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1.  Genetic Variation in A4GNT in Relation to Helicobacter pylori Serology and Gastric Cancer Risk 
Helicobacter  2009;14(5):120-125.
OBJECTIVES
Helicobacter pylori (H. pylori), a known risk factor of gastric cancer, rarely colonize the deeper portion of normal gastric glands, where the mucus is rich in alpha-1,4-linked N-acetylglucosamine (A4GN) capped O-glycans, that strongly inhibit H. pylori growth in vitro.
METHODS
We investigated the association between genetic variation in the O-glycan transferase encoding gene (A4GNT) and H. pylori infection and gastric cancer risk using a Polish population-based case-control study (273 gastric cancer patients and 377 controls).
RESULTS
A haplotype at the rs2622694-rs397266 locus was associated with H. pylori infection, with the A-A haplotype associated with higher risk compared with the most frequent G-G haplotype (odds ratio 2.30; 95% confidence interval 1.35 – 3.92). The association remained significant after correction for multiple tests (global P value: nominal 0.002, empirical 0.045). Neither this haplotype nor the tagSNPs were associated with overall gastric cancer risk.
CONCLUSION
A4GNT genetic variation may be relevant to H. pylori infection, but not to gastric cancer risk.
doi:10.1111/j.1523-5378.2009.00708.x
PMCID: PMC3008782  PMID: 19751437
2.  Prediagnosis Soy Food Consumption and Lung Cancer Survival in Women 
Journal of Clinical Oncology  2013;31(12):1548-1553.
Purpose
We recently reported an inverse association between soy food intake and lung cancer risk among nonsmoking women. The effect size for aggressive lung cancers was larger than that observed for other types of lung cancer. Therefore, we hypothesized that soy consumption may favorably affect the overall survival of patients with lung cancer.
Patients and Methods
This analysis included 444 women with incident lung cancer identified from the Shanghai Women's Health Study. Prediagnosis soy food intake was assessed at enrollment and reassessed 2 years later. Proportional hazards models were used to evaluate the association between soy food intake and overall survival.
Results
Of the 444 patients with lung cancer, 318 died during follow-up. Initial analyses including all patients showed that higher intake of soy food was associated with better overall survival after adjusting for demographic and lifestyle characteristics and other nonclinical factors. Larger effect sizes for the association were found after additional adjustment for tumor stage and treatment in analyses including 301 patients with data available on these clinical factors. Compared with the median intake of soy food, fully adjusted hazard ratios for total mortality associated with the 10th, 30th, 70th, and 90th percentiles of intake were 1.81 (95% CI, 1.26 to 2.59), 1.25 (95% CI, 1.09 to 1.42), 0.88 (95% CI, 0.80 to 0.97), and 0.89 (95% CI, 0.68 to 1.16), respectively. Similar inverse associations were observed for dietary isoflavone intake.
Conclusion
This study suggests, to the best of our knowledge for the first time, that, among women with lung cancer, prediagnosis intake of soy food is associated with better overall survival.
doi:10.1200/JCO.2012.43.0942
PMCID: PMC3625711  PMID: 23530109
3.  Mobile Phone Use and its Association With Sitting Time and Meeting Physical Activity Recommendations in a Mexican American Cohort 
JMIR mHealth and uHealth  2016;4(2):e54.
Background
The benefits of physical activity (PA) are well-documented. Mobile phones influence PA by promoting screen-based sedentary time, providing prompts or reminders to be active, aiding in tracking and monitoring PA, or providing entertainment during PA. It is not known how mobile phone use is associated with PA and sitting time in Mexican Americans, and how mobile phone users may differ from nonusers.
Objective
To determine the associations between mobile phone use, PA, and sitting time and how these behaviors differ from mobile phone nonusers in a sample of 2982 Mexican-American adults from the Mano a Mano cohort.
Methods
Differences in meeting PA recommendations and sitting time between mobile phone users and nonusers were examined using chi-square and analysis of variance tests. Logistic regression was used to examine associations between mobile phone use, PA, and sitting.
Results
Mobile phone users were more likely to be obese by body mass index criteria (≥30 kg/m2), younger, born in the United States and lived there longer, more educated, and sit more hours per day but more likely to meet PA recommendations than nonusers. Males (odds ratio [OR] 1.42, 95% CI 1.16-1.74), use of text messaging (OR 1.26, 95% CI 1.03-1.56), and having a higher acculturation score (OR 1.27, 95% CI 1.07-1.52) were associated with higher odds of meeting PA recommendations. Sitting more hours per day was associated with being male, obese, born in the United States, a former alcohol drinker, and having at least a high school education. Among nonusers, being born in the United States was associated with higher odds of more sitting time, and being married was associated with higher odds of meeting PA recommendations.
Conclusions
Mobile phone interventions using text messages could be tailored to promote PA in less acculturated and female Mexican American mobile phone users.
doi:10.2196/mhealth.4926
PMCID: PMC4929350  PMID: 27311831
mobile phone; physical activity; Mexican Americans; sedentary lifestyle
4.  Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types 
Sampson, Joshua N. | Wheeler, William A. | Yeager, Meredith | Panagiotou, Orestis | Wang, Zhaoming | Berndt, Sonja I. | Lan, Qing | Abnet, Christian C. | Amundadottir, Laufey T. | Figueroa, Jonine D. | Landi, Maria Teresa | Mirabello, Lisa | Savage, Sharon A. | Taylor, Philip R. | Vivo, Immaculata De | McGlynn, Katherine A. | Purdue, Mark P. | Rajaraman, Preetha | Adami, Hans-Olov | Ahlbom, Anders | Albanes, Demetrius | Amary, Maria Fernanda | An, She-Juan | Andersson, Ulrika | Andriole, Gerald | Andrulis, Irene L. | Angelucci, Emanuele | Ansell, Stephen M. | Arici, Cecilia | Armstrong, Bruce K. | Arslan, Alan A. | Austin, Melissa A. | Baris, Dalsu | Barkauskas, Donald A. | Bassig, Bryan A. | Becker, Nikolaus | Benavente, Yolanda | Benhamou, Simone | Berg, Christine | Van Den Berg, David | Bernstein, Leslie | Bertrand, Kimberly A. | Birmann, Brenda M. | Black, Amanda | Boeing, Heiner | Boffetta, Paolo | Boutron-Ruault, Marie-Christine | Bracci, Paige M. | Brinton, Louise | Brooks-Wilson, Angela R. | Bueno-de-Mesquita, H. Bas | Burdett, Laurie | Buring, Julie | Butler, Mary Ann | Cai, Qiuyin | Cancel-Tassin, Geraldine | Canzian, Federico | Carrato, Alfredo | Carreon, Tania | Carta, Angela | Chan, John K. C. | Chang, Ellen T. | Chang, Gee-Chen | Chang, I-Shou | Chang, Jiang | Chang-Claude, Jenny | Chen, Chien-Jen | Chen, Chih-Yi | Chen, Chu | Chen, Chung-Hsing | Chen, Constance | Chen, Hongyan | Chen, Kexin | Chen, Kuan-Yu | Chen, Kun-Chieh | Chen, Ying | Chen, Ying-Hsiang | Chen, Yi-Song | Chen, Yuh-Min | Chien, Li-Hsin | Chirlaque, María-Dolores | Choi, Jin Eun | Choi, Yi Young | Chow, Wong-Ho | Chung, Charles C. | Clavel, Jacqueline | Clavel-Chapelon, Françoise | Cocco, Pierluigi | Colt, Joanne S. | Comperat, Eva | Conde, Lucia | Connors, Joseph M. | Conti, David | Cortessis, Victoria K. | Cotterchio, Michelle | Cozen, Wendy | Crouch, Simon | Crous-Bou, Marta | Cussenot, Olivier | Davis, Faith G. | Ding, Ti | Diver, W. Ryan | Dorronsoro, Miren | Dossus, Laure | Duell, Eric J. | Ennas, Maria Grazia | Erickson, Ralph L. | Feychting, Maria | Flanagan, Adrienne M. | Foretova, Lenka | Fraumeni, Joseph F. | Freedman, Neal D. | Beane Freeman, Laura E. | Fuchs, Charles | Gago-Dominguez, Manuela | Gallinger, Steven | Gao, Yu-Tang | Gapstur, Susan M. | Garcia-Closas, Montserrat | García-Closas, Reina | Gascoyne, Randy D. | Gastier-Foster, Julie | Gaudet, Mia M. | Gaziano, J. Michael | Giffen, Carol | Giles, Graham G. | Giovannucci, Edward | Glimelius, Bengt | Goggins, Michael | Gokgoz, Nalan | Goldstein, Alisa M. | Gorlick, Richard | Gross, Myron | Grubb, Robert | Gu, Jian | Guan, Peng | Gunter, Marc | Guo, Huan | Habermann, Thomas M. | Haiman, Christopher A. | Halai, Dina | Hallmans, Goran | Hassan, Manal | Hattinger, Claudia | He, Qincheng | He, Xingzhou | Helzlsouer, Kathy | Henderson, Brian | Henriksson, Roger | Hjalgrim, Henrik | Hoffman-Bolton, Judith | Hohensee, Chancellor | Holford, Theodore R. | Holly, Elizabeth A. | Hong, Yun-Chul | Hoover, Robert N. | Horn-Ross, Pamela L. | Hosain, G. M. Monawar | Hosgood, H. Dean | Hsiao, Chin-Fu | Hu, Nan | Hu, Wei | Hu, Zhibin | Huang, Ming-Shyan | Huerta, Jose-Maria | Hung, Jen-Yu | Hutchinson, Amy | Inskip, Peter D. | Jackson, Rebecca D. | Jacobs, Eric J. | Jenab, Mazda | Jeon, Hyo-Sung | Ji, Bu-Tian | Jin, Guangfu | Jin, Li | Johansen, Christoffer | Johnson, Alison | Jung, Yoo Jin | Kaaks, Rudolph | Kamineni, Aruna | Kane, Eleanor | Kang, Chang Hyun | Karagas, Margaret R. | Kelly, Rachel S. | Khaw, Kay-Tee | Kim, Christopher | Kim, Hee Nam | Kim, Jin Hee | Kim, Jun Suk | Kim, Yeul Hong | Kim, Young Tae | Kim, Young-Chul | Kitahara, Cari M. | Klein, Alison P. | Klein, Robert J. | Kogevinas, Manolis | Kohno, Takashi | Kolonel, Laurence N. | Kooperberg, Charles | Kricker, Anne | Krogh, Vittorio | Kunitoh, Hideo | Kurtz, Robert C. | Kweon, Sun-Seog | LaCroix, Andrea | Lawrence, Charles | Lecanda, Fernando | Lee, Victor Ho Fun | Li, Donghui | Li, Haixin | Li, Jihua | Li, Yao-Jen | Li, Yuqing | Liao, Linda M. | Liebow, Mark | Lightfoot, Tracy | Lim, Wei-Yen | Lin, Chien-Chung | Lin, Dongxin | Lindstrom, Sara | Linet, Martha S. | Link, Brian K. | Liu, Chenwei | Liu, Jianjun | Liu, Li | Ljungberg, Börje | Lloreta, Josep | Lollo, Simonetta Di | Lu, Daru | Lund, Eiluv | Malats, Nuria | Mannisto, Satu | Marchand, Loic Le | Marina, Neyssa | Masala, Giovanna | Mastrangelo, Giuseppe | Matsuo, Keitaro | Maynadie, Marc | McKay, James | McKean-Cowdin, Roberta | Melbye, Mads | Melin, Beatrice S. | Michaud, Dominique S. | Mitsudomi, Tetsuya | Monnereau, Alain | Montalvan, Rebecca | Moore, Lee E. | Mortensen, Lotte Maxild | Nieters, Alexandra | North, Kari E. | Novak, Anne J. | Oberg, Ann L. | Offit, Kenneth | Oh, In-Jae | Olson, Sara H. | Palli, Domenico | Pao, William | Park, In Kyu | Park, Jae Yong | Park, Kyong Hwa | Patiño-Garcia, Ana | Pavanello, Sofia | Peeters, Petra H. M. | Perng, Reury-Perng | Peters, Ulrike | Petersen, Gloria M. | Picci, Piero | Pike, Malcolm C. | Porru, Stefano | Prescott, Jennifer | Prokunina-Olsson, Ludmila | Qian, Biyun | Qiao, You-Lin | Rais, Marco | Riboli, Elio | Riby, Jacques | Risch, Harvey A. | Rizzato, Cosmeri | Rodabough, Rebecca | Roman, Eve | Roupret, Morgan | Ruder, Avima M. | de Sanjose, Silvia | Scelo, Ghislaine | Schned, Alan | Schumacher, Fredrick | Schwartz, Kendra | Schwenn, Molly | Scotlandi, Katia | Seow, Adeline | Serra, Consol | Serra, Massimo | Sesso, Howard D. | Setiawan, Veronica Wendy | Severi, Gianluca | Severson, Richard K. | Shanafelt, Tait D. | Shen, Hongbing | Shen, Wei | Shin, Min-Ho | Shiraishi, Kouya | Shu, Xiao-Ou | Siddiq, Afshan | Sierrasesúmaga, Luis | Sihoe, Alan Dart Loon | Skibola, Christine F. | Smith, Alex | Smith, Martyn T. | Southey, Melissa C. | Spinelli, John J. | Staines, Anthony | Stampfer, Meir | Stern, Marianna C. | Stevens, Victoria L. | Stolzenberg-Solomon, Rachael S. | Su, Jian | Su, Wu-Chou | Sund, Malin | Sung, Jae Sook | Sung, Sook Whan | Tan, Wen | Tang, Wei | Tardón, Adonina | Thomas, David | Thompson, Carrie A. | Tinker, Lesley F. | Tirabosco, Roberto | Tjønneland, Anne | Travis, Ruth C. | Trichopoulos, Dimitrios | Tsai, Fang-Yu | Tsai, Ying-Huang | Tucker, Margaret | Turner, Jenny | Vajdic, Claire M. | Vermeulen, Roel C. H. | Villano, Danylo J. | Vineis, Paolo | Virtamo, Jarmo | Visvanathan, Kala | Wactawski-Wende, Jean | Wang, Chaoyu | Wang, Chih-Liang | Wang, Jiu-Cun | Wang, Junwen | Wei, Fusheng | Weiderpass, Elisabete | Weiner, George J. | Weinstein, Stephanie | Wentzensen, Nicolas | White, Emily | Witzig, Thomas E. | Wolpin, Brian M. | Wong, Maria Pik | Wu, Chen | Wu, Guoping | Wu, Junjie | Wu, Tangchun | Wu, Wei | Wu, Xifeng | Wu, Yi-Long | Wunder, Jay S. | Xiang, Yong-Bing | Xu, Jun | Xu, Ping | Yang, Pan-Chyr | Yang, Tsung-Ying | Ye, Yuanqing | Yin, Zhihua | Yokota, Jun | Yoon, Ho-Il | Yu, Chong-Jen | Yu, Herbert | Yu, Kai | Yuan, Jian-Min | Zelenetz, Andrew | Zeleniuch-Jacquotte, Anne | Zhang, Xu-Chao | Zhang, Yawei | Zhao, Xueying | Zhao, Zhenhong | Zheng, Hong | Zheng, Tongzhang | Zheng, Wei | Zhou, Baosen | Zhu, Meng | Zucca, Mariagrazia | Boca, Simina M. | Cerhan, James R. | Ferri, Giovanni M. | Hartge, Patricia | Hsiung, Chao Agnes | Magnani, Corrado | Miligi, Lucia | Morton, Lindsay M. | Smedby, Karin E. | Teras, Lauren R. | Vijai, Joseph | Wang, Sophia S. | Brennan, Paul | Caporaso, Neil E. | Hunter, David J. | Kraft, Peter | Rothman, Nathaniel | Silverman, Debra T. | Slager, Susan L. | Chanock, Stephen J. | Chatterjee, Nilanjan
Background:
Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites.
Methods:
Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers.
Results:
GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, hl 2, on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (ρ = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (ρ = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (ρ = 0.51, SE =0.18), and bladder and lung (ρ = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures.
Conclusion:
Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
doi:10.1093/jnci/djv279
PMCID: PMC4806328  PMID: 26464424
5.  Soluble levels of CD27 and CD30 are associated with risk of non-Hodgkin lymphoma in three Chinese prospective cohorts 
International journal of cancer  2015;137(11):2688-2695.
Prospective studies conducted in Western populations have suggested that alterations in soluble CD27 (sCD27) and soluble CD30 (sCD30), two markers indicative of B-cell activation, are associated with risk of non-Hodgkin lymphoma (NHL). Given that the characteristics of NHL in East Asia differ from the West, and mechanistic commonalities between these populations with respect to the role of intermediate endpoint biomarkers in lymphomagenesis have not been explored, we conducted a pooled nested case-control study from three prospective studies of Chinese men and women including 218 NHL cases and 218 individually matched controls. Compared to the lowest quartile, ORs (95% CIs) for the 2nd, 3rd, and 4th quartiles of sCD27 were 1.60 (0.83-3.09), 1.94 (0.98-3.83), and 4.45 (2.25-8.81), respectively (ptrend = 0.000005). The corresponding ORs for sCD30 were 1.74 (0.85-3.58), 1.86 (0.94-3.67), and 5.15 (2.62-10.12) (ptrend = 0.0000002). These associations remained statistically significant in individuals diagnosed with NHL 10 or more years after blood draw. Notably, the magnitude of the associations with NHL risk was very similar to those in Western populations in previous studies. These findings of the similar association between sCD27 or sCD30 and NHL risk across different populations support an important underlying mechanism of B-cell activation in lymphomagenesis.
doi:10.1002/ijc.29637
PMCID: PMC4898881  PMID: 26095604
CD27; CD30; immune markers; non-Hodgkin lymphoma; East Asians; prospective study
6.  Personalized Risk Assessment in Never, Light, and Heavy Smokers in a prospective cohort in Taiwan 
Scientific Reports  2016;6:36482.
The objective of this study was to develop markedly improved risk prediction models for lung cancer using a prospective cohort of 395,875 participants in Taiwan. Discriminatory accuracy was measured by generation of receiver operator curves and estimation of area under the curve (AUC). In multivariate Cox regression analysis, age, gender, smoking pack-years, family history of lung cancer, personal cancer history, BMI, lung function test, and serum biomarkers such as carcinoembryonic antigen (CEA), bilirubin, alpha fetoprotein (AFP), and c-reactive protein (CRP) were identified and included in an integrative risk prediction model. The AUC in overall population was 0.851 (95% CI = 0.840–0.862), with never smokers 0.806 (95% CI = 0.790–0.819), light smokers 0.847 (95% CI = 0.824–0.871), and heavy smokers 0.732 (95% CI = 0.708–0.752). By integrating risk factors such as family history of lung cancer, CEA and AFP for light smokers, and lung function test (Maximum Mid-Expiratory Flow, MMEF25–75%), AFP and CEA for never smokers, light and never smokers with cancer risks as high as those within heavy smokers could be identified. The risk model for heavy smokers can allow us to stratify heavy smokers into subgroups with distinct risks, which, if applied to low-dose computed tomography (LDCT) screening, may greatly reduce false positives.
doi:10.1038/srep36482
PMCID: PMC5090352  PMID: 27805040
7.  Predictors and long-term reproducibility of urinary phthalate metabolites in middle-aged men and women living in urban Shanghai 
Environment international  2015;84:94-106.
Phthalate esters are man-made chemicals commonly used as plasticizers and solvents, and humans may be exposed through ingestion, inhalation, and dermal absorption. Little is known about predictors of phthalate exposure, particularly in Asian countries. Because phthalates are rapidly metabolized and excreted from the body following exposure, it is important to evaluate whether phthalate metabolites measured at a single point in time can reliably rank exposures to phthalates over a period of time. We examined the concentrations and predictors of phthalate metabolite concentrations among 50 middle-aged women and 50 men from two Shanghai cohorts, enrolled in 1997-2000 and 2002-2006, respectively. We assessed the reproducibility of urinary concentrations of phthalate metabolites in three spot samples per participant taken several years apart (mean interval between first and third sample was 7.5 years [women] or 2.9 years [men]), using Spearman's rank correlation coefficients and intra-class correlation coefficients. We detected ten phthalate metabolites in at least 50% of individuals for two or more samples. Participant sex, age, menopausal status, education, income, body mass index, consumption of bottled water, recent intake of medication, and time of day of collection of the urine sample were associated with concentrations of certain phthalate metabolites. The reproducibility of an individual's urinary concentration of phthalate metabolites across several years was low, with all intra-class correlation coefficients and most Spearman rank correlation coefficients ≤ 0.3. Only mono(2-ethylhexyl) phthalate, a metabolite of di(2-ethylhexyl)phthalate, had a Spearman rank correlation coefficient ≥ 0.4 among men, suggesting moderate reproducibility. These findings suggest that a single spot urine sample is not sufficient to rank exposures to phthalates over several years in an adult urban Chinese population.
doi:10.1016/j.envint.2015.07.003
PMCID: PMC4570864  PMID: 26255822
Phthalates; reproducibility; predictors; food contaminants; personal care products
8.  Pleiotropic analysis of cancer risk loci on esophageal adenocarcinoma risk 
Background
Several cancer-associated loci identified from genome-wide association studies (GWAS) have been associated with risks of multiple cancer sites, suggesting pleiotropic effects. We investigated whether GWAS-identified risk variants for other common cancers are associated with risk of esophageal adenocarcinoma (EA) or its precursor, Barrett's esophagus (BE).
Methods
We examined the associations between risks of EA and BE and 387 single nucleotide polymorphisms (SNPs) that have been associated with risks of other cancers, by using genotype imputation data on 2,163 control participants and 3,885 (1,501 EA and 2,384 BE) case patients from the Barrett's and Esophageal Adenocarcinoma Genetic Susceptibility Study, and investigated effect modification by smoking history, body mass index (BMI), and reflux/heartburn.
Results
After correcting for multiple testing, none of the tested 387 SNPs were statistically significantly associated with risk of EA or BE. No evidence of effect modification by smoking, BMI, or reflux/heartburn was observed.
Conclusions
Genetic risk variants for common cancers identified from GWAS appear not to be associated with risks of EA or BE.
Impact
To our knowledge, this is the first investigation of pleiotropic genetic associations with risks of EA and BE.
doi:10.1158/1055-9965.EPI-15-0596
PMCID: PMC4648999  PMID: 26364162
Pleiotropic analysis; esophageal adenocarcinoma; Barrett's esophagus
9.  A newly identified susceptibility locus near FOXP1 modifies the association of gastroesophageal reflux with Barrett’s esophagus 
Background
Important risk factors for esophageal adenocarcinoma (EA) and its precursor, Barrett’s esophagus (BE) include gastroesophageal reflux disease, obesity, and cigarette-smoking. Recently, genome-wide association studies have identified seven germline single nucleotide polymorphisms (SNPs) that are associated with risk of BE and EA. Whether these genetic susceptibility loci modify previously identified exposure-disease associations is unclear.
Methods
We analyzed exposure and genotype data from the BEACON Consortium discovery phase GWAS, which included 1516 EA case patients, 2416 BE case patients, and 2187 control participants. We examined the seven newly identified susceptibility SNPs for interactions with body mass index, smoking status, and report of weekly heartburn or reflux. Logistic regression models were used to estimate odds ratios for these risk factors stratified by SNP genotype, separately for BE and EA.
Results
The odds ratio for BE associated with at least weekly heartburn or reflux varied significantly with the presence of at least one minor allele of rs2687201 (nominal p-value=0.0005, false discovery rate=0.042). Odds ratios (95% confidence intervals) for weekly heartburn or reflux among participants with 0, 1, or 2 minor alleles of rs2687201 were 6.17 (4.91,7.56), 3.56 (2.85,4.44), and 3.97 (2.47,6.37), respectively. No statistically significant interactions were observed for smoking status and body mass index.
Conclusion
Reflux symptoms are more strongly associated with BE risk among persons homozygous for the major allele of rs2687201, which lies ~75 kb downstream of the transcription factor gene FOXP1.
Impact
The novel gene-exposure interaction discovered in this study provides new insights to the etiology of esophageal adenocarcinoma.
doi:10.1158/1055-9965.EPI-15-0507
PMCID: PMC4816532  PMID: 26377193
esophageal cancer; gastroesophageal reflux disease; gene-environment interaction; genome-wide association study; smoking
10.  Dietary flavonoid intake and Barrett's esophagus in western Washington State 
Annals of epidemiology  2015;25(10):730-735.e2.
Purpose
Flavonoids, concentrated in fruits and vegetables, demonstrate in experimental studies chemopreventive properties in relation to Barrett's esophagus (BE), a precursor lesion for esophageal adenocarcinoma. One case-control investigation reported an inverse association between isoflavone intake and odds of BE, yet no epidemiologic study has considered other flavonoid classes, which are more commonly consumed by Americans.
Methods
We examined intake of total flavonoids, six flavonoid classes, and lignans among case-control study participants in western Washington state. Food frequency questionnaires were self-completed by BE cases with specialized intestinal metaplasia (SIM) (n=170) and matched controls (n=183).
Results
In logistic regression models adjusted for age, sex, body mass index, and energy intake, the odds ratio for SIM BE associated with anthocyanidin intake was 0.49 (95% Confidence Interval: 0.30, 0.80, for quartiles 2-4 combined vs. quartile 1), for which wine and fruit juice were major dietary sources. More moderate decreased odds ratios were noted for flavanones, flavonols, isoflavones, and lignans. A modest increased odds ratio was observed for flavones, for which pizza was the main dietary source in our population.
Conclusions
Our findings of an inverse association between anthocyanidins and odds of BE suggests that adequate dietary intake of these compounds may lower risk of this cancer precursor lesion.
doi:10.1016/j.annepidem.2015.05.010
PMCID: PMC4567908  PMID: 26169148
Barrett's esophagus; diet; epidemiologic studies; flavonoids
11.  Genome-wide association studies in oesophageal adenocarcinoma and Barrett's oesophagus: a large-scale meta-analysis 
The Lancet. Oncology  2016;17(10):1363-1373.
Summary
Background
Oesophageal adenocarcinoma represents one of the fastest rising cancers in high-income countries. Barrett's oesophagus is the premalignant precursor of oesophageal adenocarcinoma. However, only a few patients with Barrett's oesophagus develop adenocarcinoma, which complicates clinical management in the absence of valid predictors. Within an international consortium investigating the genetics of Barrett's oesophagus and oesophageal adenocarcinoma, we aimed to identify novel genetic risk variants for the development of Barrett's oesophagus and oesophageal adenocarcinoma.
Methods
We did a meta-analysis of all genome-wide association studies of Barrett's oesophagus and oesophageal adenocarcinoma available in PubMed up to Feb 29, 2016; all patients were of European ancestry and disease was confirmed histopathologically. All participants were from four separate studies within Europe, North America, and Australia and were genotyped on high-density single nucleotide polymorphism (SNP) arrays. Meta-analysis was done with a fixed-effects inverse variance-weighting approach and with a standard genome-wide significance threshold (p<5 × 10−8). We also did an association analysis after reweighting of loci with an approach that investigates annotation enrichment among genome-wide significant loci. Furthermore, the entire dataset was analysed with bioinformatics approaches—including functional annotation databases and gene-based and pathway-based methods—to identify pathophysiologically relevant cellular mechanisms.
Findings
Our sample comprised 6167 patients with Barrett's oesophagus and 4112 individuals with oesophageal adenocarcinoma, in addition to 17 159 representative controls from four genome-wide association studies in Europe, North America, and Australia. We identified eight new risk loci associated with either Barrett's oesophagus or oesophageal adenocarcinoma, within or near the genes CFTR (rs17451754; p=4·8 × 10−10), MSRA (rs17749155; p=5·2 × 10−10), LINC00208 and BLK (rs10108511; p=2·1 × 10−9), KHDRBS2 (rs62423175; p=3·0 × 10−9), TPPP and CEP72 (rs9918259; p=3·2 × 10−9), TMOD1 (rs7852462; p=1·5 × 10−8), SATB2 (rs139606545; p=2·0 × 10−8), and HTR3C and ABCC5 (rs9823696; p=1·6 × 10−8). The locus identified near HTR3C and ABCC5 (rs9823696) was associated specifically with oesophageal adenocarcinoma (p=1·6 × 10−8) and was independent of Barrett's oesophagus development (p=0·45). A ninth novel risk locus was identified within the gene LPA (rs12207195; posterior probability 0·925) after reweighting with significantly enriched annotations. The strongest disease pathways identified (p<10−6) belonged to muscle cell differentiation and to mesenchyme development and differentiation.
Interpretation
Our meta-analysis of genome-wide association studies doubled the number of known risk loci for Barrett's oesophagus and oesophageal adenocarcinoma and revealed new insights into causes of these diseases. Furthermore, the specific association between oesophageal adenocarcinoma and the locus near HTR3C and ABCC5 might constitute a novel genetic marker for prediction of the transition from Barrett's oesophagus to oesophageal adenocarcinoma. Fine-mapping and functional studies of new risk loci could lead to identification of key molecules in the development of Barrett's oesophagus and oesophageal adenocarcinoma, which might encourage development of advanced prevention and intervention strategies.
Funding
US National Cancer Institute, US National Institutes of Health, National Health and Medical Research Council of Australia, Swedish Cancer Society, Medical Research Council UK, Cambridge NIHR Biomedical Research Centre, Cambridge Experimental Cancer Medicine Centre, Else Kröner Fresenius Stiftung, Wellcome Trust, Cancer Research UK, AstraZeneca UK, University Hospitals of Leicester, University of Oxford, Australian Research Council.
doi:10.1016/S1470-2045(16)30240-6
PMCID: PMC5052458  PMID: 27527254
12.  Cooking Coal Use and All-Cause and Cause-Specific Mortality in a Prospective Cohort Study of Women in Shanghai, China 
Environmental Health Perspectives  2016;124(9):1384-1389.
Background:
Nearly 4.3 million deaths worldwide were attributable to exposure to household air pollution in 2012. However, household coal use remains widespread.
Objectives:
We investigated the association of cooking coal and all-cause and cause-specific mortality in a prospective cohort of primarily never-smoking women in Shanghai, China.
Methods:
A cohort of 74,941 women were followed from 1996 through 2009 with annual linkage to the Shanghai vital statistics database. Cause-specific mortality was identified through 2009. Use of household coal for cooking was assessed through a residential history questionnaire. Cox proportional hazards models estimated the risk of mortality associated with household coal use.
Results:
In this cohort, 63% of the women ever used coal (n = 46,287). Compared with never coal use, ever use of coal was associated with mortality from all causes [hazard ratio (HR) = 1.12; 95% confidence interval (CI): 1.05, 1.21], cancer (HR = 1.14; 95% CI: 1.03, 1.27), and ischemic heart disease (overall HR = 1.61; 95% CI: 1.14, 2.27; HR for myocardial infarction specifically = 1.80; 95% CI: 1.16, 2.79). The risk of cardiovascular mortality increased with increasing duration of coal use, compared with the risk in never users. The association between coal use and ischemic heart disease mortality diminished with increasing years since cessation of coal use.
Conclusions:
Evidence from this study suggests that past use of coal among women in Shanghai is associated with excess all-cause mortality, and from cardiovascular diseases in particular. The decreasing association with cardiovascular mortality as the time since last use of coal increased emphasizes the importance of reducing use of household coal where use is still widespread.
Citation:
Kim C, Seow WJ, Shu XO, Bassig BA, Rothman N, Chen BE, Xiang YB, Hosgood HD III, Ji BT, Hu W, Wen C, Chow WH, Cai Q, Yang G, Gao YT, Zheng W, Lan Q. 2016. Cooking coal use and all-cause and cause-specific mortality in a prospective cohort study of women in Shanghai, China. Environ Health Perspect 124:1384–1389; http://dx.doi.org/10.1289/EHP236
doi:10.1289/EHP236
PMCID: PMC5010399  PMID: 27091488
13.  ABO blood types and cancer risk—A cohort study of 339,432 subjects in Taiwan 
Cancer epidemiology  2015;39(2):150-156.
Background
The associations of laboratory-based ABO phenotypes with cancer risks and mortality have not been systematically determined.
Methods
The study subjects were 339,432 healthy individuals with laboratory-based blood types from a Taiwan cohort.
Results
Compared to blood type O, blood type A was significantly associated with an elevated risk of stomach cancer incidence (Hazard Ratio [HR], 1.38 [95% CI, 1.11–1.72]) and mortality (HR, 1.38 [95% CI, 1.02–1.86]) compared with blood type O, after adjusting for age, sex, education, smoking, alcohol drinking, physical activity, and body mass index. Non-O blood types were associated with an elevated risk of pancreatic cancer, with blood type B reaching statistical significance for incidence (HR, 1.59 [95% CI, 1.02–2.48]) and mortality (HR, 1.63 [95% CI, 1.02–2.60]). In contrast, kidney cancer risk was inversely associated with blood type AB (HR, 0.41 [95% CI, 0.18–0.93]) compared to type O.
Conclusion
Cancer risks vary in people with different ABO blood types, with elevated risks of stomach cancer associated with blood type A and pancreatic cancer associated with non-O blood types (A, B, and AB).
doi:10.1016/j.canep.2014.12.006
PMCID: PMC4993100  PMID: 25600007
ABO blood type; Cancer risk; Cancer mortality; Cohort
14.  Dose-response association between hepatitis B surface antigen levels and liver cancer risk in Chinese men and women 
International journal of cancer  2016;139(2):355-362.
We aimed at evaluating the risk of liver cancer in different levels of HBsAg among Chinese men and women. We carried out a nested case-control study including 363 cases and 3,511 controls in two population-based cohorts in Shanghai. Plasma samples collected at enrollment were quantified for HBsAg levels using the Architect QT assay. Conditional logistic regression was performed to estimate the odds ratios (ORs) and 95% confidence intervals (95%CIs) for liver cancer, with adjustment for potential confounders. HBsAg was detected in 6.29% of control subjects overall (7.02% in men and 4.98% in women). HBsAg levels were positively associated with liver cancer risk in a dose-response manner (Ptrend<0.001). Such association showed a significant gender disparity. With increasing levels of HBsAg, liver cancer risks rose more steeply in men than in women. In men, the adjusted ORs increased from 7.27 (95%CI: 3.49–15.15) at the lowest detectable level of HBsAg (5–9 IU/ml) to 7.16 (95%CI: 3.21–15.96), 34.30 (95%CI: 16.94–69.44), and 47.33 (95%CI: 23.50–95.34) at the highest level of HBsAg (≥1,000 IU/ml) compared to those negative for HBsAg. The corresponding ORs were much lower for women, from 1.37 (95%CI: 0.25–7.47) to 3.81 (95%CI: 1.09–13.28), 7.36 (95%CI: 2.41–22.46), and 16.86 (95%CI: 7.24–39.27), respectively. HBsAg quantification has potential to distinguish individuals at different risks of liver cancer. Men with the lowest detectable level of HBsAg should still pay attention to their liver cancer risks, but those with a higher level may be given a higher priority in future liver cancer surveillance program.
doi:10.1002/ijc.30086
PMCID: PMC4985528  PMID: 26990915
Hepatitis B surface antigen; Liver cancer; Dose-response relationship; Gender disparity; Prospective study
15.  Leukocyte telomere length in relation to the risk of Barrett's esophagus and esophageal adenocarcinoma 
Cancer Medicine  2016;5(9):2657-2665.
Abstract
Chronic inflammation and oxidative damage caused by obesity, cigarette smoking, and chronic gastroesophageal reflux disease (GERD) are major risk factors associated with Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). EAC has been increasing the past few decades, and early discovery and treatment are crucial for survival. Telomere shortening due to cell division and oxidative damage may reflect the impact of chronic inflammation and could possibly be used as predictor for disease development. We examined the prevalence of shorter leukocyte telomere length (LTL) among individuals with GERD, BE, or EAC using a pooled analysis of studies from the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON). Telomere length was measured in leukocyte DNA samples by Q‐PCR. Participants included 1173 patients (386 with GERD, 384 with EAC, 403 with BE) and 736 population‐based controls. The association of LTL (in tertiles) along the continuum of disease progression from GERD to BE to EAC was calculated using study‐specific odds ratios (ORs) and 95% confidence intervals (CIs) from logistic regression models adjusted for potential confounders. Shorter LTL were less prevalent among GERD patients (OR 0.57; 95% CI: 0.35–0.93), compared to population‐based controls. No statistically significant increased prevalence of short/long LTL among individuals with BE or EAC was observed. In contrast to some earlier reports, our findings add to the evidence that leukocyte telomere length is not a biomarker of risk related to the etiology of EAC. The findings do not suggest a relationship between LTL and BE or EAC.
doi:10.1002/cam4.810
PMCID: PMC5055192  PMID: 27384379
Barrett's esophagus; esophageal Adenocarcinoma, epidemiology; telomere
16.  The authors respond. 
doi:10.1097/EDE.0000000000000305
PMCID: PMC4452404  PMID: 25899997
17.  Racial disparities in renal cell carcinoma: a single‐payer healthcare experience 
Cancer Medicine  2016;5(8):2101-2108.
Abstract
Significant racial disparities in survival for renal cell carcinoma (RCC) exist between white and black patients. Differences in access to care and comorbidities are possible contributors. To investigate if racial disparities persist when controlling for access to care, we analyzed data from a single‐payer healthcare system. As part of a case–control study within the Kaiser Permanente Northern California system, pathologic and clinical records were obtained for RCC cases (2152 white, 293 black) diagnosed from 1998 to 2008. Patient demographics, comorbidities, tumor characteristics, and treatment status were compared. Overall survival and disease‐specific survival (DSS) were calculated by the Kaplan–Meier method. A Cox proportion hazards model estimated the independent associations of race, comorbidity, and clinicopathologic variables with DSS. We found that compared to white patients, black patients were diagnosed at a younger age (median 62 vs. 66 years, P < 0.001), were more likely to have papillary RCC (15% vs. 5.2%, P < 0.001), and had similar rates of surgical treatment (78.8% vs. 77.9%, P = 0.764). On multivariate analysis, advanced American Joint Committee on Cancer (AJCC) stage, lack of surgical treatment, larger tumor size, and higher grade were predictors of worse DSS. Race was not an independent predictor of survival. Therefore, we conclude that within a single healthcare system, differences in characteristics of black and white patients with RCC persist; black patients had different comorbidities, were younger, and had decreased tumor stage. However, unlike other series, race was not an independent predictor of DSS, suggesting that survival differences in large registries may result from barriers to healthcare access and/or comorbidity rather than disease biology.
doi:10.1002/cam4.755
PMCID: PMC4884637  PMID: 27228559
Health disparity; kidney cancer; outcome; RCC; survival
18.  Home kitchen ventilation, cooking fuels, and lung cancer risk in a prospective cohort of never smoking women in Shanghai, China 
Indoor air pollution (IAP) caused by cooking has been associated with lung cancer risk in retrospective case-control studies in developing and rural countries. We report the association of cooking conditions, fuel use, oil use and risk of lung cancer in a developed urban population in a prospective cohort of women in Shanghai. A total of 71,320 never smoking women were followed from 1996 through 2009 and 429 incident lung cancer cases were identified. Questionnaires collected information on household living and cooking practices for the women’s three most recent residences and utilization of cooking fuel and oil, and ventilation conditions. Cox proportional hazards regression estimated the association for kitchen ventilation conditions, cooking fuels, and use of cooking oils for the risk of lung cancer by hazard ratios (HR) with 95% confidence intervals (95% CI). Ever poor kitchen ventilation was associated with a 49% increase in lung cancer risk (HR: 1.49; 95% CI: 1.15–1.95) compared to never poor ventilation. Ever use of coal was not significantly associated. However, ever coal use with poor ventilation (HR: 1.69; 95% CI: 1.22–2.35) and twenty or more years of using coal (HR: 2.03; 95% CI: 1.35–3.05) was significantly associated compared to no exposure to coal or poor ventilation. Cooking oil use was not significantly associated. These results demonstrate that IAP from poor ventilation of coal combustion increases the risk of lung cancer and is an important public health issue in cities across China where people may have lived in homes with inadequate kitchen ventilation.
doi:10.1002/ijc.29020
PMCID: PMC4232458  PMID: 24917360
Ventilation; coal; lung cancer; never smoking; women; China; Shanghai
19.  Genetic variants associated with longer telomere length are associated with increased lung cancer risk among never-smoking women in Asia: A report from the Female Lung Cancer Consortium in Asia 
Machiela, Mitchell J | Hsiung, Chao Agnes | Shu, Xiao-Ou | Seow, Wei Jie | Wang, Zhaoming | Matsuo, Keitaro | Hong, Yun-Chul | Seow, Adeline | Wu, Chen | Hosgood, H Dean | Chen, Kexin | Wang, Jiu-Cun | Wen, Wanqing | Cawthon, Richard | Chatterjee, Nilanjan | Hu, Wei | Caporaso, Neil E | Park, Jae Yong | Chen, Chien-Jen | Kim, Yeul Hong | Kim, Young Tae | Landi, Maria Teresa | Shen, Hongbing | Lawrence, Charles | Burdett, Laurie | Yeager, Meredith | Chang, I-Shou | Mitsudomi, Tetsuya | Kim, Hee Nam | Chang, Gee-Chen | Bassig, Bryan A | Tucker, Margaret | Wei, Fusheng | Yin, Zhihua | An, She-Juan | Qian, Biyun | Lee, Victor Ho Fun | Lu, Daru | Liu, Jianjun | Jeon, Hyo-Sung | Hsiao, Chin-Fu | Sung, Jae Sook | Kim, Jin Hee | Gao, Yu-Tang | Tsai, Ying-Huang | Jung, Yoo Jin | Guo, Huan | Hu, Zhibin | Hutchinson, Amy | Wang, Wen-Chang | Klein, Robert J | Chung, Charles C | Oh, In-Jae | Chen, Kuan-Yu | Berndt, Sonja I | Wu, Wei | Chang, Jiang | Zhang, Xu-Chao | Huang, Ming-Shyan | Zheng, Hong | Wang, Junwen | Zhao, Xueying | Li, Yuqing | Choi, Jin Eun | Su, Wu-Chou | Park, Kyong Hwa | Sung, Sook Whan | Chen, Yuh-Min | Liu, Li | Kang, Chang Hyun | Hu, Lingmin | Chen, Chung-Hsing | Pao, William | Kim, Young-Chul | Yang, Tsung-Ying | Xu, Jun | Guan, Peng | Tan, Wen | Su, Jian | Wang, Chih-Liang | Li, Haixin | Sihoe, Alan Dart Loon | Zhao, Zhenhong | Chen, Ying | Choi, Yi Young | Hung, Jen-Yu | Kim, Jun Suk | Yoon, Ho-Il | Cai, Qiuyin | Lin, Chien-Chung | Park, In Kyu | Xu, Ping | Dong, Jing | Kim, Christopher | He, Qincheng | Perng, Reury-Perng | Kohno, Takashi | Kweon, Sun-Seog | Chen, Chih-Yi | Vermeulen, Roel C H | Wu, Junjie | Lim, Wei-Yen | Chen, Kun-Chieh | Chow, Wong-Ho | Ji, Bu-Tian | Chan, John K C | Chu, Minjie | Li, Yao-Jen | Yokota, Jun | Li, Jihua | Chen, Hongyan | Xiang, Yong-Bing | Yu, Chong-Jen | Kunitoh, Hideo | Wu, Guoping | Jin, Li | Lo, Yen-Li | Shiraishi, Kouya | Chen, Ying-Hsiang | Lin, Hsien-Chih | Wu, Tangchun | Wong, Maria Pik | Wu, Yi-Long | Yang, Pan-Chyr | Zhou, Baosen | Shin, Min-Ho | Fraumeni, Joseph F | Zheng, Wei | Lin, Dongxin | Chanock, Stephen J | Rothman, Nathaniel | Lan, Qing
Recent evidence from several relatively small nested case-control studies in prospective cohorts shows an association between longer telomere length measured phenotypically in peripheral white blood cell (WBC) DNA and increased lung cancer risk. We sought to further explore this relationship by examining a panel of 7 telomere-length associated genetic variants in a large study of 5,457 never-smoking female Asian lung cancer cases and 4,493 never-smoking female Asian controls using data from a previously reported genome-wide association study. Using a group of 1,536 individuals with phenotypically measured telomere length in WBCs in the prospective Shanghai Women’s Health study, we demonstrated the utility of a genetic risk score (GRS) of 7 telomere-length associated variants to predict telomere length in an Asian population. We then found that GRSs used as instrumental variables to predict longer telomere length were associated with increased lung cancer risk (OR = 1.51 (95% CI=1.34–1.69) for upper vs. lower quartile of the weighted GRS, P-value=4.54×10−14) even after removing rs2736100 (P-value=4.81×10−3), a SNP in the TERT locus robustly associated with lung cancer risk in prior association studies. Stratified analyses suggested the effect of the telomere-associated GRS is strongest among younger individuals. We found no difference in GRS effect between adenocarcinoma and squamous cell subtypes. Our results indicate that a genetic background that favors longer telomere length may increase lung cancer risk, which is consistent with earlier prospective studies relating longer telomere length with increased lung cancer risk.
doi:10.1002/ijc.29393
PMCID: PMC4733320  PMID: 25516442
association study; genetics; lung cancer; telomere length; genetic risk score
20.  Principal component analysis of dietary and lifestyle patterns in relation to risk of subtypes of esophageal and gastric cancer 
Annals of epidemiology  2011;21(7):543-550.
Purpose
To perform pattern analyses of dietary and lifestyle factors in relation to risk of esophageal and gastric cancers.
Methods
We evaluated risk factors for esophageal adenocarcinoma (EA), esophageal squamous cell carcinoma (ESCC), gastric cardia adenocarcinoma (GCA), and other gastric cancers (OGA) using data from a population-based case-control study conducted in Connecticut, New Jersey, and western Washington state. Dietary/lifestyle patterns were created using principal component analysis (PCA). Impact of the resultant scores on cancer risk was estimated through logistic regression.
Results
PCA identified six patterns: meat/nitrite, fruit/vegetable, smoking/alcohol, legume/meat alternate, GERD/BMI, and fish/vitamin C. Risk of each cancer under study increased with rising meat/nitrite score. Risk of EA increased with increasing GERD/BMI score, and risk of ESCC rose with increasing smoking/alcohol score and decreasing GERD/BMI score. Fruit/vegetable scores were inversely associated with EA, ESCC, and GCA.
Conclusions
PCA may provide a useful approach for summarizing extensive dietary/lifestyle data into fewer interpretable combinations that discriminate between cancer cases and controls. The analyses suggest that meat/nitrite intake is associated with elevated risk of each cancer under study, while fruit/vegetable intake reduces risk of EA, ESCC, and GCA. GERD/obesity were confirmed as risk factors for EA and smoking/alcohol as risk factors for ESCC.
doi:10.1016/j.annepidem.2010.11.019
PMCID: PMC3109225  PMID: 21435900
esophageal adenocarcinoma; gastric cardia adenocarcinoma; esophageal squamous cell carcinoma; diet; principal components
21.  Chronic kidney disease and risk of renal cell carcinoma: differences by race 
Background
The incidence of renal cell carcinoma in the United States differs by race/ethnicity. To better understand these disparities, we conducted a nested case-control study investigating renal cell carcinoma risk factors across racial/ethnic groups within the Kaiser Permanente Northern California health care network.
Methods
Our study included 3,136 renal cell carcinoma cases (2,152 white, 293 black, 425 Hispanic, 255 Asian) diagnosed between 1998 and 2008 and 31,031 individually matched controls (21,478 white, 2,836 black, 4,147 Hispanic, 2,484 Asian). Risk of renal cell carcinoma was assessed in relation to smoking status, body mass index (BMI), hypertension, and chronic kidney disease. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using conditional logistic regression, and population attributable risk (PAR) to estimate by race the proportion of cases attributable to hypertension and chronic kidney disease.
Results
The association between chronic kidney disease and renal cell carcinoma differed markedly by race (Pinteraction<0.001), with associations observed among blacks (OR=10.4 [95% CI=6.0–17.9]), Asians (5.1 [2.2–11.7]), and Hispanics (2.3 [1.1–4.6]) but not whites (1.1 [0.6–1.9]). Hypertension, high BMI, and smoking were associated with renal cell carcinoma, but findings generally did not differ by race. Relative to other racial/ethnic groups, blacks had the highest proportion of renal cell carcinoma incidence attributable to hypertension and chronic kidney disease (combined, PAR=37%; hypertension only, PAR=27%; chronic kidney disease, PAR=10%).
Conclusions
Our findings suggest that hypertension and chronic kidney disease likely have contributed to the observed excess in renal cell carcinoma incidence among blacks compared with whites.
doi:10.1097/EDE.0000000000000205
PMCID: PMC4422505  PMID: 25393631
22.  Historical Occupational Trichloroethylene Air Concentrations Based on Inspection Measurements From Shanghai, China 
Annals of Occupational Hygiene  2014;59(1):62-78.
Purpose:
Trichloroethylene (TCE) is a carcinogen that has been linked to kidney cancer and possibly other cancer sites including non-Hodgkin lymphoma. Its use in China has increased since the early 1990s with China’s growing metal, electronic, and telecommunications industries. We examined historical occupational TCE air concentration patterns in a database of TCE inspection measurements collected in Shanghai, China to identify temporal trends and broad contrasts among occupations and industries.
Methods:
Using a database of 932 short-term, area TCE air inspection measurements collected in Shanghai worksites from 1968 through 2000 (median year 1986), we developed mixed-effects models to evaluate job-, industry-, and time-specific TCE air concentrations.
Results:
Models of TCE air concentrations from Shanghai work sites predicted that exposures decreased 5–10% per year between 1968 and 2000. Measurements collected near launderers and dry cleaners had the highest predicted geometric means (GM for 1986 = 150–190mg m−3). The majority (53%) of the measurements were collected in metal treatment jobs. In a model restricted to measurements in metal treatment jobs, predicted GMs for 1986 varied 35-fold across industries, from 11mg m−3 in ‘other metal products/repair’ industries to 390mg m–3 in ‘ships/aircrafts’ industries.
Conclusions:
TCE workplace air concentrations appeared to have dropped over time in Shanghai, China between 1968 and 2000. Understanding differences in TCE concentrations across time, occupations, and industries may assist future epidemiologic studies in China.
doi:10.1093/annhyg/meu066
PMCID: PMC4290627  PMID: 25180291
China; occupational exposures; population-based studies; statistical model; trichloroethylene
23.  The ability of bilirubin in identifying smokers with higher risk of lung cancer: a large cohort study in conjunction with global metabolomic profiling 
Purpose
We aimed to identify serum metabolites as potential valuable biomarkers for lung cancer and to improve risk stratification in smokers.
Experimental Design
We performed global metabolomic profiling followed by targeted validation of individual metabolites in a case-control design of 386 lung cancer cases and 193 matched controls. We then validated bilirubin, which consistently showed significant differential levels in cases and controls, as a risk marker for lung cancer incidence and mortality in a large prospective cohort comprised of 425,660 participants.
Results
Through global metabolomic profiling and following targeted validation, bilirubin levels consistently showed a statistically significant difference among healthy controls and lung cancer cases. In the prospective cohort, the inverse association was only seen in male smokers, regardless of smoking pack-years and intensity. Compared with male smokers in the highest bilirubin group (>1 mg/dL), those in the lowest bilirubin group (<0.75 mg/dL) had 55% and 66% increase in risks of lung cancer incidence and mortality, respectively. For every 0.1 mg/dL decrease of bilirubin, the risks for lung cancer incidence and mortality increased by 5% and 6% in male smokers, respectively (both P < 0.001). There was a significant interaction between low serum bilirubin level and smoking on lung cancer risk (P for interaction = 0.001).
Conclusion
Low levels of serum bilirubin are associated with higher risks of lung cancer incidence and mortality in male smokers and can be used to identify higher risk smokers for lung cancer.
doi:10.1158/1078-0432.CCR-14-0748
PMCID: PMC4286447  PMID: 25336700
lung cancer; smokers; metabolomics; bilirubin; cohort
24.  Racial disparities in overall survival among renal cell carcinoma patients with young age and small tumors 
Cancer Medicine  2015;5(2):200-208.
Abstract
We examined the overall survival of a population‐based cohort of black and white patients with renal cell carcinoma (RCC) to better understand the paradox of poorer RCC survival despite more frequent diagnosis at lower stage among blacks. Renal cell carcinoma patients (699 white, 252 black) diagnosed between 2002 and 2007 in metropolitan Detroit were followed for vital status in the Detroit Surveillance, Epidemiology and End Results (SEER) registry. Hazard ratios (HR) of death for black versus white race and 95% confidence intervals (CIs) were calculated using Cox proportional hazard models stratified by demographic and prognostic factors, and in models successively adjusted for clinical factors, comorbidities, and socioeconomic factors. Mean follow‐up time was 88.4 months for white patients and 89.6 months for black patients (P = 0.49), with 202 white deaths and 89 black deaths (P = 0.06). While black race was weakly associated with poorer overall survival (P = 0.053), black patients <65 years at diagnosis or with tumors <4 cm in size had significantly poorer survival than their white counterparts (HR = 1.46, 95% CI 1.06–2.01 and HR = 2.15, 95% CI 1.51–3.06, respectively). The racial disparities within these two subgroups were minimally affected by adjustment for clinical/treatment factors (HR = 1.49, 95% CI 1.01–2.19 and HR = 1.95, 95% CI 1.27–2.99), but were substantially reduced when renal‐relevant comorbidities were added (HR = 1.30, 95% CI 0.89–1.91 and HR = 1.76, 95% CI 1.16–2.66). After further adjustment for socioeconomic factors, the survival disparities were essentially null (HR = 1.14, 95% CI 0.71–1.85 and HR = 1.15, 95% CI 0.67–1.98). In this population‐based sample of RCC patients, younger black patients and those with small tumors had poorer overall survival than whites. The disparity was explained primarily by racial differences in renal‐relevant comorbidities, particularly chronic renal failure, and socioeconomic deprivation. Future research should focus on younger patients and those with smaller tumors to better understand how these factors may contribute to the survival disparity.
doi:10.1002/cam4.578
PMCID: PMC4735764  PMID: 26710924
Age; race; renal cell carcinoma; survival; tumor size
25.  Identifying gender differences in reported occupational information from three U.S. population-based case-control studies 
Objectives
Growing evidence suggests that gender-blind assessment of exposure may introduce exposure misclassification, but few studies have characterized gender differences across occupations and industries. We pooled control responses to job-, industry-, and exposure-specific questionnaires (modules) that asked detailed questions about work activities from three US population-based case-control studies to examine gender differences in work tasks and their frequencies.
Methods
We calculated the ratio of female to male controls that completed each module. For four job modules (assembly worker, machinist, health professional, janitor/cleaner) and for subgroups of jobs that completed those modules, we evaluated gender differences in task prevalence and frequency using Chi-square and Mann-Whitney U-tests, respectively.
Results
The 1,360 female and 2,245 male controls reported 6,033 and 12,083 jobs, respectively. Gender differences in female:male module completion ratios were observed for 39 of 45 modules completed by ≥20 controls. Gender differences in task prevalence varied in direction and magnitude. For example, female janitors were significantly more likely to polish furniture (79% vs. 44%), while male janitors were more likely to strip floors (73% vs. 50%). Women usually reported more time spent on tasks than men. For example, the median hours per week spent degreasing for production workers in product manufacturing industries was 6.3 for women and 3.0 for men.
Conclusions
Observed gender differences may reflect actual differences in tasks performed or differences in recall, reporting, or perception, all of which contribute to exposure misclassification and impact relative risk estimates. Our findings reinforce the need to capture subject-specific information on work tasks.
doi:10.1136/oemed-2013-101801
PMCID: PMC4177972  PMID: 24683012
gender; population-based studies; case-control studies; occupational exposure; occupational health

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