Cumulative solar ultraviolet radiation exposure and basal cell carcinoma of the skin in a nationwide US cohort using satellite and ground-based measures.

BACKGROUND: Basal cell carcinoma of the skin (BCC) is the most common cancer in populations of European ancestry. Although consistently linked with basal cell carcinoma of the skin in case-control studies, few prospective cohort studies have evaluated the shape of the exposure-response of basal cell carcinoma associated with cumulative radiant solar ultraviolet exposure (UVR). METHODS: We followed 63,912 white cancer-free US radiologic technologists from entry (1983-1998) to exit (2003-2005) with known ultraviolet irradiance at up to 5 residential locations. Using generalized-additive and relative risk models we analyzed the exposure-response of basal cell carcinomas associated with ambient cumulative ultraviolet radiant exposure using ground-based National Solar Radiation database Average Daily Total Global data and satellite-based National Aeronautics and Space Administration Total Ozone Mapping Spectrometer data. RESULTS: There were 2151 technologists with an incident primary basal cell carcinoma. Risk of basal cell carcinoma rose with increasing cumulative ultraviolet radiation exposure using both measures, such that 1 MJ cm- 2 increased basal cell carcinoma risk by 8.48 (95% CI 5.22, 11.09, p < 0.001) and by 10.15 (95% CI 6.67, 13.10, p < 0.001) per 10,000 persons per year using the Average Daily Total Global and Total Ozone Mapping Spectrometer ultraviolet data, respectively; relative risk was likewise elevated. There was some evidence of upward curvature in the cumulative ultraviolet exposure response using both exposure measures with a greater increase in risk of basal cell carcinoma at higher levels of ultraviolet radiation exposure, but less evidence for curvature in relative risk. There are indications of substantial variation of relative risk with time after exposure and age at exposure, so that risk is highest for the period 10-14 years after ultraviolet radiation exposure and for those exposed under the age of 25. CONCLUSIONS: We observed increases in risk of basal cell carcinoma and a similar exposure-response for ground-based and satellite ultraviolet radiation measures. Our observations suggest that interventions should concentrate on persons with higher levels of ultraviolet radiation exposure.

Occupational radiation exposure and thyroid cancer incidence in a cohort of U.S. radiologic technologists, 1983-2013.

Although childhood exposure to ionizing radiation is a well-established risk factor for thyroid cancer, the risk associated with adulthood exposure remains unclear. We prospectively examined the association between cumulative, low-to-moderate dose occupational radiation exposure to the thyroid and thyroid cancer incidence in the U.S. Radiologic Technologists cohort. The study included 89,897 members who completed at least two of four mailed questionnaires and were cancer-free at the time of the first questionnaire. Cumulative occupational thyroid radiation dose (mean = 57 mGy, range = 0-1,600 mGy) was estimated based on self-reported work histories, historical data and, during the years 1960-1997, 783,000 individual film badge measurements. During follow-up, we identified 476 thyroid cancer cases. We used Poisson regression to estimate excess relative risk of thyroid cancer per 100 milliGray (ERR/100 mGy) absorbed dose to the thyroid gland. After adjusting for attained age, sex, birth year, body mass index and pack-years smoked, we found no association between thyroid dose and thyroid cancer risk (ERR/100 mGy = -0.05, 95% CI <-0.10, 0.34). In this large cohort study of radiologic technologists, protracted, low-to-moderate dose ionizing radiation exposure to the thyroid gland in adulthood was not associated with an increased risk of thyroid cancer.

Melanoma, thyroid cancer, and gynecologic cancers in a cohort of female flight attendants.

BACKGROUND: Flight attendants may have an increased risk of some cancers from occupational exposure to cosmic radiation and circadian disruption. METHODS: The incidence of thyroid, ovarian, and uterine cancer among ∼6000 female flight attendants compared to the US population was evaluated via life table analyses. Associations of these cancers, melanoma, and cervical cancer with cumulative cosmic radiation dose and metrics of circadian disruption were evaluated using Cox regression. RESULTS: Incidence of thyroid, ovarian, and uterine cancer was not elevated. No significant, positive exposure-response relations were observed. Weak, non-significant, positive relations were observed for thyroid cancer with cosmic radiation and time zones crossed and for melanoma with another metric of circadian disruption. CONCLUSIONS: We found little evidence of increased risk of these cancers from occupational cosmic radiation or circadian disruption in female flight attendants. Limitations include few observed cases of some cancers, limited data on risk factors, and misclassification of exposures.

Selected single-nucleotide polymorphisms in FOXE1, SERPINA5, FTO, EVPL, TICAM1 and SCARB1 are associated with papillary and follicular thyroid cancer risk: replication study in a German population.

Several single-nucleotide polymorphisms (SNPs) have been associated with papillary and follicular thyroid cancer (PTC and FTC, respectively) risk, but few have replicated. After analyzing 17525 tag SNPs in 1129 candidate genes, we found associations with PTC risk in SERPINA5, FTO, HEMGN (near FOXE1) and other genes. Here, we report results from a replication effort in a large independent PTC/FTC case-control study conducted in Germany. We evaluated the best tagging SNPs from our previous PTC study and additionally included SNPs in or near FOXE1 and NKX2-1 genes, known susceptibility loci for thyroid cancer. We genotyped 422 PTC and 130 FTC cases and 752 controls recruited from three German clinical centers. We used polytomous logistic regression to simultaneously estimate PTC and FTC associations for 79 SNPs based on log-additive models. We assessed effect modification by body mass index (BMI), gender and age for all SNPs, and selected SNP by SNP interactions. We confirmed associations with PTC and SNPs in FOXE1/HEMGN, SERPINA5 (rs2069974), FTO (rs8047395), EVPL (rs2071194), TICAM1 (rs8120) and SCARB1 (rs11057820) genes. We found associations with SNPs in FOXE1, SERPINA5, FTO, TICAM1 and HSPA6 and FTC. We found two significant interactions between FTO (rs8047395) and BMI (P = 0.0321) and between TICAM1 (rs8120) and FOXE1 (rs10984377) (P = 0.0006). Besides the known associations with FOXE1 SNPs, we confirmed additional PTC SNP associations reported previously. We also found several new associations with FTC risk and noteworthy interactions. We conclude that multiple variants and host factors might interact in complex ways to increase risk of PTC and FTC.

Changing Patterns in the Performance of Fluoroscopically Guided Interventional Procedures and Adherence to Radiation Safety Practices in a U.S. Cohort of Radiologic Technologists.

OBJECTIVE: Information is limited on changes over time in the types of fluoroscopically guided interventional procedures performed and associated radiation safety practices used by radiologic technologists. MATERIALS AND METHODS: Our study included 12,571 U.S. radiologic technologists who were certified for at least 2 years in 1926-1982 and who reported in a 2012-2013 survey that they ever performed or assisted with fluoroscopically guided interventional procedures. They completed a mailed questionnaire in 2013-2014 describing their detailed work practices for 21 fluoroscopically guided interventional procedures and associated radiation safety practices from the 1950s through 2009. RESULTS: Overall, the proportion of technologists who reported working with therapeutic fluoroscopically guided interventional procedures, including percutaneous coronary interventions, increased over time, whereas the proportion of technologists who worked with diagnostic fluoroscopically guided interventional procedures, including diagnostic cardiovascular catheterization and neuroangiographic procedures, decreased. We also observed substantial increases in the median number of times per month that technologists worked with diagnostic cardiovascular catheterizations and percutaneous coronary interventions. In each time period, most technologists reported consistently (≥ 75% of work time) wearing radiation monitoring badges and lead aprons during fluoroscopically guided interventional procedures. However, fewer than 50% of the technologists reported consistent use of thyroid shields, lead glasses, and room shields during fluoroscopically guided interventional procedures, even in more recent time periods. CONCLUSION: This study provides a detailed historical assessment of fluoroscopically guided interventional procedures performed and radiation safety practices used by radiologic technologists from the 1950s through 2009. Results can be used in conjunction with badge dose data to estimate organ radiation dose for studies of radiation-related health risks in radiologic technologists who have worked with fluoroscopically guided interventional procedures.

Cancer Risks in U.S. Radiologic Technologists Working With Fluoroscopically Guided Interventional Procedures, 1994-2008.

OBJECTIVE: The purpose of this study was to examine risks of cancer incidence and mortality among U.S. radiation technologists performing or assisting with fluoroscopically guided interventional procedures. SUBJECTS AND METHODS: A nationwide prospective cohort of 90,957 radiologic technologists, who responded to a 1994-1998 survey that collected information on whether they had ever worked with fluoroscopically guided interventional procedures, was followed through completion of a subsequent cohort survey during 2003-2005 (for cancer incidence) or December 31, 2008 (for cancer mortality). Sex-adjusted hazard ratios (HRs) and 95% CIs were calculated by use of Cox proportional hazards models for incidence and mortality from all cancers other than nonmelanoma skin cancer and for specific cancer outcomes in participants who reported ever performing fluoroscopically guided interventional procedures compared with technologists who never performed these procedures. RESULTS: The analysis showed an approximately twofold increased risk of brain cancer mortality (HR, 2.55; 95% CI, 1.48-4.40) and modest elevations in incidence of melanoma (HR, 1.30; 95% CI, 1.05-1.61) and in breast cancer incidence (HR, 1.16; 95% CI, 1.02-1.32) but not mortality (HR, 1.07; 95% CI, 0.69-1.66) among technologists who performed fluoroscopically guided interventional procedures compared with those who never performed these procedures. Although there was a small suggestive increase in incidence of all cancers combined, excluding nonmelanoma skin cancers (HR, 1.08; 95% CI, 1.00-1.17), mortality from all cancers combined, excluding nonmelanoma skin cancers, was not elevated (HR, 1.00; 95% CI, 0.88-1.14). We similarly observed no elevated risk of cancers of the thyroid, skin other than melanoma, prostate, lung, or colon and rectum or of leukemia that was not chronic lymphocytic leukemia among workers who performed fluoroscopically guided interventional procedures. CONCLUSION: We observed elevated risks of brain cancer, breast cancer, and melanoma among technologists who performed fluoroscopically guided interventional procedures. Although exposure to low-dose radiation is one possible explanation for these increased risks, these results may also be due to chance or unmeasured confounding by nonradiation risk factors. Our results must be confirmed in other studies, preferably with individual radiation dose data.

Incidence and mortality risks for circulatory diseases in US radiologic technologists who worked with fluoroscopically guided interventional procedures, 1994-2008.

OBJECTIVES: Although fluoroscopically guided interventional procedures (FGIP) have provided major advances in the treatment of various common diseases, radiation exposures associated with these procedures may cause adverse health effects in workers. We assess risk of circulatory disease incidence and mortality in medical radiation workers performing FGIP. METHODS: A US nationwide prospective cohort study of 90,957 radiologic technologists who completed a cohort survey during 1994-1998 was followed until completion of a subsequent survey during 2003-2005 for circulatory disease incidence, or until 31 December 2008 for mortality. Incidence analyses were restricted to the 63,482 technologists who completed both the second survey (1994-1998) and the third survey (2003-2005). Cox proportional hazards models were used to assess adjusted HR and 95% CIs for mortality from all causes, all circulatory diseases, all heart diseases, ischaemic heart disease, stroke, acute myocardial infarction and hypertension in participants who reported ever performing FGIP compared to technologists who never performed FGIP procedures. Adjusted HRs were calculated for self-reported hypertension, stroke and myocardial infarction. RESULTS: We observed a 34% increase in stroke incidence (HR=1.34, 95% CI 1.10 to 1.64) in technologists who performed FGIP compared to those who never performed these procedures. Mortality from stroke was also modestly elevated, although not statistically significant (HR=1.22, 95% CI 0.85 to 1.73). We observed no statistically significant excess risks of incidence or mortality from any other outcome evaluated. CONCLUSIONS: Our finding of elevated risk of stroke in workers performing FGIP needs to be confirmed in studies with individual radiation dose data, but nonetheless underlines the need to keep radiation exposure as low as reasonably achievable without compromising key diagnostic information.

Occupational ionising radiation and risk of basal cell carcinoma in US radiologic technologists (1983-2005).

OBJECTIVE: To determine risk for incident basal cell carcinoma from cumulative low-dose ionising radiation in the US radiologic technologist cohort. METHODS: We analysed 65,719 Caucasian technologists who were cancer-free at baseline (1983-1989 or 1994-1998) and answered a follow-up questionnaire (2003-2005). Absorbed radiation dose to the skin in mGy for estimated cumulative occupational radiation exposure was reconstructed for each technologist based on badge dose measurements, questionnaire-derived work history and protection practices, and literature information. Radiation-associated risk was assessed using Poisson regression and included adjustment for several demographic, lifestyle, host and sun exposure factors. RESULTS: Cumulative mean absorbed skin dose (to head/neck/arms) was 55.8 mGy (range 0-1735 mGy). For lifetime cumulative dose, we did not observe an excess radiation-related risk (excess relative risk/Gy=-0.01 (95% CI -0.43 to 0.52). However, we observed that basal cell carcinoma risk was increased for radiation dose received before age 30 (excess relative risk/Gy=0.59, 95% CI -0.11 to 1.42) and before 1960 (excess relative risk/Gy=2.92, 95% CI 1.39 to 4.45). CONCLUSIONS: Basal cell carcinoma risk was unrelated to low-dose radiation exposure among radiologic technologists. Because of uncertainties in dosimetry and sensitivity to model specifications, both our null results and our findings of excess risk for dose received before age 30 and exposure before 1960 should be interpreted with caution.

Breast cancer incidence in a cohort of U.S. flight attendants.

BACKGROUND: Flight attendants may have elevated breast cancer incidence (BCI). We evaluated BCI's association with cosmic radiation dose and circadian rhythm disruption among 6,093 female former U.S. flight attendants. METHODS: We collected questionnaire data on BCI and risk factors for breast cancer from 2002-2005. We conducted analyses to evaluate (i) BCI in the cohort compared to the U.S. population; and (ii) exposure-response relations. We applied an indirect adjustment to estimate whether parity and age at first birth (AFB) differences between the cohort and U.S. population could explain BCI that differed from expectation. RESULTS: BCI was elevated but may be explained by lower parity and older AFB in the cohort than among U.S. women. BCI was not associated with exposure metrics in the cohort overall. Significant positive associations with both were observed only among women with parity of three or more. CONCLUSIONS: Future cohort analyses may be informative on the role of these occupational exposures and non-occupational risk factors.

A prospective study of medical diagnostic radiography and risk of thyroid cancer.

Although diagnostic x-ray procedures provide important medical benefits, cancer risks associated with their exposure are also possible, but not well characterized. The US Radiologic Technologists Study (1983-2006) is a nationwide, prospective cohort study with extensive questionnaire data on history of personal diagnostic imaging procedures collected prior to cancer diagnosis. We used Cox proportional hazard regressions to estimate thyroid cancer risks related to the number and type of selected procedures. We assessed potential modifying effects of age and calendar year of the first x-ray procedure in each category of procedures. Incident thyroid cancers (n = 251) were diagnosed among 75,494 technologists (1.3 million person-years; mean follow-up = 17 years). Overall, there was no clear evidence of thyroid cancer risk associated with diagnostic x-rays except for dental x-rays. We observed a 13% increase in thyroid cancer risk for every 10 reported dental radiographs (hazard ratio = 1.13, 95% confidence interval: 1.01, 1.26), which was driven by dental x-rays first received before 1970, but we found no evidence that the relationship between dental x-rays and thyroid cancer was associated with childhood or adolescent exposures as would have been anticipated. The lack of association of thyroid cancer with x-ray procedures that expose the thyroid to higher radiation doses than do dental x-rays underscores the need to conduct a detailed radiation exposure assessment to enable quantitative evaluation of risk.

A role for XRCC2 gene polymorphisms in breast cancer risk and survival.

BACKGROUND: The XRCC2 gene is a key mediator in the homologous recombination repair of DNA double strand breaks. It is hypothesised that inherited variants in the XRCC2 gene might also affect susceptibility to, and survival from, breast cancer. METHODS: The study genotyped 12 XRCC2 tagging single nucleotide polymorphisms (SNPs) in 1131 breast cancer cases and 1148 controls from the Sheffield Breast Cancer Study (SBCS), and examined their associations with breast cancer risk and survival by estimating ORs and HRs, and their corresponding 95% CIs. Positive findings were further investigated in 860 cases and 869 controls from the Utah Breast Cancer Study (UBCS) and jointly analysed together with available published data for breast cancer risk. The survival findings were further confirmed in studies (8074 cases) from the Breast Cancer Association Consortium (BCAC). RESULTS: The most significant association with breast cancer risk in the SBCS dataset was the XRCC2 rs3218408 SNP (recessive model p=2.3×10(-4), minor allele frequency (MAF)=0.23). This SNP yielded an OR(rec) of 1.64 (95% CI 1.25 to 2.16) in a two-site analysis of SBCS and UBCS, and a meta-OR(rec) of 1.33 (95% CI 1.12 to 1.57) when all published data were included. This SNP may mark a rare risk haplotype carried by two in 1000 of the control population. Furthermore, the XRCC2 coding R188H SNP (rs3218536, MAF=0.08) was significantly associated with poor survival, with an increased per-allele HR of 1.58 (95% CI 1.01 to 2.49) in a multivariate analysis. This effect was still evident in a pooled meta-analysis of 8781 breast cancer patients from the BCAC (HR 1.19, 95% CI 1.05 to 1.36; p=0.01). CONCLUSIONS: These findings suggest that XRCC2 SNPs may influence breast cancer risk and survival.

Prospective analysis of DNA damage and repair markers of lung cancer risk from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.

Mutagen challenge and DNA repair assays have been used in case-control studies for nearly three decades to assess human cancer risk. The findings still engender controversy because blood was drawn after cancer diagnosis so the results may be biased, a type called 'reverse causation'. We therefore used Epstein-Barr virus-transformed lymphoblastoid cell lines established from prospectively collected peripheral blood samples to evaluate lung cancer risk in relation to three DNA repair assays: alkaline Comet assay, host cell reactivation (HCR) assay with the mutagen benzo[a]pyrene diol epoxide and the bleomycin mutagen sensitivity assay. Cases (n = 117) were diagnosed with lung cancer between 0.3 and 6 years after blood collection and controls (n = 117) were frequency matched on calendar year and age at blood collection, gender and smoking history; all races were included. Case and control status was unknown to laboratory investigators. In unconditional logistic regression analyses, statistically significantly increased lung cancer odds ratios (OR(adjusted)) were observed for bleomycin mutagen sensitivity as quartiles of chromatid breaks/cell [relative to the lowest quartile, OR = 1.2, 95% confidence interval (CI): 0.5-2.5; OR = 1.4, 95% CI: 0.7-3.1; OR = 2.1, 95% CI: 1.0-4.4, respectively, P(trend) = 0.04]. The magnitude of the association between the bleomycin assay and lung cancer risk was modest compared with those reported in previous lung cancer studies but was strengthened when we included only incident cases diagnosed more than a year after blood collection (P(trend) = 0.02), supporting the notion the assay may be a measure of cancer susceptibility. The Comet and HCR assays were unrelated to lung cancer risk.

Common genetic variants related to genomic integrity and risk of papillary thyroid cancer.

DNA damage is an important mechanism in carcinogenesis, so genes related to maintaining genomic integrity may influence papillary thyroid cancer (PTC) risk. Candidate gene studies targeting some of these genes have identified only a few polymorphisms associated with risk of PTC. Here, we expanded the scope of previous candidate studies by increasing the number and coverage of genes related to maintenance of genomic integrity. We evaluated 5077 tag single-nucleotide polymorphisms (SNPs) from 340 candidate gene regions hypothesized to be involved in DNA repair, epigenetics, tumor suppression, apoptosis, telomere function and cell cycle control and signaling pathways in a case-control study of 344 PTC cases and 452 matched controls. We estimated odds ratios for associations of single SNPs with PTC risk and combined P values for SNPs in the same gene region or pathway to obtain gene region-specific or pathway-specific P values using adaptive rank-truncated product methods. Nine SNPs had P values <0.0005, three of which were in HDAC4 and were inversely related to PTC risk. After multiple comparisons adjustment, no SNPs remained associated with PTC risk. Seven gene regions were associated with PTC risk at P < 0.01, including HUS1, ALKBH3, HDAC4, BAK1, FAF1_CDKN2C, DACT3 and FZD6. Our results suggest a possible role of genes involved in maintenance of genomic integrity in relation to risk of PTC.

Nonsteroidal antiinflammatory drugs and bladder cancer: a pooled analysis.

Case-control studies have shown that regular use of nonsteroidal antiinflammatory drugs (NSAIDs) decreases bladder cancer risk, but few cohort studies have evaluated this association. The authors investigated NSAID use and bladder cancer in 3 large prospective studies (NIH-AARP Diet and Health Study; Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial; and U.S. Radiologic Technologists Study). Frequency of aspirin and nonaspirin NSAID use 1 year prior to baseline was ascertained using self-administered questionnaires. Study-specific hazard ratios and 95% confidence intervals were estimated using Cox regression models and were combined using a fixed-effects meta-analytic model. Data from all studies were aggregated, and aggregated hazard ratios were estimated. The analysis included 508,842 individuals, with 2,489 incident cases of bladder cancer. A reduction in risk was observed for individuals who reported regular use (>2 times/week) of nonaspirin NSAIDs compared with those who reported no use (hazard ratio (HR) = 0.92, 95% confidence interval (CI): 0.81, 1.04). The risk reduction was limited to nonsmokers (HR = 0.58, 95% CI: 0.41, 0.83) (P(trend) = 0.008) (P(interaction) = 0.02). No association was observed between regular aspirin use and bladder cancer risk (HR = 1.04, 95% CI: 0.94, 1.15). Results suggest that nonaspirin NSAIDs, but not aspirin, are associated with a reduction in risk of bladder cancer, particularly for nonsmokers.

Hormone-related risk factors and postmenopausal breast cancer among nulliparous versus parous women: An aggregated study.

Nulliparity is an established breast cancer risk factor, particularly when compared with parity at young ages. The authors aggregated data from 4 US prospective studies (1979-2006) including 32,641 nulliparous (1,612 breast cancers) and 204,270 parous (8,180 breast cancers) women to examine the hypothesis that nulliparity may increase susceptibility to established postmenopausal breast cancer risk factors. The aggregated hazard ratio for nulliparous versus all parous women = 1.27 (95% confidence interval: 1.21, 1.34), and that for nulliparous versus women <25 years of age at first birth = 1.38 (95% confidence interval: 1.30, 1.46). Among nulliparous women, the hazard ratios for current menopausal hormone therapy use (vs. never use), body mass index ≥30 kg/m(2) (vs. <25 kg/m(2)), and weekly consumption of ≥7 alcoholic drinks (vs. none) ranged from 1.3 to 1.6. The hazard ratios did not differ by parity. In a model including all women, the joint association for each of these factors and nulliparity combined compared with first birth before age 25 years was an approximately 2-fold increased breast cancer risk. Although the baseline risk is higher for nulliparous women compared with parous women, these results suggest that the associations between hormone-related factors and breast cancer do not differ by parity.

Variation in base excision repair capacity.

The major DNA repair pathway for coping with spontaneous forms of DNA damage, such as natural hydrolytic products or oxidative lesions, is base excision repair (BER). In particular, BER processes mutagenic and cytotoxic DNA lesions such as non-bulky base modifications, abasic sites, and a range of chemically distinct single-strand breaks. Defects in BER have been linked to cancer predisposition, neurodegenerative disorders, and immunodeficiency. Recent data indicate a large degree of sequence variability in DNA repair genes and several studies have associated BER gene polymorphisms with disease risk, including cancer of several sites. The intent of this review is to describe the range of BER capacity among individuals and the functional consequences of BER genetic variants. We also discuss studies that associate BER deficiency with disease risk and the current state of BER capacity measurement assays.

Assessing interactions between the associations of common genetic susceptibility variants, reproductive history and body mass index with breast cancer risk in the breast cancer association consortium: a combined case-control study.

INTRODUCTION: Several common breast cancer genetic susceptibility variants have recently been identified. We aimed to determine how these variants combine with a subset of other known risk factors to influence breast cancer risk in white women of European ancestry using case-control studies participating in the Breast Cancer Association Consortium. METHODS: We evaluated two-way interactions between each of age at menarche, ever having had a live birth, number of live births, age at first birth and body mass index (BMI) and each of 12 single nucleotide polymorphisms (SNPs) (10q26-rs2981582 (FGFR2), 8q24-rs13281615, 11p15-rs3817198 (LSP1), 5q11-rs889312 (MAP3K1), 16q12-rs3803662 (TOX3), 2q35-rs13387042, 5p12-rs10941679 (MRPS30), 17q23-rs6504950 (COX11), 3p24-rs4973768 (SLC4A7), CASP8-rs17468277, TGFB1-rs1982073 and ESR1-rs3020314). Interactions were tested for by fitting logistic regression models including per-allele and linear trend main effects for SNPs and risk factors, respectively, and single-parameter interaction terms for linear departure from independent multiplicative effects. RESULTS: These analyses were applied to data for up to 26,349 invasive breast cancer cases and up to 32,208 controls from 21 case-control studies. No statistical evidence of interaction was observed beyond that expected by chance. Analyses were repeated using data from 11 population-based studies, and results were very similar. CONCLUSIONS: The relative risks for breast cancer associated with the common susceptibility variants identified to date do not appear to vary across women with different reproductive histories or body mass index (BMI). The assumption of multiplicative combined effects for these established genetic and other risk factors in risk prediction models appears justified.

The impact of delayed blood centrifuging, choice of collection tube, and type of assay on 25-hydroxyvitamin D concentrations.

Studies have examined the associations between cancers and circulating 25-hydroxyvitamin D [25(OH)D], but little is known about the impact of different laboratory practices on 25(OH)D concentrations. We examined the potential impact of delayed blood centrifuging, choice of collection tube, and type of assay on 25(OH)D concentrations. Blood samples from 20 healthy volunteers underwent alternative laboratory procedures: four centrifuging times (2, 24, 72, and 96 h after blood draw); three types of collection tubes (red top serum tube, two different plasma anticoagulant tubes containing heparin or EDTA); and two types of assays (DiaSorin radioimmunoassay [RIA] and chemiluminescence immunoassay [CLIA/LIAISON((R))]). Log-transformed 25(OH)D concentrations were analyzed using the generalized estimating equations (GEE) linear regression models. We found no difference in 25(OH)D concentrations by centrifuging times or type of assay. There was some indication of a difference in 25(OH)D concentrations by tube type in CLIA/LIAISON((R))-assayed samples, with concentrations in heparinized plasma (geometric mean, 16.1 ng ml(-1)) higher than those in serum (geometric mean, 15.3 ng ml(-1)) (p = 0.01), but the difference was significant only after substantial centrifuging delays (96 h). Our study suggests no necessity for requiring immediate processing of blood samples after collection or for the choice of a tube type or assay.

Polymorphisms in oxidative stress and inflammation pathway genes, low-dose ionizing radiation, and the risk of breast cancer among US radiologic technologists.

OBJECTIVE: Ionizing radiation, an established breast cancer risk factor, has been shown to induce oxidative damage and chronic inflammation. Polymorphic variation in oxidative stress and inflammatory-mediated pathway genes may modify radiation-related breast cancer risk. METHODS: We estimated breast cancer risk for 28 common variants in 16 candidate genes involved in these pathways among 859 breast cancer cases and 1,083 controls nested within the US Radiologic Technologists cohort. We estimated associations between occupational and personal diagnostic radiation exposures with breast cancer by modeling the odds ratio (OR) as a linear function in logistic regression models and assessed heterogeneity of the dose-response across genotypes. RESULTS: There was suggestive evidence of an interaction between the rs5277 variant in PTGS2 and radiation-related breast cancer risk. The excess OR (EOR)/Gy from occupational radiation exposure = 5.5 (95%CI 1.2-12.5) for the GG genotype versus EOR/Gy < 0 (95%CI < 0-3.8) and EOR/Gy < 0 (95%CI < 0-14.8) for the GC and CC genotypes, respectively, (p (interaction) = 0.04). The association between radiation and breast cancer was not modified by other SNPs examined. CONCLUSIONS: This study suggests that variation in PTGS2 may modify the breast cancer risk from occupational radiation exposure, but replication in other populations is needed to confirm this result.

Diagnostic X-ray examinations and increased chromosome translocations: evidence from three studies.

Controversy regarding potential health risks from increased use of medical diagnostic radiologic examinations has come to public attention. We evaluated whether chromosome damage, specifically translocations, which are a potentially intermediate biomarker for cancer risk, was increased after exposure to diagnostic X-rays, with particular interest in the ionizing radiation dose-response below the level of approximately 50 mGy. Chromosome translocation frequency data from three separately conducted occupational studies of ionizing radiation were pooled together. Studies 1 and 2 included 79 and 150 medical radiologic technologists, respectively, and study 3 included 83 airline pilots and 50 university faculty members (total = 155 women and 207 men; mean age = 62 years, range 34-90). Information on personal history of radiographic examinations was collected from a detailed questionnaire. We computed a cumulative red bone marrow (RBM) dose score based on the numbers and types of X-ray examinations reported with 1 unit approximating 1 mGy. Poisson regression analyses were adjusted for age and laboratory method. Mean RBM dose scores were 49, 42, and 11 for Studies 1-3, respectively (overall mean = 33.5, range 0-303). Translocation frequencies significantly increased with increasing dose score (P < 0.001). Restricting the analysis to the lowest dose scores of under 50 did not materially change these results. We conclude that chromosome damage is associated with low levels of radiation exposure from diagnostic X-ray examinations, including dose scores of approximately 50 and lower, suggesting the possibility of long-term adverse health effects.