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1.  A genome-wide association study of marginal zone lymphoma shows association to the HLA region 
Vijai, Joseph | Wang, Zhaoming | Berndt, Sonja I. | Skibola, Christine F. | Slager, Susan L. | de Sanjose, Silvia | Melbye, Mads | Glimelius, Bengt | Bracci, Paige M. | Conde, Lucia | Birmann, Brenda M. | Wang, Sophia S. | Brooks-Wilson, Angela R. | Lan, Qing | de Bakker, Paul I. W. | Vermeulen, Roel C. H. | Portlock, Carol | Ansell, Stephen M. | Link, Brian K. | Riby, Jacques | North, Kari E. | Gu, Jian | Hjalgrim, Henrik | Cozen, Wendy | Becker, Nikolaus | Teras, Lauren R. | Spinelli, John J. | Turner, Jenny | Zhang, Yawei | Purdue, Mark P. | Giles, Graham G. | Kelly, Rachel S. | Zeleniuch-Jacquotte, Anne | Ennas, Maria Grazia | Monnereau, Alain | Bertrand, Kimberly A. | Albanes, Demetrius | Lightfoot, Tracy | Yeager, Meredith | Chung, Charles C. | Burdett, Laurie | Hutchinson, Amy | Lawrence, Charles | Montalvan, Rebecca | Liang, Liming | Huang, Jinyan | Ma, Baoshan | Villano, Danylo J. | Maria, Ann | Corines, Marina | Thomas, Tinu | Novak, Anne J. | Dogan, Ahmet | Liebow, Mark | Thompson, Carrie A. | Witzig, Thomas E. | Habermann, Thomas M. | Weiner, George J. | Smith, Martyn T. | Holly, Elizabeth A. | Jackson, Rebecca D. | Tinker, Lesley F. | Ye, Yuanqing | Adami, Hans-Olov | Smedby, Karin E. | De Roos, Anneclaire J. | Hartge, Patricia | Morton, Lindsay M. | Severson, Richard K. | Benavente, Yolanda | Boffetta, Paolo | Brennan, Paul | Foretova, Lenka | Maynadie, Marc | McKay, James | Staines, Anthony | Diver, W. Ryan | Vajdic, Claire M. | Armstrong, Bruce K. | Kricker, Anne | Zheng, Tongzhang | Holford, Theodore R. | Severi, Gianluca | Vineis, Paolo | Ferri, Giovanni M. | Ricco, Rosalia | Miligi, Lucia | Clavel, Jacqueline | Giovannucci, Edward | Kraft, Peter | Virtamo, Jarmo | Smith, Alex | Kane, Eleanor | Roman, Eve | Chiu, Brian C. H. | Fraumeni, Joseph F. | Wu, Xifeng | Cerhan, James R. | Offit, Kenneth | Chanock, Stephen J. | Rothman, Nathaniel | Nieters, Alexandra
Nature Communications  2015;6:5751.
Marginal zone lymphoma (MZL) is the third most common subtype of B-cell non-Hodgkin lymphoma. Here we perform a two-stage GWAS of 1,281 MZL cases and 7,127 controls of European ancestry and identify two independent loci near BTNL2 (rs9461741, P=3.95 × 10−15) and HLA-B (rs2922994, P=2.43 × 10−9) in the HLA region significantly associated with MZL risk. This is the first evidence that genetic variation in the major histocompatibility complex influences MZL susceptibility.
Marginal zone lymphoma (MZL) is a common subtype of B-cell non-Hodgkin lymphoma. Here the authors carry out a two-stage genome-wide association study in over 8,000 Europeans and identify two new MZL risk loci at chromosome 6p, implicating the major histocompatibility complex in the disease for the first time.
doi:10.1038/ncomms6751
PMCID: PMC4287989  PMID: 25569183
2.  Efficacy of Neonatal HBV Vaccination on Liver Cancer and Other Liver Diseases over 30-Year Follow-up of the Qidong Hepatitis B Intervention Study: A Cluster Randomized Controlled Trial 
PLoS Medicine  2014;11(12):e1001774.
In a 30-year follow-up of the Qidong Hepatitis B Intervention Study, Yawei Zhang and colleagues examine the effects of neonatal vaccination on liver diseases.
Please see later in the article for the Editors' Summary
Background
Neonatal hepatitis B vaccination has been implemented worldwide to prevent hepatitis B virus (HBV) infections. Its long-term protective efficacy on primary liver cancer (PLC) and other liver diseases has not been fully examined.
Methods and Findings
The Qidong Hepatitis B Intervention Study, a population-based, cluster randomized, controlled trial between 1985 and 1990 in Qidong, China, included 39,292 newborns who were randomly assigned to the vaccination group in which 38,366 participants completed the HBV vaccination series and 34,441 newborns who were randomly assigned to the control group in which the participants received neither a vaccine nor a placebo. However, 23,368 (67.8%) participants in the control group received catch-up vaccination at age 10–14 years. By December 2013, a total of 3,895 (10.2%) in the vaccination group and 3,898 (11.3%) in the control group were lost to follow-up. Information on PLC incidence and liver disease mortality were collected through linkage of all remaining cohort members to a well-established population-based tumor registry until December 31, 2013. Two cross-sectional surveys on HBV surface antigen (HBsAg) seroprevalence were conducted in 1996–2000 and 2008–2012. The participation rates of the two surveys were 57.5% (21,770) and 50.7% (17,204) in the vaccination group and 36.3% (12,184) and 58.6% (17,395) in the control group, respectively. Using intention-to-treat analysis, we found that the incidence rate of PLC and the mortality rates of severe end-stage liver diseases and infant fulminant hepatitis were significantly lower in the vaccination group than the control group with efficacies of 84% (95% CI 23%–97%), 70% (95% CI 15%–89%), and 69% (95% CI 34%–85%), respectively. The estimated efficacy of catch-up vaccination on HBsAg seroprevalence in early adulthood was 21% (95% CI 10%–30%), substantially weaker than that of the neonatal vaccination (72%, 95% CI 68%–75%). Receiving a booster at age 10–14 years decreased HBsAg seroprevalence if participants were born to HBsAg-positive mothers (hazard ratio [HR] = 0.68, 95% CI 0.47–0.97). Limitations to consider in interpreting the study results include the small number of individuals with PLC, participants lost to follow-up, and the large proportion of participants who did not provide serum samples at follow-up.
Conclusions
Neonatal HBV vaccination was found to significantly decrease HBsAg seroprevalence in childhood through young adulthood and subsequently reduce the risk of PLC and other liver diseases in young adults in rural China. The findings underscore the importance of neonatal HBV vaccination. Our results also suggest that an adolescence booster should be considered in individuals born to HBsAg-positive mothers and who have completed the HBV neonatal vaccination series.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Hepatitis B is a life-threatening liver infection caused by the hepatitis B virus (HBV). HBV, which is transmitted through contact with the blood or other bodily fluids of an infected person, can cause both acute (short-term) and chronic (long-term) liver infections. Acute infections rarely cause any symptoms and more than 90% of adults who become infected with HBV (usually through sexual intercourse with an infected partner or through the use of contaminated needles) are virus-free within 6 months. However, in sub-Saharan Africa, East Asia, and other regions where HBV infection is common, HBV is usually transmitted from mother to child at birth or between individuals during early childhood and, unfortunately, most infants who are infected with HBV during the first year of life and many children who are infected before the age of 6 years develop a chronic HBV infection. Such infections can cause liver cancer, liver cirrhosis (scarring of the liver), and other fatal liver diseases. In addition, HBV infection around the time of birth can cause infant fulminant hepatitis, a rare but frequently fatal condition.
Why Was This Study Done?
HBV infections kill about 780,000 people worldwide annually but can be prevented by neonatal vaccination—immunization against HBV at birth. A vaccine against HBV became available in 1982 and many countries now include HBV vaccination at birth followed by additional vaccine doses during early childhood in their national vaccination programs. But, although HBV vaccination has greatly reduced the rate of chronic HBV infection, the protective efficacy of neonatal HBV vaccination against liver diseases has not been fully examined. Here, the researchers investigate how well neonatal HBV vaccination protects against primary liver cancer and other liver diseases by undertaking a 30-year follow-up of the Qidong Hepatitis B intervention Study (QHBIS). This cluster randomized controlled trial of neonatal HBV vaccination was conducted between 1983 and 1990 in Qidong County, a rural area in China with a high incidence of HBV-related primary liver cancer and other liver diseases. A cluster randomized controlled trial compares outcomes in groups of people (towns in this study) chosen at random to receive an intervention or a control treatment (here, vaccination or no vaccination; this study design was ethically acceptable during the 1980s when HBV vaccination was unavailable in rural China but would be unethical nowadays).
What Did the Researchers Do and Find?
The QHBIS assigned nearly 80,000 newborns to receive either a full course of HBV vaccinations (the vaccination group) or no vaccination (the control group); two-thirds of the control group participants received a catch-up vaccination at age 10–14 years. The researchers obtained data on how many trial participants developed primary liver cancer or died from a liver disease during the follow-up period from a population-based tumor registry. They also obtained information on HBsAg seroprevalence—the presence of HBsAg (an HBV surface protein) in the blood of the participants, an indicator of current HBV infection—from surveys undertaken in1996–2000 and 2008–2012. The researchers estimate that the protective efficacy of vaccination was 84% for primary liver cancer (vaccination reduced the incidence of liver cancer by 84%), 70% for death from liver diseases, and 69% for the incidence of infant fulminant hepatitis. Overall, the efficacy of catch-up vaccination on HBsAg seroprevalence in early adulthood was weak compared with neonatal vaccination (21% versus 72%). Notably, receiving a booster vaccination at age 10–14 years decreased HBsAg seroprevalence among participants who were born to HBsAg-positive mothers.
What Do These Findings Mean?
The small number of cases of primary liver cancer and other liver diseases observed during the 30-year follow-up, the length of follow-up, and the availability of incomplete data on seroprevalence all limit the accuracy of these findings. Nevertheless, these findings indicate that neonatal HBV vaccination greatly reduced HBsAg seroprevalence (an indicator of current HBV infection) in childhood and young adulthood and subsequently reduced the risk of liver cancer and other liver diseases in young adults. These findings therefore support the importance of neonatal HBV vaccination. In addition, they suggest that booster vaccination during adolescence might consolidate the efficacy of neonatal vaccination among individuals who were born to HBsAg-positive mothers, a suggestion that needs to be confirmed in randomized controlled trials before booster vaccines are introduced into vaccination programs.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001774.
The World Health Organization provides a fact sheet about hepatitis B (available in several languages) and information about hepatitis B vaccination
The World Hepatitis Alliance (an international not-for-profit, non-governmental organization) provides information about viral hepatitis, including some personal stories about hepatitis B from Bangladesh, Pakistan, the Philippines, and Malawi
The UK National Health Service Choices website provides information about hepatitis B
The not-for-profit British Liver Trust provides information about hepatitis B, including Hepatitis B: PATH B, an interactive educational resource designed to improve the lives of people living with chronic hepatitis B
MedlinePlus provides links to other resources about hepatitis B (in English and Spanish)
Information about the Qidong Hepatitis B intervention Study is available
Chinese Center for Disease Control and Prevention provides links about hepatitis B prevention in Chinese
doi:10.1371/journal.pmed.1001774
PMCID: PMC4280122  PMID: 25549238
3.  Racial Differences in Nasopharyngeal Carcinoma in the United States 
Cancer epidemiology  2013;37(6):10.1016/j.canep.2013.08.008.
Background
Nasopharyngeal carcinoma (NPC) is a malignant neoplasm arising from the mucosal epithelium of the nasopharynx. Different races can have different etiology, presentation, and progression patterns.
Methods
Data were analyzed on NPC patients in the United States reported to the SEER (Surveillance, Epidemiology, and End Results) database between 1973 and 2009. Racial groups studied included non-Hispanic whites, Hispanic whites, blacks, Asians, and others. Patient characteristics, age-adjusted incidence and mortality rates, treatment, and five-year relative survival rates were compared across races. Stratification by stage at diagnosis and histologic type was considered. Multivariate regression was conducted to evaluate the significance of racial differences.
Results
Patient characteristics that were significantly different across races included age at diagnosis, histologic type, in situ/malignant tumors in lifetime, stage, grade, and regional nodes positive. Incidence and mortality rates were significantly different across races, with Asians having the highest rates overall and stratified by age and/or histologic type. Asians also had the highest rate of receiving radiation only. The racial differences in treatment were significant in the multivariate stratified analysis. When stratified by stage and histologic type, Asians had the best five-year survival rates. The survival experience of other races depended on stage and type. In the multivariate analysis, the racial differences were significant.
Conclusions
Analysis of the SEER data shows that racial differences exist among NPC patients in the U.S. This result can be informative to cancer epidemiologists and clinicians.
doi:10.1016/j.canep.2013.08.008
PMCID: PMC3851929  PMID: 24035238
nasopharyngeal carcinoma; racial differences; SEER
4.  Identification of gene–environment interactions in cancer studies using penalization 
Genomics  2013;102(4):10.1016/j.ygeno.2013.08.006.
High-throughput cancer studies have been extensively conducted, searching for genetic markers associated with outcomes beyond clinical and environmental risk factors. Gene–environment interactions can have important implications beyond main effects. The commonly-adopted single-marker analysis cannot accommodate the joint effects of a large number of markers. The existing joint-effects methods also have limitations. Specifically, they may suffer from high computational cost, do not respect the “main effect, interaction” hierarchical structure, or use ineffective techniques. We develop a penalization method for the identification of important G × E interactions and main effects. It has an intuitive formulation, respects the hierarchical structure, accommodates the joint effects of multiple markers, and is computationally affordable. In numerical study, we analyze prognosis data under the AFT (accelerated failure time) model. Simulation shows satisfactory performance of the proposed method. Analysis of an NHL (non-Hodgkin lymphoma) study with SNP measurements shows that the proposed method identifies markers with important implications and satisfactory prediction performance.
doi:10.1016/j.ygeno.2013.08.006
PMCID: PMC3869641  PMID: 23994599
Gene–environment interaction; Penalized marker identification; Cancer prognosis
5.  Role of One-carbon Metabolizing Pathway Genes and Gene-Nutrient Interaction in the Risk of Non-Hodgkin Lymphoma 
Cancer causes & control : CCC  2013;24(10):1875-1884.
Purpose
Genetic polymorphisms in one-carbon metabolizing pathway genes have been associated with risk of malignant lymphoma. However, the results have been inconsistent. The objectives of this study were to examine the potential relationship between gene-nutrient interactions and the risk of non-Hodgkin lymphoma (NHL).
Methods
We examined 25 polymorphisms in 16 one-carbon metabolism genes for their main effect and gene-nutrient interactions in relation to NHL risk among 518 incident cases and 597 population-based controls of Connecticut women enrolled between 1996 and 2000.
Results
A significantly reduced risk of NHL was associated with the homozygous TT genotype in CBS (rs234706, Ex9+33C>T) (OR = 0.51, 95%CI, 0.31–0.84), the homozygous CC genotype in MBD2 (rs603097, −2176C>T) (OR = 0.37, 95%CI, 0.17–0.79), the heterozygote AG genotype in FTHFD (rs1127717, Ex21+31A>G) (OR = 0.73, 95%CI, 0.55–0.98), and a borderline significantly reduced risk of NHL was observed for the homozygous CC genotype in MTRR (rs161870, Ex5+136T>C) (OR = 0.23, 95%CI, 0.05–1.04). The reduced risk of NHL associated with these genotypes was predominately in those with higher dietary vitamin B6 and methionine intakes, as well as with higher dietary folate intake although results were less stable. A borderline significantly increased risk of NHL was also observed for CBS (rs1801181, Ex13+41C>T), FTHFD (rs2305230, Ex10-40G>T), SHMT1 (rs1979277, Ex12+138C>T), and SHMT1 (rs1979276, Ex12+236T>C), and these associations appeared to be contingent on dietary nutrient intakes.
Conclusion
Our results suggest that variation in several one-carbon metabolizing pathway genes may influence the risk of NHL through gene-nutrient interactions involving dietary nutrient intakes.
doi:10.1007/s10552-013-0264-3
PMCID: PMC3951097  PMID: 23913011
dietary nutrients; folate; one-carbon metabolizing genes; non-Hodgkin lymphoma; cancer
6.  Polymorphisms in JAK/STAT Signaling Pathway Genes and Risk of Non-Hodgkin Lymphoma 
Leukemia research  2013;37(9):1120-1124.
Impaired function of Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway genes leads to immunodeficiency and various hematopoietic disorders. We evaluated the association between genetic polymorphisms (SNPs) in 12 JAK/STAT pathway genes (JAK3, STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, STAT6, SCOS1, SCOS2, SCOS3, and SCOS4) and NHL risk in a population-based case-control study of Connecticut women. We identified three SNPs in STAT3 (rs12949918 and rs6503695) and STAT4 (rs932169) associated with NHL risk after adjustment for multiple comparison. Our results suggest that genetic variation in JAK/STAT pathway genes may play a role in lymphomagenesis and warrants further investigation.
doi:10.1016/j.leukres.2013.05.003
PMCID: PMC3998836  PMID: 23768868
JAK/STAT signaling pathway; Non-Hodgkin Lymphoma; polymorphism; case-control study
7.  Birth Weight Reference Percentiles for Chinese 
PLoS ONE  2014;9(8):e104779.
Objective
To develop a reference of population-based gestational age-specific birth weight percentiles for contemporary Chinese.
Methods
Birth weight data was collected by the China National Population-based Birth Defects Surveillance System. A total of 1,105,214 live singleton births aged ≥28 weeks of gestation without birth defects during 2006–2010 were included. The lambda-mu-sigma method was utilized to generate percentiles and curves.
Results
Gestational age-specific birth weight percentiles for male and female infants were constructed separately. Significant differences were observed between the current reference and other references developed for Chinese or non-Chinese infants.
Conclusion
There have been moderate increases in birth weight percentiles for Chinese infants of both sexes and most gestational ages since 1980s, suggesting the importance of utilizing an updated national reference for both clinical and research purposes.
doi:10.1371/journal.pone.0104779
PMCID: PMC4134219  PMID: 25127131
8.  Second to fourth digit ratio, handedness and testicular germ cell tumors 
Early human development  2013;89(7):463-466.
Background
Research on early life exposures and testicular germ cell tumors (TGCT) risk has focused on a possible perinatal etiology with a well-known hypothesis suggesting that hormonal involvement during fetal life is associated with risk. Second-to-fourth digit ratio (2D:4D) and left hand dominance have been proposed as markers of prenatal hormone exposure.
Aim
To evaluate associations between 2D:4D digit ratio, right minus left 2D:4D (ΔR-L), and left-hand dominance and TGCT in the U.S. Servicemen’s Testicular Tumor Environmental and Endocrine Determinants (STEED) Study.
Methods
A total of 246 TGCT cases and 236 non-testicular cancer controls participated in the current study, and completed a self-administered questionnaire. Associations between digit ratio, hand dominance and TGCT were estimated using unconditional logistic regression adjusting for identified covariates.
Results
Right 2D:4D was not associated with TGCT [OR for a one-standard deviation (SD) increase in right hand 2D:4D: 1.12, 95% CI: 0.93–1.34]. The results were consistent when evaluating the association based on the left hand. The difference between right and left hand 2D:4D was also not associated with TGCT risk [OR for a one-SD increase in ΔR-L: 1.03, 95% CI: 0.87–1.23]. Compared to men who reported right-hand dominance, ambidexterity [OR (95% CI) = 0.65 (0.30–1.41)] and left-hand dominance [OR (95% CI) = 0.79 (0.44–1.44)] were not associated with risk.
Conclusions
These results do not support the hypothesis that prenatal hormonal imbalance is associated with TGCT risk. Given the limited sample size, further evaluation of the relationship between TGCT and prenatal hormonal factors using digit ratio, ΔR-L, or left-hand dominance and larger sample size are warranted.
doi:10.1016/j.earlhumdev.2013.04.001
PMCID: PMC3684556  PMID: 23623693
case-control; testicular cancer; hand pattern; left-handed dominance; digit ratio
9.  Single nucleotide polymorphisms in genes encoding for CC chemokines were not associated with the risk of Non-Hodgkin Lymphoma 
Background
Chemokines play a pivotal role in immune regulation and response, and previous studies suggest an association between immune deficiency and Non-Hodgkin lymphoma (NHL).
Methods
We evaluated the association between NHL and polymorphisms in 18 genes (CCL1, CCL2, CCL5, CCL7, CCL8, CCL11, CCL13, CCL18, CCL20, CCL24, CCL26, CCR1, CCR3, CCR4, CCR6, CCR7, CCR8 and CCR9) encoding for the CC chemokines using data from a population-based case-control study of NHL conducted in Connecticut women.
Results
CCR8 was associated with diffuse large B-cell lymphoma (DLBCL) (p = 0.012) and CCL13 was associated with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) (p = 0.003) at gene level. After adjustment for multiple comparisons, none of the genes or SNPs were associated with risk of overall NHL or NHL subtypes.
Conclusions
Our results suggest that the genes encoding for CC chemokines are not significantly associated with the risk of NHL, and further studies are needed to verify these findings.
Impact
Our data indicate that CC chemokine genes were not associated with NHL risk.
doi:10.1158/1055-9965.EPI-13-0328
PMCID: PMC3753095  PMID: 23640258
Non-Hodgkin lymphoma; CC chemokine gene; Single nucleotide polymorphism
10.  Polymorphisms in DNA Repair Pathway Genes, Body Mass Index, and Risk of Non-Hodgkin Lymphoma 
American journal of hematology  2013;88(7):606-611.
We conducted a population-based case-control study in Connecticut women to test the hypothesis that genetic variations in DNA repair pathway genes may modify the relationship between body mass index (BMI) and risk of non-Hodgkin lymphoma (NHL). Compared to those with BMI < 25, women with BMI ≥ 25 had significantly increased risk of NHL among women who carried BRCA1 (rs799917) CT/TT, ERCC2 (rs13181) AA, XRCC1 (rs1799782) CC, and WRN (rs1801195) GG genotypes, but no increase in NHL risk among women who carried BRCA1 CC, ERCC2 AC/CC, XRCC1 CT/TT, and WRN GT/TT genotypes. A significant interaction with BMI was only observed for WRN (rs1801195, P=0.004) for T-cell lymphoma and ERCC2 (rs13181, P=0.002) for diffuse large B-cell lymphoma. The results suggest that common genetic variation in DNA repair pathway genes may modify the association between BMI and NHL risk.
doi:10.1002/ajh.23463
PMCID: PMC3902049  PMID: 23619945
Non-Hodgkin lymphoma; BMI; polymorphisms; DNA repair genes
11.  Subtype of Dietary Fat in Relation to Risk of Hodgkin Lymphoma: A Population-based Case-Control Study in Connecticut and Massachusetts 
Cancer causes & control : CCC  2013;24(3):485-494.
Few epidemiological studies have examined the relationship between dietary fat, which may affect immune function, and risk of Hodgkin lymphoma (HL). The aim of this study was to test the hypothesis that high dietary intake of fat and specific subtypes of fat is associated with the risk of HL among 486 HL cases and 630 population-based controls recruited between 1997–2000 in Connecticut and Massachusetts. Unconditional logistic regression was used to calculate odds ratios (OR) and 95 % confidence intervals (CIs) stratified by age and gender. Among younger adults, HL risk was significantly and positively associated with higher intake of saturated fat (ORs for increasing quartiles= 1.3, 1.8, and 2.1; p trend = 0.04), and negatively associated with higher intake of monounsaturated fat (ORs for increasing quartiles= 0.5, 0.5, and 0.4; p trend = 0.03), after adjustment for potential confounders including lifestyle and other dietary factors. The associations with saturated fat (ORs for increasing quartile = 2.4, 3.2, and 4.4; p trend < 0.01) and monounsaturated fat (ORs for increasing quartile= 0.3, 0.6, and 0.3; p trend = 0.04) were most apparent in younger women, whereas there was no significant association between intake of total fat or any type of fat and risk of HL in older females or younger or older males. These findings show that the associations between dietary fat and risk of HL may vary by gender and age, and require confirmation in other populations.
doi:10.1007/s10552-012-0136-2
PMCID: PMC4044911  PMID: 23314676
Hodgkin lymphoma; dietary fat; saturated fat; monounsaturated fat
12.  Personal Use of Hair Dye and the Risk of Certain Subtypes of Non-Hodgkin Lymphoma 
American journal of epidemiology  2008;167(11):1321-1331.
Personal use of hair dye has been inconsistently linked to risk of non-Hodgkin lymphoma (NHL), perhaps because of small samples or a lack of detailed information on personal hair-dye use in previous studies. This study included 4,461 NHL cases and 5,799 controls from the International Lymphoma Epidemiology Consortium 1988–2003. Increased risk of NHL (odds ratio (OR) = 1.3, 95% confidence interval (CI): 1.1, 1.4) associated with hair-dye use was observed among women who began using hair dye before 1980. Analyses by NHL subtype showed increased risk for follicular lymphoma (FL) and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) but not for other NHL subtypes. The increased risks of FL (OR = 1.4, 95% CI: 1.1, 1.9) and CLL/SLL (OR = 1.5, 95% CI: 1.1, 2.0) were mainly observed among women who started using hair dyes before 1980. For women who began using hair dye in 1980 or afterward, increased FL risk was limited to users of dark-colored dyes (OR = 1.5, 95% CI: 1.1, 2.0). These results indicate that personal hair-dye use may play a role in risks of FL and CLL/SLL in women who started use before 1980 and that increased risk of FL among women who started use during or after 1980 cannot be excluded.
doi:10.1093/aje/kwn058
PMCID: PMC4025953  PMID: 18408225
case-control studies; hair dyes; lymphoma; non-Hodgkin
13.  Risk factors of HBV intrauterine transmission among HBsAg-positive pregnant women 
Journal of viral hepatitis  2012;20(5):317-321.
Little is known about the risk factors associated with hepatitis B virus (HBV) intrauterine transmission among HBsAg positive mothers. We conducted a study in Taiyuan, China including 1,133 HBsAg positive mothers and their babies. A total of 101 neonates had HBsAg and/or HBV DNA positive with an intrauterine transmission rate of 8.9%. Maternal menstrual irregularity (OR=4.95, 95%CI: 1.71, 14.33) and severe nausea during the first trimester (OR=1.86, 95%CI: 1.11, 3.09) were associated with an increased risk of intrauterine transmission, while cesarean delivery (OR=0.32, 95%CI: 0.20, 0.51) was associated with a decreased risk after adjusting for potential confounders. Maternal HBeAg positive was a strong independent predictor for intrauterine transmission (OR=2.56, 95%CI: 1.54, 4.27). A positive association between maternal HBV DNA levels and intrauterine transmission was suggested. Maternal HBIG administration during pregnancy, family history of HBV infection, and premature rupture of membranes were not associated with the risk of intrauterine transmission. The study confirmed that maternal HBeAg positive was a risk factor and cesarean delivery was a protective factor for intrauterine transmission. The new findings associated with menstrual irregularity and severe nausea during the first trimester warrant further investigation.
doi:10.1111/jvh.12032
PMCID: PMC3623007  PMID: 23565613
China; Epidemiology; HBV; HBV DNA; HBeAg; HBsAg; intrauterine transmission
14.  The Risk of Second Cancers After Diagnosis of Primary Thyroid Cancer Is Elevated in Thyroid Microcarcinomas 
Thyroid  2013;23(5):575-582.
Background
Thyroid cancers have increased dramatically over the past few decades. Comorbidities may be important, and previous studies have indicated elevated second cancer risk after initial primary thyroid cancers. This study examined the risk of second cancers after development of a thyroid cancer, primary utilizing the Surveillance, Epidemiology, and End Results (SEER) program database.
Methods
The cohort consisted of men and women diagnosed with first primary thyroid cancer who were reported to a SEER database in 1973–2008 (n=52,103). Standardized incidence ratios (SIR) were calculated for all secondary cancers. Confidence intervals and p-values are at 0.05 significance alpha level and are two-sided based on Poisson exact methods.
Results
In this cohort, 4457 individuals developed second cancers. The risk of developing second cancers after a primary thyroid cancer varied from 10% to 150% depending on different cancer types. Cancers in all sites, breast, skin, prostate, kidney, brain, salivary gland, second thyroid, lymphoma, myeloma, and leukemia were elevated. The magnitude of the risk varied by histology, tumor size, calendar year of first primary thyroid cancer diagnosis, and the treatment of the primary thyroid cancer. The risk of a second cancer was elevated in patients whose first primary thyroid carcinomas were small, or were diagnosed after 1994, or in whom some form of radiation treatment was administered.
Conclusions
This large population-based analysis of second cancers among thyroid cancer patients suggests that there was an increase of second cancers in all sites, and the most commonly elevated second cancers were the salivary gland and kidney. Additionally, the increase in second cancers in patients with recently diagnosed thyroid microcarcinomas (<10 mm) suggests that aggressive radiation treatment of the first primary thyroid cancer, the environment, and genetic susceptibility, may increase the risk of a second cancer.
doi:10.1089/thy.2011.0406
PMCID: PMC3643257  PMID: 23237308
15.  Extent of lymph node dissection: common hepatic artery lymph node dissection can be omitted for esophageal squamous cell carcinoma 
Journal of Thoracic Disease  2014;6(Suppl 3):S325-S332.
Objectives
Controversy persists regarding the adequate extent of lymph node (LN) dissection in thoracic esophageal cancer (EC) surgery. Oncologic efficacy should be balanced with the increased risk of postoperative complications after aggressive radical LN dissection. Here, we evaluate the effectiveness of common hepatic artery LN dissection in surgery for thoracic esophageal squamous cell carcinoma.
Patients and methods
Among a total of 1,563 EC patients who underwent surgery from May 2005 to December 2012 at the Fudan University Shanghai Cancer Center, 1,248 thoracic esophageal squamous cell carcinoma were selected for this study, including 682 patients who underwent esophagectomy with common hepatic artery LN dissection and 566 patients who underwent esophagectomy without common hepatic artery LN dissection. The clinical data of patients were retrospectively analyzed. In addition, the locoregional LN metastasis, relationship between metastatic rates of common hepatic artery LN and clinicopathological factors were analyzed. A propensity score match analysis were performed to control for potential differences in the characteristics of patients with EC cell carcinoma, and postoperative complications were analyzed after propensity score-matching.
Results
The metastatic rate of common hepatic LN was 3.5%. Logistic regression analysis revealed tumor diameter, N classification and pTNM stage were risk factors for common hepatic LN metastasis. Matching based on propensity scores produced 361 patients in each group. The overall incidence of postoperative complications was 32.70% and 35.45%, respectively, no significant difference was found (P=0.432).
Conclusions
The metastatic rate of common hepatic artery LN is low. For patients who undergo resection for Stage I thoracic esophageal squamous cell carcinoma, the dissection of common hepatic artery LN may be safely omitted.
doi:10.3978/j.issn.2072-1439.2014.04.33
PMCID: PMC4037418  PMID: 24876938
Esophageal squamous cell carcinoma; common hepatic artery lymph node (common hepatic artery LN); lymph node dissection (LN dissection); propensity score match
16.  Hepatitis C and Non-Hodgkin Lymphoma Among 4784 Cases and 6269 Controls From the International Lymphoma Epidemiology Consortium 
Background & Aims
Increasing evidence points towards a role of hepatitis C virus (HCV) infection in causing malignant lymphomas. We pooled case-control study data to provide robust estimates of the risk of non-Hodgkin’s lymphoma (NHL) subtypes after HCV infection.
Methods
The analysis included 7 member studies from the International Lymphoma Epidemiology Consortium (InterLymph) based in Europe, North America, and Australia. Adult cases of NHL (n = 4784) were diagnosed between 1988 and 2004 and controls (n = 6269) were matched by age, sex, and study center. All studies used third-generation enzyme-linked immunosorbent assays to test for antibodies against HCV in serum samples. Participants who were human immunodeficiency virus positive or were organ-transplant recipients were excluded.
Results
HCV infection was detected in 172 NHL cases (3.60%) and in 169 (2.70%) controls (odds ratio [OR], 1.78; 95% confidence interval [CI], 1.40–2.25). In subtype-specific analyses, HCV prevalence was associated with marginal zone lymphoma (OR, 2.47; 95% CI, 1.44–4.23), diffuse large B-cell lymphoma (OR, 2.24; 95% CI, 1.68–2.99), and lymphoplasmacytic lymphoma (OR, 2.57; 95% CI, 1.14–5.79). Notably, risk estimates were not increased for follicular lymphoma (OR, 1.02; 95% CI, 0.65–1.60).
Conclusions
These results confirm the association between HCV infection and NHL and specific B-NHL subtypes (diffuse large B-cell lymphoma, marginal zone lymphoma, and lymphoplasmacytic lymphoma).
doi:10.1016/j.cgh.2008.02.011
PMCID: PMC3962672  PMID: 18387498
17.  Body Size and Risk of Hodgkin Lymphoma by Age and Gender: A Population-based Case-Control Study in Connecticut and Massachusetts 
Cancer causes & control : CCC  2012;24(2):287-295.
Purpose
Descriptive studies have indicated a rising trend in Hodgkin lymphoma (HL) incidence in young adults, especially females. Increasing evidence has suggested that some risk factors associated with HL may vary by age or gender. Recent studies have reported an increased risk of HL associated with increasing body mass index (BMI), but the results have been inconsistent. The objectives of this study were to examine whether the associations between measures of body size (height, weight, and BMI) and HL risk vary by age and/or gender.
Methods
A population-based case-control study was conducted in Connecticut and Massachusetts. A total of 567 HL cases and 679 controls were recruited in 1997–2000. Unconditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CIs).
Results
Among younger women < 35 years old, being overweight (25–29.9 kg/m2) vs. normal weight (18.5–24.9 kg/m2) was significantly associated with an increased risk of HL (OR = 2.1, 95% CI = 1.1–4.0). The risk increased with increasing weight and BMI (P trends < 0.01). Among women ≥ 35 years old, by contrast, higher weight and BMI were associated with a reduced risk of HL (P trends < 0.01). Conversely, there was no significant association between BMI and risk of HL in younger or older males.
Conclusions
These findings show that the associations between body size and risk of HL vary by gender and age, and require confirmation in other populations.
doi:10.1007/s10552-012-0100-1
PMCID: PMC3557669  PMID: 23208661
Hodgkin lymphoma; body size; body mass index; height; weight
18.  Genome-wide Association Study Identifies Multiple Risk Loci for Chronic Lymphocytic Leukemia 
Berndt, Sonja I. | Skibola, Christine F. | Joseph, Vijai | Camp, Nicola J. | Nieters, Alexandra | Wang, Zhaoming | Cozen, Wendy | Monnereau, Alain | Wang, Sophia S. | Kelly, Rachel S. | Lan, Qing | Teras, Lauren R. | Chatterjee, Nilanjan | Chung, Charles C. | Yeager, Meredith | Brooks-Wilson, Angela R. | Hartge, Patricia | Purdue, Mark P. | Birmann, Brenda M. | Armstrong, Bruce K. | Cocco, Pierluigi | Zhang, Yawei | Severi, Gianluca | Zeleniuch-Jacquotte, Anne | Lawrence, Charles | Burdette, Laurie | Yuenger, Jeffrey | Hutchinson, Amy | Jacobs, Kevin B. | Call, Timothy G. | Shanafelt, Tait D. | Novak, Anne J. | Kay, Neil E. | Liebow, Mark | Wang, Alice H. | Smedby, Karin E | Adami, Hans-Olov | Melbye, Mads | Glimelius, Bengt | Chang, Ellen T. | Glenn, Martha | Curtin, Karen | Cannon-Albright, Lisa A. | Jones, Brandt | Diver, W. Ryan | Link, Brian K. | Weiner, George J. | Conde, Lucia | Bracci, Paige M. | Riby, Jacques | Holly, Elizabeth A. | Smith, Martyn T. | Jackson, Rebecca D. | Tinker, Lesley F. | Benavente, Yolanda | Becker, Nikolaus | Boffetta, Paolo | Brennan, Paul | Foretova, Lenka | Maynadie, Marc | McKay, James | Staines, Anthony | Rabe, Kari G. | Achenbach, Sara J. | Vachon, Celine M. | Goldin, Lynn R | Strom, Sara S. | Lanasa, Mark C. | Spector, Logan G. | Leis, Jose F. | Cunningham, Julie M. | Weinberg, J. Brice | Morrison, Vicki A. | Caporaso, Neil E. | Norman, Aaron D. | Linet, Martha S. | De Roos, Anneclaire J. | Morton, Lindsay M. | Severson, Richard K. | Riboli, Elio | Vineis, Paolo | Kaaks, Rudolph | Trichopoulos, Dimitrios | Masala, Giovanna | Weiderpass, Elisabete | Chirlaque, María-Dolores | Vermeulen, Roel C H | Travis, Ruth C. | Giles, Graham G. | Albanes, Demetrius | Virtamo, Jarmo | Weinstein, Stephanie | Clavel, Jacqueline | Zheng, Tongzhang | Holford, Theodore R | Offit, Kenneth | Zelenetz, Andrew | Klein, Robert J. | Spinelli, John J. | Bertrand, Kimberly A. | Laden, Francine | Giovannucci, Edward | Kraft, Peter | Kricker, Anne | Turner, Jenny | Vajdic, Claire M. | Ennas, Maria Grazia | Ferri, Giovanni M. | Miligi, Lucia | Liang, Liming | Sampson, Joshua | Crouch, Simon | Park, Ju-hyun | North, Kari E. | Cox, Angela | Snowden, John A. | Wright, Josh | Carracedo, Angel | Lopez-Otin, Carlos | Bea, Silvia | Salaverria, Itziar | Martin, David | Campo, Elias | Fraumeni, Joseph F. | de Sanjose, Silvia | Hjalgrim, Henrik | Cerhan, James R. | Chanock, Stephen J. | Rothman, Nathaniel | Slager, Susan L.
Nature genetics  2013;45(8):868-876.
doi:10.1038/ng.2652
PMCID: PMC3729927  PMID: 23770605
19.  Integrative Analysis of Cancer Prognosis Data with Multiple Subtypes Using Regularized Gradient Descent 
Genetic epidemiology  2012;10.1002/gepi.21669.
In cancer research, high-throughput profiling studies have been extensively conducted, searching for genes/SNPs associated with prognosis. Despite seemingly significant differences, different subtypes of the same cancer (or different types of cancers) may share common susceptibility genes. In this study, we analyze prognosis data on multiple subtypes of the same cancer, but note that the proposed approach is directly applicable to the analysis of data on multiple types of cancers. We describe the genetic basis of multiple subtypes using the heterogeneity model, which allows overlapping but different sets of susceptibility genes/SNPs for different subtypes. An accelerated failure time (AFT) model is adopted to describe prognosis. We develop a regularized gradient descent approach, which conducts gene-level analysis and identifies genes that contain important SNPs associated with prognosis. The proposed approach belongs to the family of gradient descent approaches, is intuitively reasonable, and has affordable computational cost. Simulation study shows that when prognosis-associated SNPs are clustered in a small number of genes, the proposed approach outperforms alternatives with significantly more true positives and fewer false positives. We analyze an NHL (non-Hodgkin lymphoma) prognosis study with SNP measurements, and identify genes associated with the three major subtypes of NHL, namely DLBCL, FL and CLL/SLL. The proposed approach identifies genes different from using alternative approaches and has the best prediction performance.
doi:10.1002/gepi.21669
PMCID: PMC3729731  PMID: 22851516
Integrative analysis; Cancer Prognosis; Gradient descent; NHL; SNP
20.  Occupational solvent exposure, genetic variation in immune genes, and the risk for non-Hodgkin lymphoma 
Solvent exposure has been inconsistently linked to the risk for non-Hodgkin lymphoma (NHL). The aim of this study was to determine whether the association is modified by genetic variation in immune genes. A population-based case–control study involving 601 incident cases of NHL and 717 controls was carried out in 1996–2000 among women from Connecticut. Thirty single nucleotide polymorphisms in 17 immune genes were examined in relation to the associations between exposure to various solvents and the risk for NHL. The study found that polymorphism in interleukin 10 (IL10; rs1800890) modified the association between occupational exposure to organic solvents and the risk for diffuse large B-cell lymphoma (Pfor interaction=0.0058). The results remained statistically significant after adjustment for false discovery rate. Compared with women who were never occupationally exposed to any organic solvents, women who were exposed to organic solvents at least once had a significantly increased risk for diffuse large B-cell lymphoma if they carried the IL10 (rs1800890) TT genotype (odds ratio=3.31, 95% confidence interval: 1.80–6.08), but not if they carried the AT/AA genotype (odds ratio=1.14, 95% confidence interval: 0.72–1.79). No significant interactions were observed for other immune gene single nucleotide polymorphisms and various solvents in relation to NHL overall and its major subtypes. The study provided preliminary evidence supporting a role of immune gene variations in modifying the association between occupational solvent exposure and the risk for NHL.
doi:10.1097/CEJ.0b013e328354d2c1
PMCID: PMC3469764  PMID: 22609637
immune genes; non-Hodgkin lymphoma; occupational exposure; single nucleotide polymorphism; solvents
21.  Smoking, variation in N-acetyltransferase 1 (NAT1) and 2 (NAT2), and risk of non-Hodgkin lymphoma: a pooled analysis within the InterLymph consortium 
Cancer causes & control : CCC  2012;24(1):125-134.
Purpose
Studies of smoking and risk of non-Hodgkin lymphoma (NHL) have yielded inconsistent results, possibly due to subtype heterogeneity and/or genetic variation impacting the metabolism of tobacco-derived carcinogens, including substrates of the N-acetyltransferase enzymes NAT1 and NAT2.
Methods
We conducted a pooled analysis of 5,026 NHL cases and 4,630 controls from seven case–control studies in the international lymphoma epidemiology consortium to examine associations between smoking, variation in the N-acetyltransferase genes NAT1 and NAT2, and risk of NHL subtypes. Smoking data were harmonized across studies, and genetic variants in NAT1 and NAT2 were used to infer acetylation phenotype of the NAT1 and NAT2 enzymes, respectively. Pooled odds ratios (ORs) and 95 % confidence intervals (95 % CIs) for risk of NHL and subtypes were calculated using joint fixed effects unconditional logistic regression models.
Results
Current smoking was associated with a significant 30 % increased risk of follicular lymphoma (n = 1,176) but not NHL overall or other NHL subtypes. The association was similar among NAT2 slow (OR 1.36; 95 % CI 1.07–1.75) and intermediate/rapid (OR 1.27; 95 % CI 0.95–1.69) acetylators (pinteraction = 0.82) and also did not differ by NAT1*10 allelotype. Neither NAT2 phenotype nor NAT1*10 allelotype was associated with risk of NHL overall or NHL subtypes.
Conclusion
The current findings provide further evidence for a modest association between current smoking and follicular lymphoma risk and suggest that this association may not be influenced by variation in the N-acetyltransferase enzymes.
doi:10.1007/s10552-012-0098-4
PMCID: PMC3529854  PMID: 23160945
Non-Hodgkin lymphoma; Gene environment interaction; Cigarette smoking; N-acetyltransferase; Follicular lymphoma
22.  Occupational Solvent Exposure, Genetic Variation of DNA Repair Genes, and Risk of Non-Hodgkin Lymphoma 
Objective
To test the hypothesis that genetic variations in DNA repair genes may modify the association between occupational exposure to solvents and the risk of non-Hodgkin lymphoma (NHL).
Methods
A population-based case-control study was conducted in Connecticut women including 518 histologically confirmed incident NHL cases and 597 controls. Unconditional logistic regression models were used to estimate odds ratios (OR) and effect modification from the 30 SNPs in 16 DNA repair genes of the association between solvent exposure and risk of NHL overall and subtypes.
Results
SNPs in MGMT (rs12917) and NBS1 (rs1805794) significantly modified the association between exposure to chlorinated solvents and NHL risk (Pforinteraction = 0.0003 and 0.0048 respectively). After stratified by major NHL histological subtypes, MGMT (rs12917) modified the association between chlorinated solvents and risk of diffuse large B-cell lymphoma (Pforinteraction = 0.0027) and follicular lymphoma (Pforinteraction = 0.0024). A significant interaction was also observed between occupational exposure to benzene and BRCA2 (rs144848) for NHL overall (Pforinteraction = 0.0042).
Conclusions
Our study results suggest that genetic variations in DNA repair genes modify the association between occupational exposure to solvents and risk of NHL.
doi:10.1097/CEJ.0b013e328351c762
PMCID: PMC3397155  PMID: 22430443
Non-Hodgkin Lymphoma; Occupational Exposure; Solvents; Single Nucleotide Polymorphism; DNA Repair Genes
23.  Dietary fiber intake and risk of breast cancer by menopausal and estrogen receptor status 
European journal of nutrition  2012;52(1):217-223.
Purpose
Evaluate the hypothesis that relation of breast cancer associated with dietary fiber intakes varies by type of fiber, menopausal, and the tumor’s hormone receptor status.
Methods
A case-control study of female breast cancer was conducted in Connecticut. A total of 557 incident breast cancer cases and 536 age frequency-matched controls were included in the analysis. Information on dietary intakes was collected through in-person interviews with a semi-quantitative food frequency questionnaire and was converted into nutrient intakes. Odds ratios and 95% confidence intervals were estimated by unconditional logistic regression.
Results
Among pre-menopausal women, higher intake of soluble fiber (highest versus lowest quartile of intake) was associated with a significantly reduced risk of breast cancer (OR = 0.38, 95% CI, 0.15–0.97, Ptrend = 0.08). When further restricted to pre-menopausal women with ER− tumors, the adjusted OR for the highest quartile of intake was 0.15 (95% CI, 0.03–0.69, Ptrend = 0.02) for soluble fiber intake. Among post-menopausal women, no reduced risk of breast cancer was observed for either soluble or insoluble fiber intakes or among ER+ or ER− tumor groups.
Conclusions
The results from this study show that dietary soluble fiber intake is associated with a significantly reduced risk of ER− breast cancer among pre-menopausal women. Additional studies with larger sample size are needed to confirm these results.
doi:10.1007/s00394-012-0305-9
PMCID: PMC3709253  PMID: 22350922
Dietary fiber intake; Breast cancer; Estrogen receptor; Menopausal status; Case-control studies
24.  Pulmonary benign metastasizing leiomyoma from uterine leiomyoma 
Background
Benign metastasizing leiomyoma (BML) occurs in a low proportion of uterine leiomyomas and treatment methods for BML are diverse and controversial. The study introduces preliminary experiences in the diagnosis and treatment of BML with the purpose of finding a suitable management strategy for these patients.
Methods
Three patients with BML were treated in our department from April 2008 to July 2012. Each of these patients presented with multiple nodules in both lungs, where we performed video-assisted thoracoscopic wedge resection to harvest enough tissue for histopathologic and immunohistochemical examination. The patients were treated with medical castration or surgical castration after the diagnosis of BML.
Results
The ultimate pathologic results ruled out the possibility of leiomyosarcoma and other metastatic diseases, and confirmed that the pulmonary lesions were BML. The lung lesions remained stable in two patients who were treated by surgical castration, and the lung nodules regressed in one patient treated with gonadotropin-releasing hormone analogues.
Conclusions
The diagnosis of BML is based on the medical history of uterine myomas and histopathologic and immunohistochemical examination of lung nodules. Video-assisted thoracoscopic wedge resection is the best way to harvest tissue for diagnosis. The better outcomes in BML seem to call for medical intervention, either chemical or surgical, after diagnosis is made.
doi:10.1186/1477-7819-11-163
PMCID: PMC3722006  PMID: 23866077
Benign neoplasms; Castration; Metastasis; Pulmonary; Rare diseases
25.  Sexual Functioning among Testicular Cancer Survivors: A Case-Control Study in the U.S. 
Objective
Sexual function among testicular cancer survivors is a concern because affected men are of reproductive age when diagnosed. We conducted a case-control study among United States military men to examine whether testicular cancer survivors experienced impaired sexual function.
Methods
A total of 246 testicular cancer cases and 236 ethnicity and age matched controls were enrolled in the study in 2008-2009. The Brief Male Sexual Function Inventory (BMSFI) was used to assess sexual function.
Results
Compared to controls, cases scored significantly lower on sex drive (5.77 vs. 5.18), erection (9.40 vs. 8.63), ejaculation (10.83 vs. 9.90), and problem assessment (10.55 vs. 9.54). Cases were significantly more likely to have impaired erection (OR 1.72; 95% CI 1.11-2.64), ejaculation (OR 2.27; 95% CI 1.32-3.91), and problem assessment (OR 2.36; 95% CI 1.43-3.90). In histology and treatment analysis, nonseminoma, chemotherapy and radiation treated cases risk of erectile dysfunction, delayed ejaculation, and/or problem assessment were greater when compared to controls.
Conclusion
This study provides evidence that testicular cancer survivors are more likely to have impaired sexual functioning compared to demographically matched controls. The observed impaired sexual functioning appeared to vary by treatment regimen and histologic subtype.
doi:10.1016/j.jpsychores.2012.02.011
PMCID: PMC3374934  PMID: 22691563
Testicular cancer; sexual function; military men

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