bluuebunny/crossref_metadata_2025_split huggingface dataset:
UV Dose Determines Key Characteristics of Nonmelanoma Skin Cancer
Authors: Ramos Juan , Villa Jaime , Ruiz Abigail , Armstrong Roy , Matta Jaime 
Published: June 2022

Abstract
Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), known as nonmelanoma skin cancer (NMSC), are the most common cancers worldwide. Although many factors are involved in the pathogenesis of NMSC, UV radiation is an important risk factor. A fundamental question in skin cancer research is whether varying doses of total UV radiation influence key characteristics of NMSC. The hypothesis that differences in UV doses influence the BCC/SCC ratio, number of tumors, and anatomic location of the tumor was investigated in 311 participants having 326 tumors and with exposure to a broad range of UV doses. An epidemiologic questionnaire was given to each participant soliciting detailed information on exposure to solar radiation. Environmental UVA and UVB doses were measured continually for 6 years at a permanent UV monitoring station. The total ratio of BCC/SCC was 3.5. Participants who received low and high UV doses had a BCC/SCC ratio of 4.2. Those who received very high UV doses had a ratio of 2.1. A very high UV dose was also associated with the doubling of the total number of tumors per person and a significantly increased risk of having SCC, a more aggressive malignancy. Tumors in sun-exposed areas (on the body) were more common in participants who received high and very high UV doses. The tumors in sun-protected areas were associated with exposure to lower levels of UV. This large-scale population study provides evidence that varying doses of UV radiation have a profound influence on key characteristics of NMSC.
Identifying and Characterizing Adolescent Smoking Trajectories
Authors: Audrain-McGovern Janet , Rodriguez Daniel , Tercyak Kenneth P. , Cuevas Jocelyn , Rodgers Kelli , Patterson Freda 
Published: June 2022

Abstract
Our understanding of longitudinal patterns of adolescent smoking development and the determinants of these patterns is limited. The present study evaluated adolescent smoking trajectories and characterized these trajectories with social, psychological, and behavioral factors in a cohort of adolescents assessed annually from grades 9 to 12. Complete data (smoking practices, novelty seeking, academic performance, substance use, peer smoking, physical activity and sports participation, and tobacco ad receptivity) were available on 968 participants; data were analyzed using latent class growth modeling. Four adolescent smoking trajectories emerged: never smokers, experimenters, earlier/faster smoking adopters, and later/slower smoking adopters. Early adopters were characterized by their high novelty seeking personality, depressive symptoms, poorer academic performance, and receptivity to tobacco advertising, as well as their exposure to other smokers, and use of other substances. Later adopters were characterized quite similarly to the early adopters, although they tended to perform better in school and to be more involved in sports. Experimenters also shared many of these same risk characteristics but to a lesser degree. Overall, never smokers were the most conventional in their profile. These data suggest that there is significant heterogeneity in the timing, rate, and intensity of smoking progression. Adolescent smoking prevention and intervention programs will need to consider this heterogeneity and tailor or enhance attention to risk and protective factors depending on the subpopulation.
ERCC2 Genotypes and a Corresponding Haplotype Are Linked with Breast Cancer Risk in a German Population
Authors: Justenhoven Christina , Hamann Ute , Pesch Beate , Harth Volker , Rabstein Sylvia , Baisch Christian , Vollmert Caren , Illig Thomas , Ko Yon-Dschun , Brüning Thomas , Brauch Hiltrud ,   for the Interdisciplinary Study Group on Gene Environment Interactions and Breast Cancer in Germany Network
Published: June 2022

Abstract
The polygenic concept of breast cancer susceptibility calls for the identification of genetic variants that contribute to breast cancer risk. Reduced DNA repair proficiencies in women with breast cancer pointed to a possible role of DNA repair enzymes in the risk to develop the disease. The nucleotide excision repair enzyme encoded by the excision repair cross-complementing group 2 gene ERCC2 (formerly XPD) known to cause skin cancer by germ line mutations has multiple regulatory cellular functions, including nucleotide excision repair, basal transcription, cell cycle control, and apoptosis. ERCC2 polymorphisms ERCC2_6540_G&gt;A (Asp312Asn) and ERCC2_18880_A&gt;C (Lys751Gln) within the coding region of this evolutionarily highly conserved gene have been of functional relevance and therefore are potential candidates to confer breast cancer susceptibility. Using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, we analyzed genotype frequencies in constitutional DNA of study participants of a German case-control study that included 688 cases of incident breast cancer and 724 population-based, age-matched controls. We identified ERCC2_6540_GG (Asp312Asp) as an at-risk genotype [odds ratio (OR), 2.06; 95% confidence interval (95% CI), 1.39-3.07]. The ERCC2_6540_GG-associated breast cancer risk was even higher in women who were also carriers of the ERCC2_18880_CC (Gln751Gln) genotype (OR, 3.69; 95% CI, 1.76-7.74). We identified ERCC2_6540_G/ERCC2_18880_C (Asp312/Gln751) as the most potent risk-conferring haplotype (OR, 3.49; 95% CI, 2.30-5.28). To our knowledge, this is the first study assigning breast cancer risk to both the ERCC2 genotype encoding Asp312Asp and the haplotype encoding Asp312/Gln751.
Synergistic Effects of STK15 Gene Polymorphisms and Endogenous Estrogen Exposure in the Risk of Breast Cancer
Authors: Dai Qi , Cai Qiu-Yin , Shu Xiao-Ou , Ewart-Toland Amanda , Wen Wan-Qing , Balmain Allan , Gao Yu-Tang , Zheng Wei 
Published: June 2022

Abstract
STK15 is a member of a family of serine/threonine kinases that act as key regulators of chromosome segregation and cytokinesis. Over expression of the STK15 gene leads to centrosome amplification, chromosomal instability, aneuploidy, and transformation. It has been reported that the 91T → A (Phe → Ile at codon 31) polymorphism in the STK15 gene affects the function of this gene. We hypothesized that this polymorphism may interact with endogenous estrogen exposure in the risk of breast cancer and evaluated this hypothesis in a population-based, case-control study conducted among Chinese women in Shanghai. Genotyping assays were completed for 1,102 incident cases and 1,186 community controls. Participation and blood donation rates were over 90% and 80%, respectively. Elevated risks of breast cancer were found to be associated with the Phe/Ile [odds ratio (OR), 1.3; 95% confidence interval (CI), 1.0-1.7] and Ile/Ile (OR, 1.2; 95% CI, 0.9-1.6) genotypes at codon 31 of the STK15 gene, although the ORs were not statistically significant. The risk associated with this polymorphism was modified by factors related to endogenous estrogen exposure, such as high body mass index (BMI), high waist-to-hip ratio, long duration of lifetime menstruation, or long duration of menstruation before first live birth. In particular, a statistically significant interaction was found between BMI and the STK15 Phe31Ile polymorphism (P = 0.02) and a positive association with breast cancer risk for the Ile allele was found only among overweight (BMI ≥ 25 kg/m2) women with adjusted ORs (95% CIs) of 3.3 (1.4-7.7) and 4.1 (1.7-9.8) associated with the Phe/Ile and Ile/Ile genotypes (Pfor trend &lt;0.01), respectively. The findings from this study are consistent with the evidence from invitro and in vivo experiments, implicating an etiologic role of the STK15 gene in human breast cancer, and provide evidence for the modifying effects of genetic background on human cancer risk.
The Economic Impact of False-Positive Cancer Screens
Authors: Lafata Jennifer Elston , Simpkins Janine , Lamerato Lois , Poisson Laila , Divine George , Johnson Christine Cole 
Published: June 2022

AbstractObjective: Despite the promotion and widespread use of routine cancer screening, little is known about the economic consequences of false-positive screening results. We evaluated the medical and nonmedical costs associated with false-positive prostate, lung, colorectal, and ovarian cancer screens.Method: We identified 1,087 Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial participants enrolled in a large managed care organization. Medical care use and costs were compiled from automated sources and trial data. Nonmedical care costs to patients with a false-positive lung cancer screen were obtained by telephone interview (n = 98).Results: Forty-three percent of the study sample incurred at least one false-positive cancer screen. The majority of these patients (83%) received follow-up care. Prior to and after controlling for participant characteristics, significantly higher medical care expenditures in the year following screening were found among those with a false-positive screen. The adjusted mean difference was $1,024 for women and $1,171 for men. Among lung cancer screening patients, few nonmedical care costs were identified beyond the time (mean, 1.5 hours) spent receiving care.Conclusion: The results here indicate that false-positive results among some available cancer screening tests are relatively common, that patients incurring a false-positive screen tend to receive follow-up testing, and that such follow-up is not without associated medical costs. Along with trials evaluating the health benefits of available cancer screening modalities, investigations into potential undesirable consequences of cancer screening are also warranted.
Short Tandem Repeat Polymorphism and Cancer Risk: Influence of Laboratory Analysis on Epidemiologic Findings
Authors: Tran Nguyet , Bharaj Bupinder S. , Diamandis Eleftherios P. , Smith Mylinh , Li Benjamin D. L. , Yu Herbert 
Published: June 2022

Abstract
Short tandem repeats (STR) are common polymorphisms in the genome. The length of STR may influence gene transcription, exhibiting diverse phenotypes. Two STRs, one trinucleotide repeats in the androgen receptor (AR) gene and one dinucleotide repeats in the insulin-like growth factor-I (IGF-I) gene, have been studied for their role in cancer, and the results are conflicting. Although there are many reasons for inconsistent findings, laboratory issues are often overlooked. DNA sizing analysis is regularly used to determine the length of STR, but its analytic validity has not been evaluated in epidemiologic studies. To examine if sizing analysis can reliably determine dinucleotide STR, we compared the method with direct DNA sequencing in analyzing CA repeats in the IGF-I gene in a small case-control study. The study enrolled 75 breast cancer cases and 75 age- and race-matched controls. DNA was extracted from buffy coats and was analyzed for CA repeats by both DNA sizing and direct sequencing. Our comparison indicated that these methods detected the same number of repeats in the short allele but not in the long allele. There was a substantial discrepancy between the methods in determining homozygous alleles. Although the two methods showed &lt;10% of samples having an exact match on the number of repeats in both alleles, both techniques were able to detect a genotype-phenotype correlation and a racial disparity in the genotype. An association between breast cancer risk and IGF-I genotype was found in sequencing analysis but not in sizing analysis. Overall, the comparison suggests that laboratory analysis of dinucleotide STR may not be as reliable as originally thought. This unreliability in STR analysis may result in inconsistent study findings.
Colorectal Cancer and the Methylenetetrahydrofolate Reductase 677C → T and Methionine Synthase 2756A → G Polymorphisms: A Study of 2,168 Case-Control Pairs from the JANUS Cohort
Authors: Ulvik Arve , Vollset Stein Emil , Hansen Svein , Gislefoss Randi , Jellum Egil , Ueland Per Magne 
Published: June 2022

Abstract
Polymorphisms in genes involved in the metabolism of folate and methyl groups have been implicated with risk of colorectal cancer. We evaluated the relation between the polymorphisms 677C → T of the methylenetetrahydrofolate reductase (MTHFR) and 2756A → G of the methionine synthase (MTR) genes and risk of colorectal cancer. From the Norwegian JANUS cohort of 309,000 subjects, 2,179 cases were identified and a similar number of controls were selected. The controls were matched for age, gender, time, and place of serum donation. Genotypes were obtained from 2,168 case-control pairs by real-time PCR of serum samples. Risk of colorectal cancer was estimated with conditional and unconditional logistic regression. Median age at diagnosis was 60 years and mean follow-up 13 years. The odds ratio for MTHFR TT versus CC was 0.73 [95% confidence interval (95% CI), 0.58-0.92] and for MTR GG versus AA was 0.65 (95% CI, 0.47-0.90). No interaction between the polymorphisms was found. Relative risk estimates were similar for men and women, and for young and old age at diagnosis. For the MTR GG genotype, risk reduction was observed at the two most distal sites (sigmoideum and rectum) only (P = 0.003). The folate marker, serum total homocysteine (tHcy), was measured in 1,837 subjects. Odds ratio for the upper versus the lower tertile of tHcy was 1.32 (95% CI, 1.04-1.68). No significant effect modification by tHcy levels was detected for either polymorphism. In summary, we found significantly reduced risk of colorectal cancer in subjects with the MTHFR 677 TT and MTR 2756 GG genotypes. No interaction between the polymorphisms, or of either polymorphism with tHcy, was detected.
Amount, Type, and Timing of Recreational Physical Activity in Relation to Colon and Rectal Cancer in Older Adults: the Cancer Prevention Study II Nutrition Cohort
Authors: Chao Ann , Connell Cari J. , Jacobs Eric J. , McCullough Marjorie L. , Patel Alpa V. , Calle Eugenia E. , Cokkinides Vilma E. , Thun Michael J. 
Published: June 2022

AbstractPhysical activity has consistently been associated with lower risk of colon cancer, but information is limited on the amount, type, and timing of activities. The relationship between physical activity and rectal cancer is unclear. We examined characteristics of recreational physical activity in relation to colon and rectal cancer in the Cancer Prevention Study II Nutrition Cohort of 70,403 men and 80,771 women (median age, 63 years); 940 colon and 390 rectal cancers were identified from enrollment in 1992 to 1993 through August 1999. The multivariate-adjusted rate ratios (95% confidence intervals) associated with any recreational physical activity compared with none were 0.87 (0.71-1.06) for colon cancer and 0.70 (0.53-0.93) for rectal cancer. Colon cancer risk decreased significantly with increasing total hours (P for trend without reference group = 0.007) and metabolic equivalent hours (P for trend = 0.006) per week of activities. No clear decrease in rectal cancer risk was seen with increasing hours per week of physical activity. Rate ratios (95% confidence intervals) were 0.72 (0.52-0.98) for &lt;2 hours, 0.68 (0.47-0.97) for 2 to 3 hours, 0.59 (0.41-0.83) for 4 to 6 hours, and 0.83 (0.59-1.16) for ≥7 hours per week of physical activity compared with none. Past exercise, as reported in 1982, was not associated with risk of either colon or rectal cancer. We conclude that increasing amounts of time spent at recreational physical activity are associated with substantially lower risk of colon cancer and that recreational physical activity is associated with lower risk of rectal cancer in older men and women.
Physical Activity in Relation to All-Site and Lung Cancer Incidence and Mortality in Current and Former Smokers
Authors: Alfano Catherine M. , Klesges Robert C. , Murray David M. , Bowen Deborah J. , McTiernan Anne , Vander Weg Mark W. , Robinson Leslie A. , Cartmel Brenda , Thornquist Mark D. , Barnett Matt , Goodman Gary E. , Omenn Gilbert S. 
Published: June 2022

Abstract
Increased physical activity has been associated with a reduction in the incidence and mortality from all-site cancer and some site-specific cancers in samples of primarily nonsmoking individuals; however, little is known about whether physical activity is associated with similar risk reductions among smokers and ex-smokers. This study examined physical activity in relation to all-site cancer and lung cancer incidence and mortality in a sample of current and former smokers (n = 7,045; 59% male; 95% Caucasian; mean age, 63 years) drawn from the β-Carotene and Retinol Efficacy Trial, a lung cancer chemoprevention trial. Hazard rate ratios and 95% confidence intervals associated with a 1 SD increase in physical activity were 0.86 (0.80-0.94) for all-site cancer only among men, 0.84 (0.69-1.03) for lung cancer only for younger participants, 0.75 (0.59-0.94) for cancer mortality among younger participants and 0.68 (0.53-0.89) among women, and 0.69 (0.53-0.90) for lung cancer mortality only among women. These results suggest that incidence may be more attenuated by physical activity for men and mortality more attenuated for women. Effects may be more pronounced for younger people and may differ inconsistently by pack-years of smoking. Physical activity may play a role in reducing cancer risk and mortality among those with significant tobacco exposure. Prospective studies using more sophisticated measures of physical activity assessed at multiple time points during follow-up are needed to corroborate these associations.
Variants of the IL8 and IL8RB Genes and Risk for Gastric Cardia Adenocarcinoma and Esophageal Squamous Cell Carcinoma
Authors: Savage Sharon A. , Abnet Christian C. , Mark Steven D. , Qiao You-Lin , Dong Zhi-Wei , Dawsey Sanford M. , Taylor Philip R. , Chanock Stephen J. 
Published: June 2022

Abstract
The population of Linxian in north central China is at high risk for gastric cardia adenocarcinoma (GCC) and esophageal squamous cell carcinoma (ESCC), and chronic inflammation may contribute to this risk. Interleukin-8 (IL8), a potent chemoattractant, has three well-characterized single nucleotide polymorphisms (SNP), one (−251) of which alters transcriptional activity. Four well-described SNPs in the two IL8 receptors, IL8RA and IL8RB, have been associated with inflammation. We conducted a case-cohort study in the Nutrition Intervention Trials (Linxian, China) to assess the association between these SNPs and incident GCC (n = 90) and ESCC (n = 131). IL8, IL8RA, and IL8RB SNPs were analyzed using a multiplex assay system, haplotypes were constructed, and risks were estimated using Cox proportional hazards models. The homozygous variants of IL8 −251 and +396 were associated with 2-fold increased relative risks for GCC, but the highest risk observed was for the AGT/AGC haplotype of IL8 −251/+396/+781 (relative risk, 4.14; 95% confidence interval, 1.31-13.1). Variation within IL8 was not associated with ESCC. Few subjects had variation at the IL8RA SNP and no significant associations were observed for IL8RB SNPs or haplotypes with either GCC or ESCC. We conclude that variation in IL8 seems to increase the risk for GCC but not ESCC in this high-risk population. These variants could confer an altered IL8 expression pattern or interact with environmental factors to increase the risk for inflammation and GCC.
Uptake of Offer to Receive Genetic Information about BRCA1 and BRCA2 Mutations in an Australian Population-Based Study
Authors: Keogh Louise A. , Southey Melissa C. , Maskiell Judi , Young Mary-Anne , Gaff Clara L. , Kirk Judy , Tucker Katherine M. , Rosenthal Doreen , McCredie Margaret R.E. , Giles Graham G. , Hopper John L. 
Published: June 2022

Abstract
Research on the utilization of genetic testing services for mutations in BRCA1 and BRCA2 has focused on women with a strong family history of breast and ovarian cancer. We conducted a population-based case-control-family study of Australian women diagnosed with invasive breast cancer before age 40 years, unselected for family history, and tested for germ line mutations in BRCA1 and BRCA2. Case subjects found to carry a deleterious mutation and their relatives who had given a research blood sample were informed by mail that the study had identified “genetic information” and were offered the opportunity to learn more. Those interested were referred to a government-funded family cancer clinic. Of 94 subjects who received the letter, 3 (3%) did not respond and 38 (40%) declined to learn their result (16 declined the referral, 10 accepted but did not attend a clinic, and 12 attended a clinic but declined testing), and 12 (13%) remain “on hold.” The remaining 41 (44%) chose to learn their result (3 of whom already knew their mutation status). There was no evidence that the decision to learn of mutation status depended on age, gender, family history, or having been diagnosed with breast cancer. Of 19 families with more than one participant, in 11 (58%) there was discordance between relatives in receiving genetic results. Although in Australia genetic testing is offered free of charge and insurance issues are not a major consideration, we found considerable reluctance, indecision, and unexplained variability both between and within case families in the desire to know their mutation status.
Aspirin and Other Nonsteroidal Anti-inflammatory Drugs and Breast Cancer Incidence in a Large U.S. Cohort
Authors: Jacobs Eric J. , Thun Michael J. , Connell Cari J. , Rodriguez Carmen , Henley S. Jane , Feigelson Heather S. , Patel Alpa V. , Flanders W. Dana , Calle Eugenia E. 
Published: June 2022

Abstract
Use of nonsteroidal anti-inflammatory drugs (NSAIDs), particularly aspirin, has consistently been associated with reduced risk of breast cancer in case-control studies. However, results from prospective studies have been less consistent. We examined the association between NSAID use and breast cancer incidence, adjusting for multiple breast cancer risk factors among 77,413 women in the Cancer Prevention Study II Nutrition Cohort. During follow-up from 1992 to 2001, we observed 3,008 cases of incident breast cancer. Information on NSAID use was obtained from a questionnaire completed at enrollment in 1992 or 1993 and was updated using follow-up questionnaires in 1997 and 1999. NSAID use was modeled using time-dependent variables to update exposure status. Neither current total NSAID use (aspirin and other NSAIDs combined) nor current aspirin use were associated with breast cancer incidence even at relatively high levels of use [rate ratio (RR), 1.07; 95% confidence interval (95% CI), 0.96-1.21 for ≥60 NSAID pills per month compared with no reported use of NSAIDs; RR, 1.01; 95% CI, 0.84-1.20 for ≥60 aspirin per month compared with no reported use of aspirin]. Even long-duration regular use (≥30 pills per month for ≥5 years) was not associated with breast cancer incidence (RR, 1.05; 95% CI, 0.88-1.26 for total NSAIDs; RR, 0.88; 95% CI, 0.69-1.12 for aspirin). Although we cannot exclude a small reduction in breast cancer risk associated with NSAID use, the results of this study provide evidence against a large reduction in risk.