on risk of colorectal cancer. Only one previous prospective study, the Women's Health Initiative Observational Study, has reported on the relationship between endogenous hormones and incident colorectal cancer. Contrary to expectation, the investigators found that women with higher circulating estradiol levels were at increased risk of developing colorectal cancer. We conducted a case-control study nested within the New York University Women's Health Study prospective cohort to evaluate the association between endogenous levels of estrone, estradiol, and sex hormone-binding globulin (SHBG) with risk of colorectal cancer. We measured hormones and SHBG in serum samples collected at enrollment from a total of 148 women who subsequently developed colorectal cancer and 293 matched controls. Circulating estrone levels were positively associated with risk of colorectal cancer: The odds ratio for the highest versus lowest quartile of estrone was 1.8 (95% confidence interval, 1.0-3.3). We found a nonsignificant inverse association between SHBG and colorectal cancer, which disappeared after adjusting for body mass index. We did not find an association between estradiol and colorectal cancer risk, but we cannot rule out a potential association because of substantial laboratory error in the measurement. Our results suggest that endogenous estrone is associated with increased risk of colorectal cancer in postmenopausal women.
  Cancer Epidemiology Biomarkers &amp Prevention 02/2009; 18(1):275-81. · 4.12 Impact Factor
• Source

  Available from: Johan Hultdin

  Article: Circulating vitamin d and risk of epithelial ovarian cancer.

  Alan A Arslan, Tess V Clendenen, Karen L Koenig, Johan Hultdin, Kerstin Enquist, Asa Agren, Annekatrin Lukanova, Hubert Sjodin, Anne Zeleniuch-Jacquotte, Roy E Shore, Göran Hallmans, Paolo Toniolo, Eva Lundin
  [show abstract] [hide abstract]
  ABSTRACT: We conducted a nested case-control study within two prospective cohorts, the New York University Women's Health Study and the Northern Sweden Health and Disease Study, to examine the association between prediagnostic circulating levels of 25-hydroxy vitamin D (25(OH)D) and the risk of subsequent invasive epithelial ovarian cancer (EOC). The 25(OH)D levels were measured in serum or plasma from 170 incident cases of EOC and 373 matched controls. Overall, circulating 25(OH)D levels were not associated with the risk of EOC in combined cohort analysis: adjusted OR for the top tertile versus the reference tertile, 1.09 (95% CI, 0.59-2.01). In addition, there was no evidence of an interaction effect between VDR SNP genotype or haplotype and circulating 25(OH)D levels in relation to ovarian cancer risk, although more complex gene-environment interactions may exist.
  Journal of Oncology 02/2009; 2009:672492.