bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from Assessing the Clinical Role of Genetic Markers of Early-Onset Prostate Cancer among High-Risk Men Enrolled in Prostate Cancer Early Detection
Authors: Hughes Lucinda , Zhu Fang , Ross Eric , Gross Laura , Uzzo Robert G. , Chen David Y.T. , Viterbo Rosalia , Rebbeck Timothy R. , Giri Veda N.
Published: April 2023

Abstract
Background: Men with familial prostate cancer and African American men are at risk for developing prostate cancer at younger ages. Genetic markers predicting early-onset prostate cancer may provide clinically useful information to guide screening strategies for high-risk men. We evaluated clinical information from six polymorphisms associated with early-onset prostate cancer in a longitudinal cohort of high-risk men enrolled in prostate cancer early detection with significant African American participation.

Methods: Eligibility criteria include ages 35 to 69 with a family history of prostate cancer or African American race. Participants undergo screening and biopsy per study criteria. Six markers associated with early-onset prostate cancer [rs2171492 (7q32), rs6983561 (8q24), rs10993994 (10q11), rs4430796 (17q12), rs1799950 (17q21), and rs266849 (19q13)] were genotyped. Cox models were used to evaluate time to prostate cancer diagnosis and prostate-specific antigen (PSA) prediction for prostate cancer by genotype. Harrell's concordance index was used to evaluate predictive accuracy for prostate cancer by PSA and genetic markers.

Results: Four hundred and sixty participants with complete data and ≥1 follow-up visit were included. Fifty-six percent were African American. Among African American men, rs6983561 genotype was significantly associated with earlier time to prostate cancer diagnosis (P = 0.005) and influenced prediction for prostate cancer by the PSA (P < 0.001). When combined with PSA, rs6983561 improved predictive accuracy for prostate cancer compared with PSA alone among African American men (PSA = 0.57 vs. PSA + rs6983561 = 0.75, P = 0.03).

Conclusions: Early-onset marker rs6983561 adds potentially useful clinical information for African American men undergoing prostate cancer risk assessment. Further study is warranted to validate these findings.

Impact: Genetic markers of early-onset prostate cancer have potential to refine and personalize prostate cancer early detection for high-risk men. Cancer Epidemiol Biomarkers Prev; 21(1); 53–60. ©2011 AACR.
Data from High Mammographic Density in Long-Term Night-Shift Workers: DDM-Spain/Var-DDM
Authors: Pedraza-Flechas Ana María , Lope Virginia , Sánchez-Contador Carmen , Santamariña Carmen , Pedraz-Pingarrón Carmen , Moreo Pilar , Ederra María , Miranda-García Josefa , Vidal Carmen , Llobet Rafael , Aragonés Nuria , Salas-Trejo Dolores , Pollán Marina , Pérez-Gómez Beatriz
Published: April 2023

Abstract
Background: Night-shift work (NSW) has been suggested as a possible cause of breast cancer, and its association with mammographic density (MD), one of the strongest risk factors for breast cancer, has been scarcely addressed. This study examined NSW and MD in Spanish women.

Methods: The study covered 2,752 women aged 45–68 years recruited in 2007–2008 in 7 population-based public breast cancer screening centers, which included 243 women who had performed NSW for at least one year. Occupational data and information on potential confounders were collected by personal interview. Two trained radiologist estimated the percentage of MD assisted by a validated semiautomatic computer tool (DM-scan). Multivariable mixed linear regression models with random screening center–specific intercepts were fitted using log-transformed percentage of MD as the dependent variable and adjusting by known confounding variables.

Results: Having ever worked in NSW was not associated with MD [{e^\beta }$:0.96; 95% confidence interval (CI), 0.86–1.06]. However, the adjusted geometric mean of the percentage of MD in women with NSW for more than 15 years was 25% higher than that of those without NSW history (MD>15 years:20.7% vs. MDnever:16.5%;{e^\beta }$:1.25; 95% CI,1.01–1.54). This association was mainly observed in postmenopausal participants ({e^\beta }$:1.28; 95% CI, 1.00–1.64). Among NSW-exposed women, those with ≤2 night-shifts per week had higher MD than those with 5 to 7 nightshifts per week ({e^\beta }$:1.42; 95% CI, 1.10–1.84).

Conclusions: Performing NSW was associated with higher MD only in women with more than 15 years of cumulated exposure. These findings warrant replication in futures studies.

Impact: Our findings suggest that MD could play a role in the pathway between long-term NSW and breast cancer. Cancer Epidemiol Biomarkers Prev; 26(6); 905–13. ©2017 AACR.
Data from Urinary Metabolite Risk Biomarkers of Lung Cancer: A Prospective Cohort Study
Authors: Haznadar Majda , Cai Qiuyin , Krausz Kristopher W. , Bowman Elise D. , Margono Ezra , Noro Rintaro , Thompson Matthew D. , Mathé Ewy A. , Munro Heather M. , Steinwandel Mark D. , Gonzalez Frank J. , Blot William J. , Harris Curtis C.
Published: April 2023

Abstract
Background: Lung cancer is a major health burden causing 160,000 and 1.6 million deaths annually in the United States and worldwide, respectively.

Methods: While seeking to identify stable and reproducible biomarkers in noninvasively collected biofluids, we assessed whether previously identified metabolite urinary lung cancer biomarkers, creatine riboside (CR), N-acetylneuraminic acid (NANA), cortisol sulfate, and indeterminate metabolite 561+, were elevated in the urines of subjects prior to lung cancer diagnosis in a well-characterized prospective Southern Community Cohort Study (SCCS). Urine was examined from 178 patients and 351 nondiseased controls, confirming that one of four metabolites was associated with lung cancer risk in the overall case–control set, whereas two metabolites were associated with lung cancer risk in European-Americans.

Results: OR of lung cancer associated with elevated CR levels, and adjusted for smoking and other potential confounders, was 2.0 [95% confidence interval (CI), 1.2–3.4; P= 0.01]. In European-Americans, both CR and NANA were significantly associated with lung cancer risk (OR = 5.3; 95% CI, 1.6–17.6; P= 0.006 and OR=3.5; 95% CI, 1.5–8.4; P= 0.004, respectively). However, race itself did not significantly modify the associations. ROC analysis showed that adding CR and NANA to a model containing previously established lung cancer risk factors led to a significantly improved classifier (P= 0.01). Increasing urinary levels of CR and NANA displayed a positive association with increasing tumor size, strengthening a previously established link to altered tumor metabolism.

Conclusion and Impact: These replicated results provide evidence that identified urinary metabolite biomarkers have a potential utility as noninvasive, clinical screening tools for early diagnosis of lung cancer. Cancer Epidemiol Biomarkers Prev; 25(6); 978–86. ©2016 AACR.
Data from Germline Genetic Variants and Lung Cancer Survival in African Americans
Authors: Jones Carissa C. , Bush William S. , Crawford Dana C. , Wenzlaff Angela S. , Schwartz Ann G. , Wiencke John K. , Wrensch Margaret R. , Blot William J. , Chanock Stephen J. , Grogan Eric L. , Aldrich Melinda C.
Published: April 2023

Abstract
Background: African Americans have the highest lung cancer mortality in the United States. Genome-wide association studies (GWASs) of germline variants influencing lung cancer survival have not yet been conducted with African Americans. We examined five previously reported GWAS catalog variants and explored additional genome-wide associations among African American lung cancer cases.

Methods: Incident non–small cell lung cancer cases (N = 286) in the Southern Community Cohort Study were genotyped on the Illumina HumanExome BeadChip. We used Cox proportional hazards models to estimate HRs and 95% confidence intervals (CIs) for overall mortality. Two independent African American studies (N = 316 and 298) were used for replication.

Results: One previously reported variant, rs1878022 on 12q23.3, was significantly associated with mortality (HR = 0.70; 95% CI: 0.54–0.92). Replication findings were in the same direction, although attenuated (HR = 0.87 and 0.94). Meta-analysis had a HR of 0.83 (95% CI, 0.71–0.97). Analysis of common variants identified an association between chromosome 6q21.33 and mortality (HR = 0.46; 95% CI, 0.33–0.66).

Conclusions: We identified an association between rs1878022 in CMKLR1 and lung cancer survival. However, our results in African Americans have a different direction of effect compared with a prior study in European Americans, suggesting a different genetic architecture or presence of gene–environment interactions. We also identified variants on chromosome 6 within the gene-rich HLA region, which has been previously implicated in lung cancer risk and survival.

Impact: We found evidence that inherited genetic risk factors influence lung cancer survival in African Americans. Replication in additional populations is necessary to confirm potential genetic differences in lung cancer survival across populations. Cancer Epidemiol Biomarkers Prev; 26(8); 1288–95. ©2017 AACR.
Data from Alcohol Consumption in Relation to Plasma Sex Hormones, Prolactin, and Sex Hormone–Binding Globulin in Premenopausal Women
Authors: Hirko Kelly A. , Spiegelman Donna , Willett Walter C. , Hankinson Susan E. , Eliassen A. Heather
Published: April 2023

Abstract
Background: Alcohol consumption is a consistent risk factor for breast cancer, and evidence suggests premenopausal plasma hormones are associated with breast cancer.

Methods: Plasma concentrations of estradiol, estrone, estrone sulfate, testosterone, androstenedione, progesterone, prolactin, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), and sex hormone–binding globulin (SHBG) were measured in samples collected in 1996–99. Average alcohol intake was calculated from semiquantitative food frequency questionnaires collected in 1995 and 1999. We used generalized linear models to calculate geometric mean hormone concentrations across alcohol categories and the percentage difference for the highest versus lowest category.

Results: Comparing women who consumed >20 g/d with nondrinkers, levels were 25.7% higher for luteal estrone (geometric mean, 106 vs. 84.5 pg/mL; Ptrend = 0.001), 27.2% higher for luteal estradiol (182 vs. 143 pg/mL; Ptrend = 0.006), and 16.8% higher for SHBG (85.6 vs. 73.3 nmol/L; Ptrend = 0.03); concentrations of free testosterone were 17.9% lower (0.16 vs. 0.20 ng/dL; Ptrend = 0.002). Women consuming >10 g/d compared with nondrinkers had 26.5% higher concentrations of follicular estrone sulfate (950 vs. 751 pg/mL; Ptrend = 0.04). We did not observe significant associations between alcohol and the other sex hormones evaluated. Significant positive associations were observed with beer intake, but not other alcohol types, for DHEA (Pinteraction = 0.003) and androstenedione (Pinteraction = 0.006).

Conclusion: Alcohol consumption was significantly positively associated with plasma luteal estrogen concentrations, but not with androgen levels, nor estrone or estradiol measured in the follicular phase.

Impact: Differences in premenopausal estrogen levels may contribute to the association between alcohol and breast cancer. Cancer Epidemiol Biomarkers Prev; 23(12); 2943–53. ©2014 AACR.
Data from Markers of Vitamin D Exposure and Esophageal Cancer Risk: A Systematic Review and Meta-analysis
Authors: Zgaga Lina , O'Sullivan Fiona , Cantwell Marie M. , Murray Liam J. , Thota Prashanthi N. , Coleman Helen G.
Published: April 2023

Abstract
Vitamin D has been associated with reduced risk of many cancers, but evidence for esophageal cancer is mixed. To clarify the role of vitamin D, we performed a systematic review and meta-analysis to evaluate the association of vitamin D exposures and esophageal neoplasia, including adenocarcinoma, squamous cell carcinoma (SCC), Barrett's esophagus, and squamous dysplasia. Ovid MEDLINE, EMBASE, and Web of Science were searched from inception to September 2015. Fifteen publications in relation to circulating 25-hydroxyvitamin D [25(OH)D; n = 3], vitamin D intake (n = 4), UVB exposure (n = 1), and genetic factors (n = 7) were retrieved. Higher [25(OH)D] was associated with increased risk of cancer [adenocarcinoma or SCC, OR = 1.39; 95% confidence interval (CI), 1.04–1.74], with the majority of participants coming from China. No association was observed between vitamin D intake and risk of cancer overall (OR, 1.03; 0.65–1.42); however, a nonsignificantly increased risk for adenocarcinoma (OR, 1.45; 0.65–2.24) and nonsignificantly decreased risk for SCC (OR, 0.80; 0.48–1.12) were observed. One study reported a decreased risk of adenocarcinoma with higher UVB exposure. A decreased risk was found for VDR haplotype rs2238135(G)/rs1989969(T) carriers (OR, 0.45; 0.00–0.91), and a suggestive association was observed for rs2107301. In conclusion, no consistent associations were observed between vitamin D exposures and occurrence of esophageal lesions. Further adequately powered, well-designed studies are needed before conclusions can be made. Cancer Epidemiol Biomarkers Prev; 25(6); 877–86. ©2016 AACR.
Data from Germline Variation in Apoptosis Pathway Genes and Risk of Non–Hodgkin's Lymphoma
Authors: Kelly Jennifer L. , Novak Anne J. , Fredericksen Zachary S. , Liebow Mark , Ansell Stephen M. , Dogan Ahmet , Wang Alice H. , Witzig Thomas E. , Call Timothy G. , Kay Neil E. , Habermann Thomas M. , Slager Susan L. , Cerhan James R.
Published: April 2023

Abstract
Background: The t(14;18)(q32;q21) translocation is the most commonly observed chromosomal translocation in non–Hodgkin's lymphoma (NHL), resulting in constitutive Bcl-2 expression and apoptosis inhibition. In addition, germline variation in both BCL2L11 (BIM) and CASP9, known regulators of apoptosis, has recently been linked to NHL risk. We conducted a comprehensive evaluation of 36 apoptosis pathway genes with risk of NHL.

Methods: We genotyped 226 single-nucleotide polymorphisms (SNP) from 36 candidate genes in a clinic-based study of 441 newly diagnosed NHL cases and 475 frequency-matched controls. We used principal components analysis to assess gene-level associations, and logistic regression to assess SNP-level associations. MACH was used for imputation of SNPs in BCL2L11 and CASP9.

Results: In gene-level analyses, BCL2L11 (P = 0.0019), BCLAF1 (P = 0.0097), BAG5 (P = 0.026), and CASP9 (P = 0.0022) were associated with NHL risk after accounting for multiple testing (tail strength, 0.38; 95% confidence interval, 0.05-0.70). Two of the five BCL2L11 tagSNPs (rs6746608 and rs12613243), both genotyped BCLAF1 tagSNPs (rs797558 and rs703193), the single genotyped BAG5 tagSNP (rs7693), and three of the seven genotyped CASP9 tagSNPs (rs6685648, rs2020902, and rs2042370) were significant at P < 0.05. We successfully imputed BCL2L11 and CASP9 SNPs previously linked to NHL, and replicated all four BCL2L11 and two of three CASP9 SNPs.

Conclusion: We replicated the association of BCL2L11 and CASP9 with NHL risk at the gene and SNP level, and identified novel associations with BCLAF1 and BAG5.

Impact: Closer evaluation of germline variation of genes in the apoptosis pathway with risk of NHL and its subtypes is warranted. Cancer Epidemiol Biomarkers Prev; 19(11); 2847–58. ©2010 AACR.
Data from Circulating Sex Hormones and Terminal Duct Lobular Unit Involution of the Normal Breast
Authors: Khodr Zeina G. , Sherman Mark E. , Pfeiffer Ruth M. , Gierach Gretchen L. , Brinton Louise A. , Falk Roni T. , Patel Deesha A. , Linville Laura M. , Papathomas Daphne , Clare Susan E. , Visscher Daniel W. , Mies Carolyn , Hewitt Stephen M. , Storniolo Anna Maria V. , Rosebrock Adrian , Caban Jesus J. , Figueroa Jonine D.
Published: April 2023

Abstract
Background: Terminal duct lobular units (TDLU) are the predominant source of breast cancers. Lesser degrees of age-related TDLU involution have been associated with increased breast cancer risk, but factors that influence involution are largely unknown. We assessed whether circulating hormones, implicated in breast cancer risk, are associated with levels of TDLU involution using data from the Susan G. Komen Tissue Bank (KTB) at the Indiana University Simon Cancer Center (2009–2011).

Methods: We evaluated three highly reproducible measures of TDLU involution, using normal breast tissue samples from the KTB (n = 390): TDLU counts, median TDLU span, and median acini counts per TDLU. RRs (for continuous measures), ORs (for categorical measures), 95% confidence intervals (95% CI), and Ptrends were calculated to assess the association between tertiles of estradiol, testosterone, sex hormone–binding globulin (SHBG), progesterone, and prolactin with TDLU measures. All models were stratified by menopausal status and adjusted for confounders.

Results: Among premenopausal women, higher prolactin levels were associated with higher TDLU counts (RRT3vsT1:1.18; 95% CI: 1.07–1.31; Ptrend = 0.0005), but higher progesterone was associated with lower TDLU counts (RRT3vsT1: 0.80; 95% CI: 0.72–0.89; Ptrend < 0.0001). Among postmenopausal women, higher levels of estradiol (RRT3vsT1:1.61; 95% CI: 1.32–1.97; Ptrend < 0.0001) and testosterone (RRT3vsT1: 1.32; 95% CI: 1.09–1.59; Ptrend = 0.0043) were associated with higher TDLU counts.

Conclusions: These data suggest that select hormones may influence breast cancer risk potentially through delaying TDLU involution.

Impact: Increased understanding of the relationship between circulating markers and TDLU involution may offer new insights into breast carcinogenesis. Cancer Epidemiol Biomarkers Prev; 23(12); 2765–73. ©2014 AACR.
Data from Variation in Levels of the Lung Carcinogen NNAL and Its Glucuronides in the Urine of Cigarette Smokers from Five Ethnic Groups with Differing Risks for Lung Cancer
Authors: Park Sungshim L. , Carmella Steven G. , Ming Xun , Vielguth Elizabeth , Stram Daniel O. , Le Marchand Loic , Hecht Stephen S.
Published: April 2023

Abstract
Background: Results of the Multiethnic Cohort (MEC) study demonstrated that, for the same quantity of cigarettes smoked, African Americans and Native Hawaiians have a higher risk of lung cancer compared with whites, whereas Latinos and Japanese Americans have a lower risk. We hypothesize that the uptake and/or metabolism of the lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) could explain the differences in lung cancer risk.

Methods: We measured urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronides and their sum (total NNAL), biomarkers of NNK uptake, in 2,252 smokers from the MEC. Ethnic-specific geometric means were compared adjusting for age at urine collection, sex, creatinine and total nicotine equivalents, a marker of total nicotine uptake.

Results: African Americans had the highest median total NNAL levels (1.80 pmol/mL urine) and Japanese Americans had the lowest (0.914 pmol/mL urine), with intermediate values in the other three groups. Geometric mean of total NNAL in African Americans was also highest, and in Japanese Americans it was lowest; Japanese American geometric mean was statistically different from whites (P = 0.004).

Conclusions: African Americans had higher levels of total NNAL per mL urine than whites, while Japanese Americans had lower levels, consistent with lung cancer risk among smokers in these groups. However, our data were not consistent with the high and low lung cancer risks of Native Hawaiian and Latino smokers, respectively.

Impact: The higher lung cancer susceptibility of African-American smokers and the lower susceptibility of Japanese-American smokers compared with whites can be explained in part by exposure to the potent lung carcinogen NNK. Cancer Epidemiol Biomarkers Prev; 24(3); 561–9. ©2014 AACR.
Data from Nut Consumption and Lung Cancer Risk: Results from Two Large Observational Studies
Authors: Lee Jennifer T. , Lai Gabriel Y. , Liao Linda M. , Subar Amy F. , Bertazzi Pier Alberto , Pesatori Angela C. , Freedman Neal D. , Landi Maria Teresa , Lam Tram Kim
Published: April 2023

Abstract
Background: Epidemiologic evidence on the association between nut consumption and lung cancer risk is limited.

Methods: We investigated this relationship in the Environment and Genetics in Lung Cancer Etiology (EAGLE) study, a population-based case–control study, and the National Institutes of Health (NIH) American Association of Retired Persons (AARP) Diet and Health Study, a prospective cohort. We identified 2,098 lung cases for EAGLE and 18,533 incident cases in AARP. Diet was assessed by food frequency questionnaire for both studies. Multivariable ORs and HRs and respective 95% confidence intervals (CI) were calculated using unconditional logistic regression and Cox proportional hazards regression for EAGLE and AARP, respectively.

Results: Higher frequency of intake of nut consumption was inversely associated with overall lung cancer risk (highest vs. lowest quintile, OREAGLE = 0.74; 95% CI, 0.57–0.95; HRAARP = 0.86; 95% CI, 0.81–0.91), regardless of smoking status. Results from the prospective cohort showed similar associations across histologic subtypes and a more pronounced benefits from nut consumption for those who smoked 1 to 20 cigarettes/day (OREAGLE = 0.61; 95% CI, 0.39–0.95; HRAARP = 0.83; 95% CI, 0.74–0.94).

Conclusions: Nut consumption was inversely associated with lung cancer in two large population-based studies, and associations were independent of cigarette smoking and other known risk factors.

Impact: To our knowledge, this is the first study that examined the association between nut consumption and lung cancer risk by histologic subtypes and smoking intensity. Cancer Epidemiol Biomarkers Prev; 26(6); 826–36. ©2017 AACR.
Data from Association of Mitotic Regulation Pathway Polymorphisms with Pancreatic Cancer Risk and Outcome
Authors: Couch Fergus J. , Wang Xianshu , Bamlet William R. , de Andrade Mariza , Petersen Gloria M. , McWilliams Robert R.
Published: April 2023

Abstract
Background: Mitosis is a highly regulated process that serves to ensure the fidelity of cell division. The disruption of mitotic regulators leading to aneuploidy and polyploidy is commonly observed in cancer cells. Single nucleotide polymorphisms (SNP) in regulators of mitosis may promote chromosome missegregation and influence pancreatic cancer and/or survival.

Methods: Thirty-four SNPs, previously associated with breast cancer risk, from 33 genes involved in the regulation of mitosis, were investigated for associations with pancreatic cancer risk in 1,143 Caucasian patients with pancreatic adenocarcinoma and 1,097 unaffected controls from the Mayo Clinic. Associations with survival from pancreatic cancer were also assessed using 1,030 pancreatic cancer cases with known outcome.

Results: Two SNPs in the APC (rs2431238) and NIN (rs10145182) loci, of 34 examined, were significantly associated with pancreatic cancer risk (P = 0.035 and P = 0.038, respectively). Further analyses of individuals categorized by smoking and body mass index identified several SNPs displaying significant associations (P < 0.05) with pancreatic cancer risk, including APC rs2431238 in individuals with high body mass index (≥30; P = 0.031) and NIN rs10145182 in ever smokers (P = 0.01). In addition, survival analyses detected significant associations between SNPs in EIF3S10 and overall survival (P = 0.009), SNPs from five genes and survival in resected cancer cases (P < 0.05), and SNPs from two other genes (P < 0.05) and survival of locally advanced cancer cases.

Conclusion: Common variation in genes encoding regulators of mitosis may independently influence pancreatic cancer susceptibility and survival. Cancer Epidemiol Biomarkers Prev; 19(1); 251–7
Data from Benzene Uptake in Hookah Smokers and Non-smokers Attending Hookah Social Events: Regulatory Implications
Authors: Kassem Nada O.F. , Kassem Noura O. , Jackson Sheila R. , Liles Sandy , Daffa Reem M. , Zarth Adam T. , Younis Maram A. , Carmella Steven G. , Hofstetter C. Richard , Chatfield Dale A. , Matt Georg E. , Hecht Stephen S. , Hovell Melbourne F.
Published: April 2023

Abstract
Background: Benzene is a human hematotoxicant and a leukemogen that causes lymphohematopoietic cancers, especially acute myelogenous leukemia. We investigated uptake of benzene in hookah smokers and non-smokers attending hookah social events in naturalistic settings where hookah tobacco was smoked exclusively.

Methods: We quantified S-phenylmercapturic acid (SPMA), a metabolite of benzene, in the urine of 105 hookah smokers and 103 non-smokers. Participants provided spot urine samples the morning of and the morning after attending an indoor hookah-only smoking social event at a hookah lounge or in a private home.

Results: Urinary SPMA levels in hookah smokers increased significantly following a hookah social event (P < 0.001). This increase was 4.2 times higher after hookah lounge events (P < 0.001) and 1.9 times higher after home events (P = 0.003). In non-smokers, urinary SPMA levels increased 2.6 times after hookah lounge events (P = 0.055); however, similar urinary SPMA levels were detected before and after home events, possibly indicating chronic exposure to benzene (P = 0.933).

Conclusions: Our data provide the first evidence for uptake of benzene in hookah smokers and non-smokers exposed to hookah tobacco secondhand smoke at social events in private homes compared with their counterparts in hookah lounges. Hookah tobacco smoke is a source of benzene exposure, a risk factor for leukemia.

Impact: Because there is no safe level of exposure to benzene, our results call for interventions to reduce or prevent hookah tobacco use, regulatory actions to limit hookah-related exposure to toxicants including benzene, initiate labeling of hookah-related products, and include hookah smoking in clean indoor air legislation. Cancer Epidemiol Biomarkers Prev; 23(12); 2793–809. ©2014 AACR.
Data from Cancer Risk in Women Treated with Fertility Drugs According to Parity Status—A Registry-based Cohort Study
Authors: Reigstad Marte Myhre , Storeng Ritsa , Myklebust Tor Åge , Oldereid Nan Birgitte , Omland Anne Katerine , Robsahm Trude Eid , Brinton Louise Annette , Vangen Siri , Furu Kari , Larsen Inger Kristin
Published: April 2023

Abstract
Background: Long-term safety of assisted reproductive techniques (ART) is of interest as their use is increasing. Cancer risk is known to be affected by parity. This study examined the risk of cancer after fertility treatment, stratified by women's parity.

Methods: Data were obtained from all women (n = 1,353,724) born in Norway between 1960 and 1996. Drug exposure data (2004–2014) were obtained from the Norwegian Prescription Database (drugs used in ART and clomiphene citrate). The Medical Birth Registry of Norway provided parity status. HRs were calculated for all site cancer, breast, cervical, endometrial, ovarian, colorectal, central nervous system, thyroid cancer, and malignant melanoma.

Results: In 12,354,392 person-years of follow-up, 20,128 women were diagnosed with cancer. All-site cancer risk was 1.14 [95% confidence interval (95% CI), 1.03–1.26] and 1.10 (95% CI, 0.98–1.23) after clomiphene citrate and ART exposure, respectively. For ovarian cancer, a stronger association was observed for both exposures in nulliparous (HR, 2.49; 95% CI, 1.30–4.78; and HR, 1.62; 95% CI, 0.78–3.35) versus parous women (HR, 1.37; 95% CI, 0.64–2.96; and HR, 0.87; 95% CI, 0.33–2.27). Elevated risk of endometrial cancers was observed for clomiphene citrate exposure in nulliparous women (HR, 4.49; 95% CI, 2.66–7.60 vs. HR, 1.52; 95% CI, 0.67–3.42). Risk was elevated for breast cancer in parous women exposed to clomiphene citrate (HR, 1.26; 95% CI, 1.03–1.54) for thyroid cancer and among nulliparous women after ART treatment (HR, 2.19; 95% CI, 1.08–4.44).

Conclusions: Clomiphene citrate appears associated with increased risk of ovarian and endometrial cancer. Elevations in risks of breast and thyroid cancer were less consistent across type of drug exposure and parity.

Impact: Continued monitoring of fertility treatments is warranted. Cancer Epidemiol Biomarkers Prev; 26(6); 953–62. ©2017 AACR.
Data from Tobacco and Alcohol in Relation to Male Breast Cancer: An Analysis of the Male Breast Cancer Pooling Project Consortium
Authors: Cook Michael B. , Guénel Pascal , Gapstur Susan M. , van den Brandt Piet A. , Michels Karin B. , Casagrande John T. , Cooke Rosie , Van Den Eeden Stephen K. , Ewertz Marianne , Falk Roni T. , Gaudet Mia M. , Gkiokas George , Habel Laurel A. , Hsing Ann W. , Johnson Kenneth , Kolonel Laurence N. , La Vecchia Carlo , Lynge Elsebeth , Lubin Jay H. , McCormack Valerie A. , Negri Eva , Olsson Håkan , Parisi Dominick , Petridou Eleni Th. , Riboli Elio , Sesso Howard D. , Swerdlow Anthony , Thomas David B. , Willett Walter C. , Brinton Louise A.
Published: April 2023

Abstract
Background: The etiology of male breast cancer is poorly understood, partly due to its relative rarity. Although tobacco and alcohol exposures are known carcinogens, their association with male breast cancer risk remains ill-defined.

Methods: The Male Breast Cancer Pooling Project consortium provided 2,378 cases and 51,959 controls for analysis from 10 case–control and 10 cohort studies. Individual participant data were harmonized and pooled. Unconditional logistic regression was used to estimate study design–specific (case–control/cohort) ORs and 95% confidence intervals (CI), which were then combined using fixed-effects meta-analysis.

Results: Cigarette smoking status, smoking pack-years, duration, intensity, and age at initiation were not associated with male breast cancer risk. Relations with cigar and pipe smoking, tobacco chewing, and snuff use were also null. Recent alcohol consumption and average grams of alcohol consumed per day were also not associated with risk; only one subanalysis of very high recent alcohol consumption (>60 g/day) was tentatively associated with male breast cancer (ORunexposed referent = 1.29; 95% CI, 0.97–1.71; OR>0–<7 g/day referent = 1.36; 95% CI, 1.04–1.77). Specific alcoholic beverage types were not associated with male breast cancer. Relations were not altered when stratified by age or body mass index.

Conclusions: In this analysis of the Male Breast Cancer Pooling Project, we found little evidence that tobacco and alcohol exposures were associated with risk of male breast cancer.

Impact: Tobacco and alcohol do not appear to be carcinogenic for male breast cancer. Future studies should aim to assess these exposures in relation to subtypes of male breast cancer. Cancer Epidemiol Biomarkers Prev; 24(3); 520–31. ©2014 AACR.
Data from Common Variation in Nemo-Like Kinase Is Associated with Risk of Ovarian Cancer
Authors: Stevens Kristen N. , Kelemen Linda E. , Wang Xianshu , Fridley Brooke L. , Vierkant Robert A. , Fredericksen Zachary , Armasu Sebastian M. , Tsai Ya-Yu , Berchuck Andrew , Narod Steven A. , Phelan Catherine M. , Sutphen Rebecca , Birrer Michael J. , Schildkraut Joellen M. , Sellers Thomas A. , Goode Ellen L. , Couch Fergus J.
Published: April 2023

Abstract
Background: Overexpression of mitotic kinases has been associated with prognosis, histologic grade, and clinical stage in ovarian cancer, but the relationship between inherited variation in these genes and ovarian cancer risk has not been well defined.

Methods: We measured associations between 397 single nucleotide polymorphisms (SNPs) from 67 mitotic kinases and invasive epithelial ovarian cancer risk in two case–control studies (n = 671 cases; n = 939 controls). Thirty-six candidate SNPs (P < 0.05) were assessed in a replication analysis consisting of three additional studies (n = 1,094 cases; n = 829 controls).

Results: In initial analysis, thirty-six SNPs were suggestive of association with risk of serous ovarian cancer, all subtypes of ovarian cancer, or both (P < 0.05). Replication analyses suggested an association between rs2125846 in the Nemo-like kinase (NLK) gene and ovarian cancer (serous OR = 1.36, 95% CI: 1.11–1.67, P = 1.77 × 10−3; all subtypes OR = 1.30, 95% CI: 1.08–1.56, P = 2.97 × 10−3). Furthermore, rs2125846 was associated with risk in the combined discovery and replication sets (serous OR = 1.33, 95% CI: 1.15–1.54; all subtypes OR = 1.27, 95% CI: 1.12–1.45).

Conclusions: Variation in NLK may be associated with risk of invasive epithelial ovarian cancer. Further studies are needed to confirm and understand the biologic relationship between this mitotic kinase and ovarian cancer risk.

Impact: An association between SNPs in NLK and ovarian cancer may provide biologic insight into the development of this disease. Cancer Epidemiol Biomarkers Prev; 21(3); 523–8. ©2012 AACR.
Data from A Population-Based Study of Sociodemographic and Geographic Variation in HPV Vaccination
Authors: Finney Rutten Lila J. , Wilson Patrick M. , Jacobson Debra J. , Agunwamba Amenah A. , Radecki Breitkopf Carmen , Jacobson Robert M. , St. Sauver Jennifer L.
Published: April 2023

Abstract
Background: Human papillomavirus (HPV) vaccination rates in the United States remain low and lag behind other recommended adolescent vaccines. Studies evaluating the association of geographic and area-level characteristics with HPV vaccination rates provide a valuable resource for public health planning.

Method: We used the Rochester Epidemiology Project data linkage system to ascertain HPV vaccination rates between 2010 and 2015 in a 7-county region of southern Minnesota. Geocoded individual patient data were spatially linked to socioeconomic data from the American Community Survey at the census block group level. Bayesian hierarchical logistic regression was used to model incident vaccination rates, adjusting for individual- and area-level sociodemographic characteristics, and geolocation. Geolocation was modeled as an approximated Gaussian field using a Stochastic Partial Differential Equations approach. All models were estimated using Integrated Nested Laplace Approximations.

Results: In adjusted models, increasing age and female sex were associated with increased HPV vaccination. Lower socioeconomic status was associated with decreased rates of initiation [adjusted odds ratio (AOR); 95% confidence interval = 0.90 (0.86–0.95)], completion of the second dose [AOR = 0.88 (0.83–0.93)], and completion of the third dose [AOR = 0.85 (0.80–0.92)]. Geographic spatial analysis demonstrated increased odds of vaccination for the eastern region and in the greater Rochester metropolitan area, showing significant spatial variation not explained by individual level characteristics and ACS block group-level data.

Conclusions: HPV vaccination rates varied geographically and by individual and geographically indexed sociodemographic characteristics.

Impact: Identifying geographic regions with low HPV vaccination rates can help target clinical and community efforts to improve vaccination rates. Cancer Epidemiol Biomarkers Prev; 26(4); 533–40. ©2017 AACR.

See all the articles in this CEBP Focus section, “Geospatial Approaches to Cancer Control and Population Sciences.”
Data from Association between Vitamin D Deficiency and Antinuclear Antibodies in Middle-Aged and Older U.S. Adults
Authors: Meier Helen C.S. , Sandler Dale P. , Simonsick Eleanor M. , Parks Christine G.
Published: April 2023

Abstract
Background: Vitamin D deficiency is associated with cancer and autoimmune diseases, but little is known about the association between vitamin D and antinuclear antibodies (ANA), a biomarker of immune dysfunction in healthy populations. The objective of this study was to determine whether vitamin D deficiency is associated with ANA in middle-aged and older U.S. adults.

Methods: A cross-sectional analysis using the National Health and Nutrition Examination Survey (NHANES) 2001–2004 was conducted. Data were available for 1,012 adults aged 50 years and older. Serum 25-hydroxyvitamin D levels were measured by radioimmunoassay. ANA was measured in a 1:80 dilution of sera by immunofluorescence using HEp-2 cells (seropositive = 3 or 4+).

Results: Greater vitamin D deficiency was associated with higher ANA prevalence in the unadjusted (Ptrend = 0.0002) logistic regression model and after adjustment for sex, age, education, race/ethnicity, season, and NHANES cycle (Ptrend = 0.04). After adjustment, those with severe vitamin D deficiency (<10 ng/mL) had 2.99 (95% CI, 1.25–7.15) times the odds of ANA compared with having normal vitamin D levels (≥30 ng/mL), while deficient and insufficient individuals had twice the odds of ANA.

Conclusions: Among U.S. residents ages 50 and older, vitamin D deficiency was associated with higher prevalence of ANA. Vitamin D sufficiency may be important for preventing immune dysfunction in older populations.

Impact: Our findings support the growing evidence that vitamin D is an important immune modulator. Vitamin D deficiency in older adults may increase vulnerability to cancer by contributing to immune dysfunction. Cancer Epidemiol Biomarkers Prev; 25(12); 1559–63. ©2016 AACR.
Data from Contextual Correlates of Physical Activity among Older Adults: A Neighborhood Environment-Wide Association Study (NE-WAS)
Authors: Mooney Stephen J. , Joshi Spruha , Cerdá Magdalena , Kennedy Gary J. , Beard John R. , Rundle Andrew G.
Published: April 2023

Abstract
Background: Few older adults achieve recommended physical activity levels. We conducted a “neighborhood environment-wide association study (NE-WAS)” of neighborhood influences on physical activity among older adults, analogous, in a genetic context, to a genome-wide association study.

Methods: Physical Activity Scale for the Elderly (PASE) and sociodemographic data were collected via telephone survey of 3,497 residents of New York City aged 65 to 75 years. Using Geographic Information Systems, we created 337 variables describing each participant's residential neighborhood's built, social, and economic context. We used survey-weighted regression models adjusting for individual-level covariates to test for associations between each neighborhood variable and (i) total PASE score, (ii) gardening activity, (iii) walking, and (iv) housework (as a negative control). We also applied two “Big Data” analytic techniques, LASSO regression, and Random Forests, to algorithmically select neighborhood variables predictive of these four physical activity measures.

Results: Of all 337 measures, proportion of residents living in extreme poverty was most strongly associated with total physical activity [−0.85; (95% confidence interval, −1.14 to −0.56) PASE units per 1% increase in proportion of residents living with household incomes less than half the federal poverty line]. Only neighborhood socioeconomic status and disorder measures were associated with total activity and gardening, whereas a broader range of measures was associated with walking. As expected, no neighborhood meaZsures were associated with housework after accounting for multiple comparisons.

Conclusions: This systematic approach revealed patterns in the domains of neighborhood measures associated with physical activity.

Impact: The NE-WAS approach appears to be a promising exploratory technique. Cancer Epidemiol Biomarkers Prev; 26(4); 495–504. ©2017 AACR.

See all the articles in this CEBP Focus section, “Geospatial Approaches to Cancer Control and Population Sciences.”
Data from UGT1A and UGT2B Genetic Variation Alters Nicotine and Nitrosamine Glucuronidation in European and African American Smokers
Authors: Wassenaar Catherine A. , Conti David V. , Das Soma , Chen Peixian , Cook Edwin H. , Ratain Mark J. , Benowitz Neal L. , Tyndale Rachel F.
Published: April 2023

Abstract
Background: Identifying sources of variation in the nicotine and nitrosamine metabolic inactivation pathways is important to understanding the relationship between smoking and cancer risk. Numerous UGT1A and UGT2B enzymes are implicated in nicotine and nitrosamine metabolism in vitro; however, little is known about their roles in vivo.

Methods: Within UGT1A1, UGT1A4, UGT1A9, UGT2B7, UGT2B10, and UGT2B17, 47 variants were genotyped, including UGT2B10*2 and UGT2B17*2. The association between variation in these UGTs and glucuronidation activity within European and African American current smokers (n = 128), quantified as urinary ratios of the glucuronide over unconjugated compound for nicotine, cotinine, trans-3′-hydroxycotinine, and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), was investigated in regression models assuming a dominant effect of variant alleles.

Results: Correcting for multiple testing, three UGT2B10 variants were associated with cotinine glucuronidation, rs2331559 and rs11726322 in European Americans and rs835309 in African Americans (P ≤ 0.0002). Additional variants predominantly in UGT2B10 were nominally associated with nicotine (P = 0.008–0.04) and cotinine (P = <0.001–0.02) glucuronidation in both ethnicities in addition to UGT2B10*2 in European Americans (P = 0.01, P < 0.001). UGT2B17*2 (P = 0.03) in European Americans and UGT2B7 variants (P = 0.02–0.04) in African Americans were nominally associated with 3HC glucuronidation. UGT1A (P = 0.007–0.01), UGT2B10 (P = 0.02), and UGT2B7 (P = 0.02–0.03) variants in African Americans were nominally associated with NNAL glucuronidation.

Conclusions: Findings from this initial in vivo study support a role for multiple UGTs in the glucuronidation of tobacco-related compounds in vivo, in particular UGT2B10 and cotinine glucuronidation.

Impact: Findings also provide insight into ethnic differences in glucuronidation activity, which could be contributing to ethnic disparities in the risk for smoking-related cancers. Cancer Epidemiol Biomarkers Prev; 24(1); 94–104. ©2014 AACR.
Data from Genes Associated with Prostate Cancer Are Differentially Expressed in African American and European American Men
Authors: Powell Isaac J. , Dyson Greg , Land Susan , Ruterbusch Julie , Bock Cathryn H. , Lenk Steve , Herawi Mehsati , Everson Richard , Giroux Craig N. , Schwartz Ann G. , Bollig-Fischer Aliccia
Published: April 2023

Abstract
Background: Despite more aggressive screening across all demographics and gradual declines in mortality related to prostate cancer (PCa) in the United States, disparities among populations persist. A substantial proportion of African American men (AAM) have a higher overall incidence, earlier age of onset, increased proportion of clinically advanced disease, and increased bone metastases and mortality from PCa compared to European American men (EAM). Limited early evidence indicates that underlying causes for disparities may be observed in tumor-specific gene expression programs.

Methods: This study used microarray-based methods to measure expression levels for 517 genes that were previously associated with PCa in archived formalin-fixed paraffin embedded (FFPE) specimens; testing the hypothesis that gene expression features of functional consequence to cancer distinguish PCa from AAM and EAM. A t test was conducted comparing AAM to EAM expression levels for each probe on the array.

Results: Analysis of 639 tumor samples (270 AAM, 369 EAM) showed that 95 genes were overexpressed specifically in PCa from AAM relative to EAM and 132 were overexpressed in PCa from EAM relative to AAM. Furthermore, systems-level analyses highlight the relevant signaling pathways and functions associated with the EAM- or AAM-specific overexpressed gene sets, for example, inflammation and lipid metabolism.

Conclusions: Results here bring further understanding to the potential for molecular differences for PCa in AAM versus EAM.

Impact: The results support the notion that therapeutic benefits will be realized when targeted treatments are designed to acknowledge and address a greater spectrum of PCa subtypes and molecular distinctions. Cancer Epidemiol Biomarkers Prev; 22(5); 891–7. ©2013 AACR.
Data from Vasoactive Peptides with Angiogenesis-Regulating Activity Predict Cancer Risk in Males
Authors: Belting Mattias , Almgren Peter , Manjer Jonas , Hedblad Bo , Struck Joachim , Wang Thomas J. , Bergmann Andreas , Melander Olle
Published: April 2023

Abstract
Background: Tumor development requires angiogenesis, and antiangiogenesis has been introduced in the treatment of cancer patients; however, how the cardiovascular phenotype correlates with cancer risk remains ill-defined. Here, we hypothesized that vasoactive peptides previously implicated in angiogenesis regulation predict long-term cancer risk.

Methods: We measured midregional proatrial natriuretic peptide (MR-proANP), proadrenomedullin (MR-proADM), and C-terminal preprovasopressin (copeptin) in fasting plasma from participants of the Malmö Diet and Cancer Study that were free from cancer prior to the baseline exam in 1991 to 1994 (1,768 males and 2,293 females). We used Cox proportional hazards models to determine the time to first cancer event in relation to baseline levels of vasoactive peptides during a median follow-up of 15 years.

Results: First cancer events occurred in 366 males and in 368 females. In males, one SD increase of MR-proANP, copeptin, and MR-proADM was independently related to incident cancer [HR (95% CI)] by 0.85 (0.74–0.96), P = 0.012; 1.17 (1.04–1.32), P = 0.009; and 1.12 (0.99–1.26), P = 0.065, respectively, and a summed biomarker score identified an almost 2-fold difference in cancer risk between the top and bottom quartile (P < 0.001). In younger males, the biomarker score identified a more than 3-fold increase in risk between the top and bottom quartile (P < 0.001). Among females, we found no relationship between biomarkers and cancer incidence.

Conclusions: Our data suggest that vasoactive peptide biomarkers predict cancer risk in males, particularly in younger males.

Impact: Our findings may have implications for cancer risk prediction and present novel, potentially drug modifiable, mechanisms underlying cancer development. Cancer Epidemiol Biomarkers Prev; 21(3); 513–22. ©2012 AACR.
Data from Confounding of the Association between Radiation Exposure from CT Scans and Risk of Leukemia and Brain Tumors by Cancer Susceptibility Syndromes
Authors: Meulepas Johanna M. , Ronckers Cécile M. , Merks Johannes , Weijerman Michel E. , Lubin Jay H. , Hauptmann Michael
Published: April 2023

Abstract
Background: Recent studies linking radiation exposure from pediatric computed tomography (CT) to increased risks of leukemia and brain tumors lacked data to control for cancer susceptibility syndromes (CSS). These syndromes might be confounders because they are associated with an increased cancer risk and may increase the likelihood of CT scans performed in children.

Methods: We identify CSS predisposing to leukemia and brain tumors through a systematic literature search and summarize prevalence and risk estimates. Because there is virtually no empirical evidence in published literature on patterns of CT use for most types of CSS, we estimate confounding bias of relative risks (RR) for categories of radiation exposure based on expert opinion about the current and previous patterns of CT scans among CSS patients.

Results: We estimate that radiation-related RRs for leukemia are not meaningfully confounded by Down syndrome, Noonan syndrome, or other CSS. In contrast, RRs for brain tumors may be overestimated due to confounding by tuberous sclerosis complex (TSC) while von Hippel–Lindau disease, neurofibromatosis type 1, or other CSS do not meaningfully confound. Empirical data on the use of CT scans among CSS patients are urgently needed.

Conclusions: Our assessment indicates that associations with leukemia reported in previous studies are unlikely to be substantially confounded by unmeasured CSS, whereas brain tumor risks might have been overestimated due to confounding by TSC.

Impact: Future studies should identify TSC patients in order to avoid overestimation of brain tumor risks due to radiation exposure from CT scans. Cancer Epidemiol Biomarkers Prev; 25(1); 114–26. ©2015 AACR.