bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Alcohol and Menstrual Cycle on Insulin-like Growth Factor-I and Insulin-like Growth Factor Binding Protein-3
Authors: Lavigne Jackie A. , Wimbrow Heather H. , Clevidence Beverly A. , Albert Paul S. , Reichman Marsha E. , Campbell William S. , Barrett J. Carl , Hursting Stephen D. , Judd Joseph T. , Taylor Philip R.
Published: June 2022

Alcohol ingestion and insulin-like growth factor-I (IGF-I) have been associated with increased breast cancer risk, the latter primarily in premenopausal women. We investigated whether alcohol ingestion altered IGF-I or its major binding protein (BP), IGFBP-3, in a controlled feeding study in premenopausal women. We also determined whether IGF-I or IGFBP-3 was affected by menstrual cycle phase. Serum was collected from 31 individuals who were randomly assigned to consume either 0 or 30 g (two drinks) of alcohol daily for three menstrual cycles and who then crossed over to the other alcohol level for three cycles. All calories were provided and weight was maintained during the study. For both alcohol levels, serum was collected during the final cycle at early follicular, periovulatory, and luteal phases. Relative to the follicular phase, IGF-I levels increased by 3.3% and 7.6% in the periovulatory and luteal phases, respectively (P for trend = 0.004). Although alcohol ingestion did not affect this increase, it significantly reduced IGF-I concentrations at all phases (9.5%; P < 0.001), whereas IGFBP-3 was unaffected by either menstrual phase or alcohol. This is the first controlled diet study to show that alcohol decreases serum IGF-I in premenopausal women and that IGF-I significantly increases over the course of the menstrual cycle whether or not alcohol is present.
MTHFR Polymorphisms and Risk of Chronic Lymphocytic Leukemia
Authors: Rudd Matthew F. , Sellick Gabrielle S. , Allinson Ruth , Matutes Estella , Catovsky Daniel , Houlston Richard S.
Published: June 2022

Folate availability is critical for DNA integrity, required for the transfer of methyl groups in the biosynthesis of thymidilate. Reduction of 5,10-methylenetetrahydrofolate, a donor for methylating dUMP to dTMP in DNA synthesis, to 5-methyltetrahydrofolate, the primary methyl donor for methionine synthesis, is catalyzed by 5,10-methylenetetrahydrofolate reductase (MTHFR). The MTHFR polymorphisms C677T and A1298C have been shown in some studies to alter the risk of a range of different malignancies. We evaluated the role of the C677T and A1298C polymorphisms on chronic lymphocytic leukemia (CLL) risk by genotyping 832 patients and 886 healthy controls. The odds ratio of CLL associated with 677CT and 677TT genotypes were 1.02 [95% confidence interval (95% CI), 0.83-1.24] and 0.90 (95% CI, 0.66-1.24), respectively. The odds ratio of CLL associated with 1298AC and 1298CC genotypes were 0.97 (95% CI, 0.79-1.18) and 0.88 (95% CI, 0.62-1.24), respectively. This data indicate that the MTHFR polymorphisms C677T and A1298C do not significantly contribute to an inherited genetic susceptibility to CLL.
Antioxidant Vitamin Supplementation Reduces Benzo(a)pyrene-DNA Adducts and Potential Cancer Risk in Female Smokers
Authors: Mooney LaVerne A. , Madsen Ann M. , Tang Deliang , Orjuela Manuela A. , Tsai Wei-Yann , Garduno Elizabeth R. , Perera Frederica P.
Published: June 2022

Background: Elevated benzo(a)pyrene [B(a)P]-DNA adducts have been associated with 3-fold increased risk of lung cancer in current smokers. We assessed the chemopreventive effects of antioxidant supplementation using B(a)P-DNA adducts in leukocytes as an intermediate cancer risk marker.

Methods: Subjects were randomized to a double-blinded placebo-controlled clinical trial of antioxidant vitamin supplementation [500 mg vitamin C and 400 IU vitamin E (dl-α-tocopherol) daily] or placebo. Smokers with ≥10 cigarettes per day and serum cotinine ≥25 ng/mL were eligible for the study. B(a)P-DNA adduct level was the outcome. The randomization was stratified by gender and cigarettes per day (≤20 or >20). Smoking habits and blood samples were collected every 3 months during the 15-month treatment period. Samples were analyzed for B(a)P-DNA adducts (high-performance liquid chromatography), plasma cotinine, vitamin levels, and GSTM1 genotype. The intent-to-treat model adjusted for B(a)P-DNA and cotinine at randomization.

Results: Overall and among men, there was no effect of treatment on B(a)P-DNA adduct levels. Among treated women, B(a)P-DNA adducts decreased by 31% compared with women on placebo (P = 0.03). Among treated women with the GSTM1 genotype, there was a 43% decrease in adducts (P = 0.04).

Conclusion: Our primary hypothesis that the mean level of smoking-related B(a)P-DNA adducts would be lower in all subjects in the vitamin treatment group compared with all placebo-treated subjects was not substantiated. However, oursecondary gender-specific analysis found a significant reduction in B(a)P-DNA adducts in women with vitamin treatment, suggesting that antioxidant supplementation maymitigate some of the procarcinogenic effects of exposuretoB(a)P. The effect in GSTM1-null women suggeststhat certain subgroups may derive more benefit fromsupplementation. Although the results of this trial showthe potential chemopreventive role of antioxidants, thebest way for smokers to reduce their cancer risk remains smoking cessation.
Common BRCA2 Variants and Modification of Breast and Ovarian Cancer Risk in BRCA1 Mutation Carriers
Authors: Hughes David J. , Ginolhac Sophie M. , Coupier Isabelle , Corbex Marilys , Bressac-de-Paillerets Brigitte , Chompret Agnès , Bignon Yves-Jean , Uhrhammer Nancy , Lasset Christine , Giraud Sophie , Hardouin Agnès , Berthet Pascaline , Peyrat Jean-Philippe , Fournier Joelle , Nogues Catherine , Lidereau Rosette , Muller Danièle , Fricker Jean-Pierre , Longy Michel , Toulas Christine , Guimbaud Rosine , Maugard Christine , Olschwang Sylviane , Yannoukakos Drakoulis , Durocher Francine , Moisan Anne-Marie , Simard Jacques , Mazoyer Sylvie , Lynch Henry T. , Szabo Csilla , Lenoir Gilbert M. , Goldgar David E. , Stoppa-Lyonnet Dominique , Sinilnikova Olga M.
Published: June 2022

The HH genotype of the nonconservative amino acid substitution polymorphism N372H in the BRCA2 gene was reported to be associated with a 1.3- to 1.5-fold increase in risk of both breast and ovarian cancer. As these studies concerned sporadic cancer cases, we investigated whether N372H and another common variant located in the 5′-untranslated region (203G > A) of the BRCA2 gene modify breast or ovarian cancer risk in BRCA1 mutation carriers. The study includes 778 women carrying a BRCA1 germ-line mutation belonging to 403 families. The two BRCA2 variants were analyzed by the TaqMan allelic discrimination technique. Genotypes were analyzed by disease-free survival analysis using a Cox proportional hazards model. We found no evidence of a significant modification of breast cancer penetrance in BRCA1 mutation carriers by either polymorphism. In respect of ovarian cancer risk, we also saw no effect with the N372H variant but we did observe a borderline association with the 5′-untranslated region 203A allele (hazard ratio, 1.43; CI, 1.01-2.00). In contrast to the result of Healey et al. on newborn females and adult female controls, we found no departure from Hardy-Weinberg equilibrium in the distribution of N372H alleles for our female BRCA1 carriers. We conclude that if these single-nucleotide polymorphisms do modify the risk of cancer in BRCA1 mutation carriers, their effects are not significantly larger than that of N372H previously observed in the general population.
Serum Fructosamine and Subsequent Breast Cancer Risk: A Nested Case-Control Study in the ORDET Prospective Cohort Study
Authors: Platek Mary , Krogh Vittorio , Micheli Andrea , Browne Richard , Meneghini Elisabetta , Sieri Sabina , Schünemann Holger J. , Pala Valeria , Barba Maddalena , Wilding Gregory E. , Berrino Franco , Muti Paola
Published: June 2022

There is evidence that abnormal glucose metabolism may contribute to the risk of breast cancer. The measurement of markers of glucose metabolism could help to identify women at risk for breast cancer. Serum fructosamine is one such marker. In this study, we investigated whether prediagnostic serum fructosamine was associated with breast cancer. Between 1987 and 1992, 10,786 women ages 35 to 69 were recruited in Italy for a prospective study. Women with a history of cancer or on hormone therapy were excluded at baseline. Blood samples were collected after 12 hours fasting from all participants at recruitment. After 5.5 years of follow-up, 144 breast cancer cases were identified and four matched controls were selected from the cohort; serum fructosamine levels were measured in both groups at baseline. Adjusted odds ratios (OR) for the highest tertile of serum fructosamine compared to the lowest was 1.60 [95% confidence interval (CI), 0.95-2.73]. In premenopausal women, the OR was 1.58 (95% CI, 0.76-3.40) and in postmenopausal women, the OR was 1.60 (95% CI, 0.76-3.48). Serum fructosamine levels tended to be positively associated with breast cancer risk independent of menopausal status.
Germ-Cell Testicular Cancer in Offspring of Finnish Immigrants to Sweden
Authors: Montgomery Scott M. , Granath Fredrik , Ehlin Anna , Sparén Pär , Ekbom Anders
Published: June 2022

Variation in testicular cancer incidence can be used to assist in identification of risks. Finland has a significantly lower germ-cell testicular cancer risk than Sweden. Finns who immigrate to Sweden maintain their lower risk irrespective of age at immigration. We investigated difference in risk between Finland and Sweden by examining germ-cell testicular cancer incidence in males born in Sweden to Finnish immigrant parents. Swedish general population registers were used to identify 11,662 males born in Sweden where both Finnish parents immigrated to Sweden from Finland from 1969 or afterward. All of these offspring were at least 15 years old by final follow-up in 2001. Some six offspring (all diagnosed between ages 20 and 24 years) had a diagnosis of germ-cell testicular cancer. Comparison with the Swedish population rate produced standardized incidence ratios [SIR (95% confidence interval)] of 0.85 (0.31-1.84) for all the men and 1.75 (0.64-3.81) for the 20- to 24-year age group. SIRs calculated using the Finnish population rates produced an overall SIR (95% confidence interval) of 1.11 (0.41-2.41) and 2.95 (1.08-6.42) for the 20- to 24-year age group. Although the substantially reduced risk of testicular cancer previously observed in Finnish immigrant to Sweden was not found, this study had insufficient statistical power to conclude that environmental exposures explain the difference in germ-cell testicular cancer risk between Finland and Sweden.
Metabolic and Hormonal Profiles: HDL Cholesterol as a Plausible Biomarker of Breast Cancer Risk. The Norwegian EBBA Study
Authors: Furberg Anne-Sofie , Jasienska Grazyna , Bjurstam Nils , Torjesen Peter A. , Emaus Aina , Lipson Susan F. , Ellison Peter T. , Thune Inger
Published: June 2022

Low serum high-density lipoprotein cholesterol (HDL-C) is an important component of the metabolic syndrome and has recently been related to increased breast cancer risk in overweight and obese women. We therefore questioned whether serum HDL-C might be a biologically sound marker of breast cancer risk. We obtained cross-sectional data among 206 healthy women ages 25 to 35 years who participated in the Norwegian EBBA study. We included salivary ovarian steroid concentrations assessed by daily samples throughout one entire menstrual cycle, metabolic profile with measures of adiposity [body mass index (BMI) and truncal fat percentage], serum concentrations of lipids and hormones (insulin, leptin, testosterone, dehydroepiandrostendione sulfate, insulin-like growth factor-I, and its principal binding protein), and mammographic parenchymal pattern. We examined how components of the metabolic syndrome, including low serum HDL-C, were related to levels of hormones, and free estradiol concentration in particular, and studied predictors of mammographic parenchymal patterns in regression models. In women with BMI ≥ 23.6 kg/m2 (median), overall average salivary estradiol concentration dropped by 2.4 pmol/L (0.7 pg/mL; 13.2% change in mean for the total population) by each 0.33 mmol/L (12.8 mg/dl; 1SD) increase in serum HDL-C (P = 0.03; Pinteraction = 0.03). A subgroup of women characterized by both relatively high BMI (≥23.6 kg/m2) and high serum LDL-C/HDL-C ratio (≥ 2.08; 75 percentile) had substantially higher levels of salivary estradiol by cycle day than other women (P = 0.001). BMI was the strongest predictor of overall average estradiol with a direct relationship (P< 0.001). Serum HDL-C was inversely related to serum leptin, insulin, and dehydroepiandrostendione sulfate (P < 0.001, P < 0.01, and P < 0.05, respectively). There was a direct relationship between breast density and healthy metabolic profiles (low BMI, high serum HDL-C; P < 0.001) and salivary progesterone concentrations (P < 0.05). Our findings support the hypothesis that low serum HDL-C might reflect an unfavorable hormonal profile with, in particular, increased levels of estrogens and gives further clues to biomarkers of breast cancer risk especially in overweight and obese women.
Pap Screening in a U.S. Health Plan
Authors: Insinga Ralph P. , Glass Andrew G. , Rush Brenda B.
Published: June 2022

The U.S. Preventive Services Task Force recommends cervical cancer screening begin with the onset of sexual activity and be repeated at least every 3 years until age 65. Previous studies examining the annual utilization and frequency of Pap screening have relied on patient self-report, found to be less reliable than medical records and administrative data. We estimate the age-specific rate and frequency of Pap screening in a U.S. health plan using 1998–2002 administrative data on 150,052 female enrollees within the Kaiser Permanente Northwest health plan, Portland, OR. We analyze the age-specific rate of cervical and vaginal Pap screening and age-specific proportion of routinely screened women receiving cervical screening at various yearly intervals. Of the enrolled women, 31.2% received a Pap smear in 1998, with utilization highest for ages 25–29 (62.4%). Among routinely screened women, 36% were estimated to receive annual cervical smears, versus 22% biennial, 13% triennial, and 29% less frequent screening. Less frequent screening was observed with increasing age. These are the first age-specific estimates of Pap screening frequency and annual utilization in a general healthcare setting, derived from administrative data, rather than self-report. Overall Pap utilization was lower than found in national surveys based on self-report. Despite limited evidence of benefit from more frequent screening, a substantially higher proportion of women was found to receive annual rather than either biennial or triennial screening. Sporadic screening was also more prevalent than expected based on prior self-reported data. Further opportunities exist for improving screening adherence, even within traditionally less vulnerable populations.
DNA Stability and Serum Selenium Levels in a High-Risk Group for Prostate Cancer
Authors: Karunasinghe Nishi , Ryan Jacqueline , Tuckey John , Masters Jonathan , Jamieson Michael , Clarke Larry C. , Marshall James R. , Ferguson Lynnette R.
Published: June 2022

The essential micronutrient, selenium, is at low levels in the New Zealand diet. Selenium is a component of a number of proteins involved in the maintenance of genomic stability, and recommended daily allowances (RDA) are set on saturation levels for glutathione peroxidase (GPx), a key enzyme in surveillance against oxidative stress. It has been assumed but not proven that this level will be adequate for other key selenoenzymes. The “Negative Biopsy Trial” identifies a group of New Zealand individuals at high risk of prostate cancer, whose serum selenium levels will be monitored and who will be supplemented with a yeast-based tablet, with or without selenium, over an extended time. Access to patients on this trial provides the opportunity to ask the more generic question as to whether selenium levels in this population are adequate to maintain genomic stability. The single cell gel electrophoresis (comet) assay was used to study DNA damage in blood leukocytes harvested from these volunteers. Average serum selenium levels before randomization was 97.8 ± 16.6 ng/ml, low by international standards. For the half of the population below this mean value, lower serum selenium levels showed a statistically significant inverse relationship (P = 0.02) with overall accumulated DNA damage. Although other interpretations cannot be excluded, the data suggest that the selenium intake in half of this population is marginal for adequate repair of DNA damage, increasing susceptibility to cancer and other degenerative diseases. It also raises the question as to whether glutathione peroxidase saturation levels are appropriate indicators of the optimal selenium levels for a given population.
A Prospective Study of Smoking and Risk of Breast Cancer in Young Adult Women
Authors: Al-Delaimy Wael K. , Cho Eunyoung , Chen Wendy Y. , Colditz Graham , Willet Walter C.
Published: June 2022

Objective: To investigate the association between smoking and invasive breast cancers characterized by their estrogen receptor status in a large prospective study of mainly premenopausal women. Method: 112,844 women aged 25–42 years in 1989 were followed 10 years; questionnaire information on medical illnesses and risk factors was collected biennially and information on diet was collected in 1991 and 1995. During this period of follow-up (1,077,536 person-years), 1009 incident breast cancer cases were documented. Results: In the multivariate-adjusted models, smoking status was not significantly related to overall breast cancer risk: compared with never smokers, the relative risks (RRs) were 1.18 [95% confidence interval (CI) 1.02–1.36] for past smokers and 1.12 (95% CI 0.92–1.37) for current smokers. Increasing duration of smoking before the first pregnancy was associated with a greater risk of breast cancer, although little increase was seen in the highest category: compared with never smokers, RRs were 1.42 (95% CI 1.10–1.83) for 15–19 years of smoking and 1.10 (95% CI 0.80–1.52) for ≥20 years of smoking (P for trend = 0.01). Smoking was related most strongly to the risk of estrogen receptor-positive breast cancers. For women who had smoked for ≥20 years, the RR of estrogen receptor-positive cancer was 1.37 (95% CI 1.07–1.74) and the RR of estrogen receptor-negative cancer was 1.04 (95% CI 0.71–1.53). For smoking before age 15, the RRs were 1.49 (95% CI 1.03–2.17) for estrogen receptor-positive cancer and 1.19 (95% CI 0.69–2.08) for estrogen receptor-negative cancer. Conclusion: Our results suggest that longer duration of smoking may be related to the risk of estrogen receptor-positive breast cancer but possibly less so for estrogen receptor-negative breast cancer.
Hepatitis C Virus and Risk of Non-Hodgkin Lymphoma: A Population-Based Case-Control Study among Connecticut Women
Authors: Morton Lindsay McOmber , Engels Eric A. , Holford Theodore R. , Leaderer Brian , Zhang Yawei , Zahm Shelia Hoar , Boyle Peter , Zhang Bing , Flynn Stuart , Tallini Giovanni , Owens Patricia H. , Zheng Tongzhang
Published: June 2022

Objective: Previous epidemiologic studies of hepatitis C virus (HCV) infection and B-cell non-Hodgkin lymphoma (B-NHL) have yielded conflicting results, perhaps due to differences in the classification of B-NHL and the choice of non-population-based control groups that may not reflect the background population prevalence of HCV. To further investigate the link between HCV and NHL, we conducted HCV testing on serum samples of 998 women (464 cases; 534 controls) from a population-based case-control study of women in Connecticut. Methods: Serum samples were screened for HCV antibodies using an enzyme immunoassay; positive samples were confirmed by additional testing for HCV antibodies and for serum HCV RNA. Results: Approximately 2% (8 of 464) of cases and 1% (5 of 534) of controls tested positive for HCV. The risk of NHL associated with HCV infection appeared to be concentrated among B-cell lymphomas [odds ratio (OR) 2.0; 95% confidence interval (CI) 0.6, 8.2], particularly among follicular lymphomas (OR 4.1, 95% CI 0.8, 19.4). Conclusion: The primary strength of this study is our use of a population-based study design, although the low prevalence of HCV among women in Connecticut resulted in wide CIs for the estimated association between HCV and B-NHL subtypes. Our study suggests that HCV may be associated with increased risk of development of B-NHL, and that this risk may vary by B-NHL subtype among women. Due to the relatively low prevalence of HCV in our study population and the scarcity of population-based epidemiological research on this subject, our study highlights the need for additional large, population-based studies of the role of HCV in the etiology of B-NHL.
Glutathione-S-Transferase Variants and Adult Glioma
Authors: Wrensch Margaret , Kelsey Karl T. , Liu Mei , Miike Rei , Moghadassi Michelle , Aldape Kenneth , McMillan Alex , Wiencke John K.
Published: June 2022

Introduction: Conflicting findings have been reported for associations of primary brain tumors and constitutive polymorphisms in glutathione-S-transferases (GSTs). Methods: We genotyped population-based cases ascertained through rapid case ascertainment and controls identified through random-digit dialing in the San Francisco Bay Area between 1991–1994 (series 1) and 1997–2000 (series 2) for homozygous deletion or presence of GSTM1 (μ) and GSTT1 (𝛉) genes and for two variants in GSTP (π i.e., I105V and A114V). A single neuropathologist for each series determined histological type. Blood or buccal swabs were obtained from about 53.8% of cases and 64.6% of controls. Case-control genotype frequencies were compared overall and by histological type and by age group (≤40, 41–60, and >60), gender, and series. Results: Among whites, 367 cases (179 glioblastoma, 62 other astrocytoma, 94 oligodendroglioma or oligoastrocytoma, and 32 other histologies) and 428 controls were genotyped for all four polymorphisms. Multivariate logistic models including the four GST loci, age, gender (except in gender-specific models), and series showed no significant case-control differences for GST genotypes. Among cases over age 60, prevalence of GSTP I105V Val/Val was 6.4% of 108 cases versus 15% of 176 controls [odds ratio (OR) 0.38; 95% confidence interval (CI) 0.15–0.93; P = 0.03]. GSTT1 deletion was nearly significantly more common among glioblastoma cases with tumor p53 mutation than for those whose tumors did not have p53 mutation (OR 2.8; 95% CI 0.93–8.4; P = 0.07). Conclusions: There is little evidence for associations of GST variants with major glioma histological subtypes, but GST polymorphisms might influence certain molecular subtypes or progression.
Insulin-Like Growth Factor-I, IGF Binding Protein-3, and Breast Cancer in Young Women: A Comparison of Risk Estimates Using Different Peptide Assays
Authors: Rinaldi Sabina , Kaaks Rudolf , Zeleniuch-Jacquotte Anne , Arslan Alan A. , Shore Roy E. , Koenig Karen L. , Dossus Laure , Riboli Elio , Stattin Pär , Lukanova Annekatrin , Toniolo Paolo
Published: June 2022

Circulating insulin-like growth factor-I (IGF-I) and its major binding protein IGF binding protein-3 (IGFBP-3) have been associated with increased risk of premenopausal breast cancer, although risk estimates varied broadly. An extension of a case-control study (138 cases, 259 matched controls) on IGF-I and breast cancer in premenopausal women nested in the New York University Women's Health Study cohort offered the opportunity to address the hypothesis that such variability may have been the result of variations in the ability of different IGFBP-3 assays to specifically measure intact/functional forms of the protein. IGF-I and IGFBP-3 had originally been measured using in-house RIAs. These measurements were repeated using commercially available ELISAs [Diagnostic System Laboratories (DSL), Webster, Texas], and a third ELISA with greater specificity for active forms for IGFBP-3. Pearson's correlations between IGF-I concentrations in the original study and DSL ELISA were very high [r = 0.92; 95% CI, 0.90-0.94]. Correlations with DSL ELISA were much lower for IGFBP-3 (r = 0.58; 0.49-0.66) and even lower still with the assay for functional IGFBP-3 (r = 0.33; 0.20-0.44). IGF-I and IGFBP-3 measurements by the DSL ELISA methods showed statistically significant relationships with risk. The odds ratios (OR) for top versus bottom quartiles were 1.93 (1.00-3.72; P = 0.02) and 2.03 (1.09-3.76; P = 0.02), respectively, in agreement with the original observations. In contrast, measurements of functional IGFBP-3 tended to be unrelated to risk [ORs for the top versus bottom quartile, 0.97 (0.44-2.11)]. The association with IGF-I became substantially weaker and lost statistical significance after adjustment for IGFBP-3 using DSL ELISA, but became considerably stronger when adjusting for the functional IGFBP-3 measurements [OR = 2.43 (1.21-4.90); P = 0.005], or when considering the molar ratio of IGF-I to IGFBP-3 [OR = 2.37 (1.13-5.00); P = 0.02]. These results are consistent with an association of breast cancer risk in young women with elevated IGF-I and IGFBP-3, and show that for IGFBP-3, the strength of such an association could vary substantially depending on the assay used.
High Incidence of Nasopharyngeal Carcinoma in Native People of Sarawak, Borneo Island
Authors: Devi Beena C. R. , Pisani Paola , Tang Tieng Swee , Parkin D. Maxwell
Published: June 2022

Nasopharyngeal cancer (NPC) is generally a rare malignancy with a few well-known exceptions, notably South-East China. In this article, we describe evidence of a high risk of NPC in the population of Sarawak State, Malaysia, and particularly in one native ethnic group. Sarawak State is one of the two provinces of Malaysia located on the island of Borneo. The native population (71.6%) includes the Iban, Malay, Bidayuh, Melanau, and diverse smaller ethnic groups. The Chinese are the largest nonindigenous group (27.5%). We identified 392 newly diagnosed cases (292 males and 100 females) of NPC in 1996–1998 in Malaysian citizens, permanent residents of Sarawak. Age-standardized rates by sex and ethnic group were compared with the highest rates in the world. The age-adjusted rate (ASR) in Sarawak residents was 13.5/100,000 [95% confidence interval (CI) 12.2–15.0] and 6.2/100,000 (95% CI 5.7–6.7) in males and females, respectively. The risk in the Bidayuh people was 2.3-fold (M) and 1.9-fold (F) higher than the Sarawak average, and about 50% higher than that in Hong Kong—the highest recorded by any population-based registry for the same period. Local dietary habits, environmental exposures, and genetic susceptibility deserve investigation in this population.
Dietary Fish Intake and Risk of Leukaemia, Multiple Myeloma, and Non-Hodgkin Lymphoma
Authors: Fritschi Lin , Ambrosini Gina L. , Kliewer Erich V. , Johnson Kenneth C. ,   Canadian Cancer Registries Epidemiologic Research Group
Published: June 2022

This study aimed to determine whether fish intake was protective against leukemia, multiple myeloma, and non-Hodgkin lymphoma (NHL), and if our previous finding of a protective effect of fish-related occupations on the risk of these diseases was due to dietary intake of fish. We used data from a population-based case-control study undertaken in Canada in 1994–1998. Dietary information was available for 919 leukemia cases, 287 myeloma cases, 1418 NHL cases, and 4202 controls. The risk of each of the three cancers was determined using multiple logistic regression analysis according to quartiles of weekly fresh fish intake, percentage of total energy intake from fresh fish, and percentage of total fat intake from fresh fish. After adjusting for age, sex, smoking, BMI, and proxy status, people who consumed greater proportions of their total energy intake from fresh fish had a significantly lower risk of each of the three types of cancer, and there was a significant dose-response for risk of leukemia and NHL. Those in the highest quartile for percentage of fat intake from fish were at lowest risk: leukemia odds ratio (OR) 0.72, 95% confidence interval (CI) 0.58–0.89; multiple myeloma OR 0.64, 95% CI 0.45–0.90; NHL OR 0.71, 95% CI 0.60–0.85; and all LH cancers combined OR 0.70, 95% CI 0.61–0.81. The protective effect previously observed for working with fish on the risk of leukemia and lymphoma was independent of fish intake. These findings suggest that a diet high in fish may be protective against lymphohematopoietic cancers and confirm the reduced risk among fish workers.
Modifying Attributions of Colorectal Cancer Risk
Authors: Lipkus Isaac M. , Skinner Celette Sugg , Green La Sonya G. , Dement John , Samsa Gregory P. , Ransohoff David
Published: June 2022

We report how a four-group risk communication intervention targeted to individuals in the carpentry trade affected their perceived causes (i.e., attributions) for increased colorectal cancer (CRC) risk. The intervention varied the amount of information presented on CRC risk factors and whether participants received tailored feedback on their risk factors. In baseline and 3-month follow-up telephone surveys, carpenters (N = 860) reported their perceived absolute and comparative CRC risks, perceived causes for increased CRC risk, and knowledge of CRC risk factors. At follow-up, neither the type or amount of information provided, nor the use of tailoring, appreciably and consistently affected whether participants mentioned their specific risk factor (e.g., lifestyle, occupational) emphasized in their intervention information. Furthermore, attributions did not affect CRC risk perceptions. These results suggest that participants do not integrate sufficiently CRC risk factor information into their conceptualizations of CRC risk, and that more effective methods are needed to contextualize risk factors information to achieve the goal of modifying CRC risk perceptions.
No Evidence of an Association of JC Virus and Colon Neoplasia
Authors: Newcomb Polly A. , Bush Angela C. , Stoner Gerald L. , Lampe Johanna W. , Potter John D. , Bigler Jeannette
Published: June 2022

JC virus (JCV) is an ubiquitous human polyomavirus that frequently resides in the kidneys of healthy individuals and is excreted in the urine of a large proportion of the adult population. Polyomaviruses are associated with disease largely in immunocompromised individuals (progressive multifocal leukoencephalopathy). Colorectal cancers can show chromosome instability and it was hypothesized that JCV may account for some of this instability. We screened urine from 45 healthy donors and 233 colorectal cancer/normal tissue pairs for the presence of JCV sequences using a Taqman assay. This assay could detect 1 virus genome in 10 human genomes. In the urine samples, we found an infection rate of approximately 70%. The JCV isolates in these samples could be categorized into four JCV types (2B, 4, 7, and 8), none of which had a rearranged regulatory region. Among the colon tissues, one normal tissue (<0.5%) and none of the matched tumors tested positive for JCV. There is no evidence in these data to indicate that JCV is the cause of genetic instability in colorectal cancer.
Adipose Organochlorine Concentrations and Risk of Breast Cancer Among Postmenopausal Danish Women
Authors: Raaschou-Nielsen Ole , Pavuk Marian , LeBlanc Alain , Dumas Pierre , Philippe Weber Jean , Olsen Anja , Tjønneland Anne , Overvad Kim , Olsen Jørgen H.
Published: June 2022

Objective: Exposure to environmental organochlorines has been examined as a potential risk factor for human breast cancer with mixed results. Our purpose was to examine associations between organochlorines and the development of breast cancer in a large prospective study using stored adipose tissue. Methods: We conducted a nested case-control study of 409 postmenopausal women who developed breast cancer and 409 controls selected from the 29,875 women enrolled in the Danish Diet, Cancer, and Health cohort between 1993 and 1997. We measured concentrations of 14 pesticides and 18 polychlorinated biphenyls in adipose tissue, collected upon enrollment, and estimated relative risk (RR) of breast cancer using conditional logistic regression. Results: The results showed no higher risk of breast cancer among women with higher levels of any pesticides or polychlorinated biphenyls; the RR associated with the upper quartile of 1,1-dichloro-2, 2-bis(p-chlorophenyl)ethylene concentration was 0.7 [95% confidence interval (95% CI), 0.5-1.2] contrasting the lower quartile, and for the sum of polychlorinated biphenyls the similar risk was 1.1 (95% CI, 0.7-1.7). We observed a pattern of substantially lower risk of estrogen receptor–negative breast cancer in association with higher levels of most of the pesticides and polychlorinated biphenyls; the RR for the higher quartile of 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene was 0.1 (95% CI, 0.0-0.5) and for the sum of polychlorinated biphenyls it was 0.3 (95% CI, 0.1-0.9). Conclusion: The results do not support that higher organochlorine body levels increase the risk of breast cancer in postmenopausal women. The interpretation of the inverse association for estrogen receptor–negative breast cancer is currently unclear.
Epstein-Barr Virus and Breast Cancer: State of the Evidence for Viral Carcinogenesis
Authors: Glaser Sally L. , Hsu Joe L. , Gulley Margaret L.
Published: June 2022

As the etiology and progression of breast cancer remain incompletely understood, novel routes of disease pathogenesis are important to consider. Viral pathogens have not been much explored, but recent interest has focused on Epstein-Barr virus (EBV). Studies of an association of this ubiquitous herpesvirus with breast cancer have had notably inconsistent results, marked by varying EBV presence (from 0% to 50% of tumors) and the absence of certain viral characteristics found in other EBV-related malignancies. The research has been plagued by the technical challenges of localizing EBV to tumor cells and by a tendency to overlook epidemiological cofactors, shown in all other EBV-related cancers to impact the EBV association. Breast cancer studies to date have used several viral detection methods of varying or uncertain sensitivity and specificity; most have involved small and/or poorly characterized case series and paid insufficient attention to epidemiological cofactors relevant to breast cancer and to EBV-related malignancies. Given these limitations and the established complexity of the connection of EBV with other cancers, a definitive judgment regarding the presence of this virus in breast cancer cannot yet be rendered. Recent advances in laboratory methodologies should help overcome the challenges of EBV detection in breast cancers. Further research is warranted, given the potential for an EBV association to inform not only breast cancer etiology but also early detection, treatment, and prevention.
A Prospective Study of Breast Cancer Risk Using Routine Mammographic Breast Density Measurements
Authors: Vacek Pamela M. , Geller Berta M.
Published: June 2022

Mammographic breast density is a major risk factor for breast cancer but estimates of the relative risk associated with differing density patterns have varied widely. It is also unclear how menopausal status influences this association and to what extent the effects of density are due to its correlation with other risk factors. Most recent investigations of breast density have been case-control studies, which provide indirect estimates of relative risk. We have prospectively followed 61,844 women for an average of 3.1 years to directly estimate risk among women in the four mammographic breast density categories defined by the American College of Radiology's Breast Imaging Reporting and Data System (BI-RADS). The study was population-based and used density assessments routinely made by community radiologists. Cox regression was used to obtain age-adjusted relative risk estimates and to control for other risk factors. Risk increased with density and the risk associated with extremely dense breasts, relative to entirely fatty breasts, was 4.6 (95% confidence interval, 1.7–12.6) for premenopausal women and 3.9 (95% confidence interval, 2.6–5.8) for postmenopausal women. Estimates for pre- and postmenopausal women did not differ significantly. Although breast density was significantly related to body mass index, age at first childbirth, and postmenopausal hormone use (P < 0.001), adjustment for these variables only slightly altered the relative risk estimates. Our results correspond well to those from case-control studies using more quantitative measures of mammographic breast density and suggest that routine Breast Imaging Reporting and Data System density measurements may be useful in models for assessing breast cancer risk in individual women.
What Factors Are Associated with Diagnostic Follow-Up after Abnormal Mammograms? Findings from a U.S. National Survey
Authors: Yabroff K. Robin , Breen Nancy , Vernon Sally W. , Meissner Helen I. , Freedman Andrew N. , Ballard-Barbash Rachel
Published: June 2022

The purpose of this study was to identify factors associated with diagnostic follow-up after an abnormal mammogram in a national sample of women in the U.S. The sample was selected from the year 2000 National Health Interview Survey and included 1901 women aged 30 and above who reported ever having an abnormal mammogram. The outcome measure was receipt of at least some diagnostic follow-up after an abnormal mammogram. Bivariate and multivariate logistic regression analyses were used to explore the associations between sociodemographic characteristics, general health and health behaviors, cancer risk and risk perceptions, and health care utilization characteristics and follow-up. Approximately 9% of women who reported ever having abnormal mammograms reported not completing any additional diagnostic follow-up. Controlling for all other factors, women with less than a high school education were less likely to report follow-up after an abnormal mammogram than were women who had at least completed college (odds ratio = 0.56; 95% confidence interval: 0.32, 0.98). Younger women and women in poorer health were also less likely to report follow-up. Women who perceived a high versus low level of cancer in their family were more likely to report follow-up (odds ratio = 1.65; 95% confidence interval: 1.04, 2.62), controlling for all other factors. In a national sample of women with abnormal mammograms, a substantial number did not complete any diagnostic follow-up, potentially reducing the effectiveness of mammography screening programs in the U.S. Additional research on subsequent screening behaviors for women with incomplete follow-up and in-depth exploration of the roles of patient-provider interactions and health care system factors related to the index abnormal mammogram is warranted.
Fertility Intentions Following Testing for a BRCA1 Gene Mutation
Authors: Smith Ken R. , Ellington Lee , Chan Anna Y. , Croyle Robert T. , Botkin Jeffrey R.
Published: June 2022

Objective: To test whether fertility intentions differed among persons who tested positive, tested negative, or did not know their genetic status for a mutation of the BRCA1 gene. Method: Participants were members of a large Utah-based kindred with an identified mutation at the BRCA1 locus. Participants received genetic counseling prior to testing and were interviewed at baseline before testing and at three points after receiving test results from a genetic counselor. The sample included men and women who completed all interviews, were between ages 18 and 45, and were fertile, resulting in a sample of 101 respondents. The primary dependent variable measured whether a subject indicated that they were moderately or very sure at all three post-testing interviews that they intended to have additional children. Effects of BRCA1 mutation status on fertility intentions were estimated using multivariate logistic regressions where we controlled for gender, age, marital status, and baseline fertility intentions. Results: Female carriers were less likely to want additional children in relation to female noncarriers (odds ratio 0.12, 95% confidence interval 0.01–1.23; P = 0.074). No differences were found among men. There was a significant difference in the effect of mutation status on fertility intentions between males and females (Gender × Carrier status interaction; P = 0.009). Persons who did not know their mutation status were less likely to want more children than noncarriers (odds ratio 0.09, 95% confidence interval 0.01–0.75; P = 0.027). Conclusion: Predictive genetic testing for late-onset cancer susceptibility affects family planning decision-making. Persons contemplating predictive testing should be informed about possible effects such testing may have on their plans for future fertility.
Increased Plasma Levels of Insulin-Like Growth Factor 2 and Insulin-Like Growth Factor Binding Protein 3 Are Associated with Endometrial Cancer Risk
Authors: Oh Jonathan C. , Wu Weiguo , Tortolero-Luna Guillermo , Broaddus Russell , Gershenson David M. , Burke Thomas W. , Schmandt Rosemarie , Lu Karen H.
Published: June 2022

Circulating insulin-like growth factors (IGFs) and their binding proteins have been associated with increased risk of breast, prostate, colon, and lung cancer. To examine the association of IGFs and endometrial cancer risk, we measured the plasma levels of IGF-1, IGF-2, and IGF binding protein 3 (IGFBP-3) by ELISA in 80 women with endometrial cancer and 80 age-matched control subjects with no history of cancer. Mean plasma levels of IGF-2 were significantly higher in women with cancer versus controls (670 ng/ml versus 380 ng/ml, P < 0.001). In contrast, significantly lower mean plasma levels of IGF-1 (155 mg/ml versus 185 ng/ml, P < 0.01) and IGFBP-3 (1703 ng/ml versus 2170 ng/ml, P < 0.001) were observed among cases compared to the control group. Women in the highest quartile of IGF-2 were found to have 9.67 (95% confidence interval 3.29–28.43) times the risk of endometrial cancer than women in the lowest quartiles. Women in the highest quartile of IGFBP-3 were associated with a significantly decreased risk for developing endometrial cancer (odds ratio = 0.23, 95% confidence interval 0.09–0.60). These data suggest that increased plasma levels of IGF-2 and decreased levels of IGFBP-3 are associated with an increased risk of endometrial cancer. Further validation of these results is needed to determine the potential usefulness of risk assessment.
High-Throughput Association Testing on DNA Pools to Identify Genetic Variants that Confer Susceptibility to Acute Myeloid Leukemia
Authors: Rollinson Sara , Allan James M. , Law Graham R. , Roddam Philippa L. , Smith Martyn T. , Skibola Christine , Smith Alexandra G. , Forrest Matthew S. , Sibley Kathryn , Higuchi Russell , Germer Soren , Morgan Gareth J.
Published: June 2022

We have evaluated the use of allele-specific PCR (AS PCR) on DNA pools as a tool for screening inherited genetic variants that may be associated with risk of adult acute myeloid leukemia (AML). Two DNA pools were constructed, one of 444 AML cases, and another of 823 matched controls. The pools were validated using individual genotyping data for GSTP1 and LTα variants. Allele frequencies for variants in GSTP1 and LTα were estimated using quantitative AS PCR, and when compared to individual genotyping data, a high degree of concordance was seen. AS primer pairs were designed for nine candidate genetic variants in DNA repair and cell cycle/apoptotic regulatory genes, including Cyclin D1 [codon 870 splice site variant (A>G)]; BRCA1, P871L; ERCC2, K751Q; FAS −1377 (G>A); hMLH1 −93 (G>A) and V219I; p21, S31R; and the XRCC1 R194W and R399Q variants. For six of these assays, there was at least 95% concordance between AS PCR genotyping and an alternative approach carried out on individual samples. Furthermore, these six AS PCR assays all accurately estimated allele frequencies in the pools that had been calculated using individual genotyping data. A significant disease association was seen with AML for the −1377 variant in FAS (odds ratio 1.76, 95% confidence interval 1.26–2.44). These data suggest that quantitative AS PCR can be used as an efficient screening technique for disease associations of genetic variants in DNA pools made from case-control studies.
Identifying Functional Genetic Variants in DNA Repair Pathway Using Protein Conservation Analysis
Authors: Savas Sevtap , Kim David Y. , Ahmad M. Farhan , Shariff Mehjabeen , Ozcelik Hilmi
Published: June 2022

The role of DNA repair in initiation, promotion, and progression of malignancy suggests that variations in DNA repair genes confer altered cancer risk. Accordingly, DNA repair gene variants have been studied extensively in the context of cancer predisposition. Single nucleotide polymorphisms (SNPs) are the most common genetic variations in the human genome. A fraction of SNPs are located within the genes, which are likely to alter the gene expression and function. SNPs that change the encoded amino acid sequence of the proteins (non-synonymous; nsSNPs) are potentially genetic disease determinant variations. However, as not all amino acid substitutions are supposed to lead to a change in protein function, it will be necessary to have a priori prediction and determination of the functional consequences of amino acid substitutions per se, and then together with other genetic and environmental factors to study their possible association with a trait. Here we report the analysis of nsSNPs in 88 DNA repair genes and their functional evaluation based on the conservation of amino acids among the protein family members. Our analysis demonstrated that >30% of variants of DNA repair proteins are highly likely to affect the function of the proteins drastically. In this study, we have shown that three nsSNPs, which were predicted to have functional consequences (XRCC1-R399Q, XRCC3-T241M, XRCC1-R280H), were already found to be associated with cancer risk. The strategy developed and applied in this study has the potential to identify functional protein variants of DNA repair pathway that may be associated with cancer predisposition.
Food and Botanical Groupings and Risk of Breast Cancer: A Case-Control Study in Shanghai, China
Authors: Shannon Jackilen , Ray Roberta , Wu Chenyuan , Nelson Zakia , Gao Dao Li , Li Wenjin , Hu Wei , Lampe Johanna , Horner Neilann , Satia Jessie , Patterson Ruth , Fitzgibbons Dawn , Porter Peggy , Thomas David
Published: June 2022

Breast cancer incidence rates more than double in Chinese women as they migrate from China to Hong Kong to the United States, suggesting that environmental factors contribute to the international variation in breast cancer incidence. Several dietary factors, which differ between the United States and the Chinese population, including intake of soy, meat, and fruits and vegetables, have been suggested to affect breast cancer risk. This report describes results from a case-control study of diet and risk of breast cancer nested in a randomized trial of breast self exam in Shanghai, China. Participating breast cancer cases (n = 378) and frequency age-matched controls (n = 1,070) completed a comprehensive food frequency questionnaire and a risk factor questionnaire. After adjustment for age, total energy intake, and total years of breast-feeding, women in the highest quartile of fruit and vegetable intake (≥3.8 servings/d) were significantly less likely to have breast cancer (odds ratio, 0.48; 95% confidence interval, 0.29-0.78) as compared with women in the lowest quartile of intake (≤2.3 servings/d). Egg consumption was also significantly inversely associated with risk of breast cancer (odds ratio for ≥6.0 eggs/wk versus ≤2.0 eggs/wk is 0.56; 95% confidence interval, 0.35-0.91). There was no difference in soy consumption between cases and controls. None of the associations with a single botanical family explained the strong inverse relationship between fruits and vegetables and breast cancer risk. These results provide additional evidence in support of the important role of fruits and vegetables in breast cancer prevention.