Breast cancer risk and protracted low-to-moderate dose occupational radiation exposure in the US Radiologic Technologists Cohort, 1983-2008.

BACKGROUND: Although high-dose ionising radiation is associated with increased breast cancer risks, the association with protracted low-dose-rate exposures remains unclear. The US Radiologic Technologist study provides an opportunity to examine the association between low-to-moderate dose radiation and breast cancer incidence and mortality. METHODS: One thousand nine hundred and twenty-two self-reported first primary cancers were diagnosed during 1983-2005 among 66 915 female technologists, and 586 breast cancer deaths occurred during 1983-2008 among 83 538 female cohort members. Occupational breast dose estimates were based on work histories, historical data, and, after the mid-1970s, individual film badge measurements. Excess relative risks were estimated using Poisson regression with birth cohort stratification and adjustment for menopause, reproductive history, and other risk factors. RESULTS: Higher doses were associated with increased breast cancer incidence, with an excess relative risk at 100 mGy of 0.07 (95% confidence interval (CI): -0.005 to 0.19). Associations were strongest for technologists born before 1930 (excess relative risk at 100 mGy=0.16; 95% CI: 0.03-0.39) with similar patterns for mortality among technologists born before 1930. CONCLUSIONS: Occupational radiation to the breast was positively associated with breast cancer risk. The risk was more pronounced for women born before 1930 who began working before 1950 when mean annual doses (37 mGy) were considerably higher than in later years (1.3 mGy). However, because of the uncertainties and possible systematic errors in the occupational dose estimates before 1960, these findings should be treated with caution.

Reproductive factors, exogenous hormone use and risk of hepatocellular carcinoma among US women: results from the Liver Cancer Pooling Project.

BACKGROUND: Hepatocellular carcinoma (HCC) occurs less commonly among women than men in almost all regions of the world. The disparity in risk is particularly notable prior to menopause suggesting that hormonal exposures during reproductive life may be protective. Exogenous oestrogenic exposures such as oral contraceptives (OCs), however, have been reported to increase risk, suggesting that estrogens may be hepatocarcinogenic. To examine the effects of reproductive factors and exogenous hormones on risk, we conducted a prospective analysis among a large group of US women. METHODS: In the Liver Cancer Pooling Project, a consortium of US-based cohort studies, data from 799,500 women in 11 cohorts were pooled and harmonised. Cox proportional hazards regression models were used to generate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of reproductive factors and exogenous hormones with HCC (n=248). RESULTS: Bilateral oophorectomy was associated with a significantly increased risk of HCC (HR=2.67, 95% CI=1.22-5.85), which did not appear to be related to a shorter duration of exposure to endogenous hormones or to menopausal hormone therapy use. There was no association between OC use and HCC (HR=1.12, 95% CI=0.82-1.55). Nor were there associations with parity, age at first birth, age at natural menopause, or duration of fertility. CONCLUSIONS: The current study suggests that bilateral oophorectomy increases the risk of HCC but the explanation for the association is unclear. There was no association between OC use and HCC risk. Examination of endogenous hormone levels in relation to HCC may help to clarify the findings of the current study.

Common genetic variants in the 9p21 region and their associations with multiple tumours.

BACKGROUND: The chromosome 9p21.3 region has been implicated in the pathogenesis of multiple cancers. METHODS: We systematically examined up to 203 tagging SNPs of 22 genes on 9p21.3 (19.9-32.8 Mb) in eight case-control studies: thyroid cancer, endometrial cancer (EC), renal cell carcinoma, colorectal cancer (CRC), colorectal adenoma (CA), oesophageal squamous cell carcinoma (ESCC), gastric cardia adenocarcinoma and osteosarcoma (OS). We used logistic regression to perform single SNP analyses for each study separately, adjusting for study-specific covariates. We combined SNP results across studies by fixed-effect meta-analyses and a newly developed subset-based statistical approach (ASSET). Gene-based P-values were obtained by the minP method using the Adaptive Rank Truncated Product program. We adjusted for multiple comparisons by Bonferroni correction. RESULTS: Rs3731239 in cyclin-dependent kinase inhibitors 2A (CDKN2A) was significantly associated with ESCC (P=7 × 10(-6)). The CDKN2A-ESCC association was further supported by gene-based analyses (Pgene=0.0001). In the meta-analyses by ASSET, four SNPs (rs3731239 in CDKN2A, rs615552 and rs573687 in CDKN2B and rs564398 in CDKN2BAS) showed significant associations with ESCC and EC (P<2.46 × 10(-4)). One SNP in MTAP (methylthioadenosine phosphorylase) (rs7023329) that was previously associated with melanoma and nevi in multiple genome-wide association studies was associated with CRC, CA and OS by ASSET (P=0.007). CONCLUSION: Our data indicate that genetic variants in CDKN2A, and possibly nearby genes, may be associated with ESCC and several other tumours, further highlighting the importance of 9p21.3 genetic variants in carcinogenesis.

Baldness, acne and testicular germ cell tumours.

Androgen levels during critical periods of testicular development may be involved in the aetiology of testicular germ cell tumours (TGCT). We evaluated the roles of adolescent and early adult life correlates of androgen exposure and TGCT in a hospital-based case-control study. TGCT cases (n=187) and controls (n=148), matched on age, race and state of residence, participated in the study. Unconditional logistic regression was used to estimate associations between TGCT and male pattern baldness, severe acne, markers of puberty onset and body size. Cases were significantly less likely to report hair loss than controls [odds ratio (OR): 0.6; 95% confidence interval (CI): 0.4, 1.0]. Amount of hair loss, increasing age at onset and increasing rate of loss were all inversely associated with TGCT (rate of hair loss: p-trend=0.03; age at onset: p-trend=0.03; amount of hair loss: p-trend=0.01). History of severe acne was inversely associated with TGCT (OR: 0.5; 95% CI: 0.3, 0.9) and height was positively associated with TGCT (p-trend=0.02). Increased endogenous androgen levels during puberty and early adulthood may be associated with a decreased risk of TGCT. Additional studies of endogenous hormone levels during puberty and early adult life are warranted, especially studies evaluating the role of androgen synthesis, metabolism and uptake.

Endogenous DNA damage and testicular germ cell tumors.

Testicular germ cell tumors are comprised of two histologic groups, seminomas and non-seminomas. We postulated that the possible divergent pathogeneses of these histologies may be partially explained by variable levels of net endogenous DNA damage. To test our hypothesis, we conducted a case-case analysis of 51 seminoma and 61 non-seminoma patients using data and specimens from the Familial Testicular Cancer study and the U.S. Radiologic Technologists cohort. A lymphoblastoid cell line was cultured for each patient and the alkaline comet assay was used to determine four parameters: tail DNA, tail length, comet distributed moment (CDM) and Olive tail moment (OTM). Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using logistic regression. Values for tail length, tail DNA, CDM and OTM were modelled as categorical variables using the 50th and 75th percentiles of the seminoma group. Tail DNA was significantly associated with non-seminoma compared with seminoma (OR(50th percentile) = 3.31, 95% CI: 1.00, 10.98; OR(75th percentile) = 3.71, 95% CI: 1.04, 13.20; p for trend = 0.039). OTM exhibited similar, albeit statistically non-significant, risk estimates (OR(50th percentile) = 2.27, 95% CI: 0.75, 6.87; OR(75th percentile) = 2.40, 95% CI: 0.75, 7.71; p for trend = 0.12) whereas tail length and CDM showed no association. In conclusion, the results for tail DNA and OTM indicate that net endogenous levels are higher in patients who develop non-seminoma compared with seminoma. This may partly explain the more aggressive biology and younger age-of-onset of this histologic subgroup compared with the relatively less aggressive, later-onset seminoma.

Increased frequency of chromosome translocations in airline pilots with long-term flying experience.

BACKGROUND: Chromosome translocations are an established biomarker of cumulative exposure to external ionising radiation. Airline pilots are exposed to cosmic ionising radiation, but few flight crew studies have examined translocations in relation to flight experience. METHODS: We determined the frequency of translocations in the peripheral blood lymphocytes of 83 airline pilots and 50 comparison subjects (mean age 47 and 46 years, respectively). Translocations were scored in an average of 1039 cell equivalents (CE) per subject using fluorescence in situ hybridisation (FISH) whole chromosome painting and expressed per 100 CE. Negative binomial regression models were used to assess the relationship between translocation frequency and exposure status and flight years, adjusting for age, diagnostic x ray procedures, and military flying. RESULTS: There was no significant difference in the adjusted mean translocation frequency of pilots and comparison subjects (0.37 (SE 0.04) vs 0.38 (SE 0.06) translocations/100 CE, respectively). However, among pilots, the adjusted translocation frequency was significantly associated with flight years (p = 0.01) with rate ratios of 1.06 (95% CI 1.01 to 1.11) and 1.81 (95% CI 1.16 to 2.82) for a 1- and 10-year incremental increase in flight years, respectively. The adjusted rate ratio for pilots in the highest compared to the lowest quartile of flight years was 2.59 (95% CI 1.26 to 5.33). CONCLUSIONS: Our data suggests that pilots with long-term flying experience may be exposed to biologically significant doses of ionising radiation. Epidemiological studies with longer follow-up of larger cohorts of pilots with a wide range of radiation exposure levels are needed to clarify the relationship between cosmic radiation exposure and cancer risk.

Childhood cancer in the offspring born in 1921-1984 to US radiologic technologists.

We examined the risk of childhood cancer (<20 years) among 105 950 offspring born in 1921-1984 to US radiologic technologist (USRT) cohort members. Parental occupational in utero and preconception ionising radiation (IR) testis or ovary doses were estimated from work history data, badge dose data, and literature doses (the latter doses before 1960). Female and male RTs reported a total of 111 and 34 haematopoietic malignancies and 115 and 34 solid tumours, respectively, in their offspring. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression. Leukaemia (n=63) and solid tumours (n=115) in offspring were not associated with maternal in utero or preconception radiation exposure. Risks for lymphoma (n=44) in those with estimated doses of <0.2, 0.2-1.0, and >1.0 mGy vs no exposure were non-significantly elevated with HRs of 2.3, 1.8, and 2.7. Paternal preconception exposure to estimated cumulative doses above the 95th percentile (82 mGy, n=6 cases) was associated with a non-significant risk of childhood cancer of 1.8 (95% CI 0.7-4.6). In conclusion, we found no convincing evidence of an increased risk of childhood cancer in the offspring of RTs in association with parental occupational radiation exposure.

Gamma-ray mutagen sensitivity and survival in patients with glioma.

Despite advances in treatment of brain tumors, cerebral malignant gliomas are rapidly debilitating with poor survival. Patient age and tumor histology are known to influence survival in glioma patients, but these factors do not account for all of the variability in survival time. To identify additional useful predictors, we tested an assay that measures intrinsic gamma-ray mutagen sensitivity. Our hypothesis was that increased sensitivity of peripheral blood lymphocytes to chromatid breaks is associated with tumor aggressiveness and decreased patient survival. The eligible 76 patients were those with histologically confirmed malignant gliomas, seen at the University of Texas M. D. Anderson Cancer Center between 1994 and 1997, for whom we had sufficient blood for the in vitro gamma-radiation assay. After gamma-irradiation of each subject's lymphocytes, the frank chromatid breaks in 50 metaphases were averaged to calculate breaks/cell. On the basis of our patient series, we established a gamma-ray mutagen sensitivity cutoff point of 0.55 breaks/cell that was confirmed by bootstrap resampling techniques. Patients with values >0.55 breaks/cell were considered sensitive. Kaplan-Meier and Cox proportional hazards modeling were used for the analysis. The gamma-ray mutagen-sensitive patients had worse survival than the nonsensitive patients, with an unadjusted hazard rate ratio of 1.6 (95% confidence interval, 0.9-2.8; P = 0.15). After adjustment for age, tumor histology, and extent of surgical resection, the hazard rate ratio was 2.4 (95% confidence interval, 1.3-4.6; P = 0.0081). Our data suggest that gamma-ray mutagen sensitivity is a prognostic indicator of survival in glioma patients. The significance of these findings needs to be verified in studies with larger samples of patients with histologically similar gliomas.

Incidence of haematopoietic malignancies in US radiologic technologists.

BACKGROUND: There are limited data on risks of haematopoietic malignancies associated with protracted low-to-moderate dose radiation. AIMS: To contribute the first incidence risk estimates for haematopoietic malignancies in relation to work history, procedures, practices, and protective measures in a large population of mostly female medical radiation workers. METHODS: The investigators followed up 71,894 (77.9% female) US radiologic technologists, first certified during 1926-80, from completion of a baseline questionnaire (1983-89) to return of a second questionnaire (1994-98), diagnosis of a first cancer, death, or 31 August 1998 (731,306 person-years), whichever occurred first. Cox proportional hazards regression was used to compute risks. RESULTS: Relative risks (RR) for leukaemias other than chronic lymphocytic leukaemia (non-CLL, 41 cases) were increased among technologists working five or more years before 1950 (RR = 6.6, 95% CI 1.0 to 41.9, based on seven cases) or holding patients 50 or more times for x ray examination (RR = 2.6, 95% CI 1.3 to 5.4). Risks of non-CLL leukaemias were not significantly related to the number of years subjects worked in more recent periods, the year or age first worked, the total years worked, specific procedures or equipment used, or personal radiotherapy. Working as a radiologic technologist was not significantly linked with risk of multiple myeloma (28 cases), non-Hodgkin's lymphoma (118 cases), Hodgkin's lymphoma (31 cases), or chronic lymphocytic leukaemia (23 cases). CONCLUSION: Similar to results for single acute dose and fractionated high dose radiation exposures, there was increased risk for non-CLL leukaemias decades after initial protracted radiation exposure that likely cumulated to low-to-moderate doses.

Lung cancer, smoking patterns, and mutagen sensitivity in Mexican-Americans.

BACKGROUND: Mexican-Americans have lower age-adjusted lung cancer incidence rates than non-Hispanic whites and African-Americans. Since 87% of lung cancers are attributed to tobacco exposure, this difference could be explained partly by lower prevalence of cigarette smoking. However, only a fraction of exposed individuals will develop smoking-related cancer, and genetically determined differences in modulation of environmental exposures could also explain some of this ethnic risk differential in lung cancer incidence in the United States. However, little research on genetic susceptibility has been focused on Hispanic populations in the United States. METHODS: We are conducting a case-control study of lung cancer in a high-risk group (African-Americans) and a low-risk group (Mexican-Americans) to evaluate ethnic differences in mutagen sensitivity by an in vitro assay that quantifies mutagen-induced chromosome breaks in short-term lymphocyte cultures. RESULTS: In the 174 Mexican-Americans (67 lung cancer case patients and 107 control subjects) accrued to date, all measures of cigarette smoking (intensity, duration, nicotine and tar contents, depth of inhalation, and type of cigarette) were significant predictors of lung cancer risk. There were significantly higher risks associated with mutagen sensitivity (defined as > or = 1 break/cell) for both former smokers (odds ratio [OR] = 4.5; 95% confidence interval [CI] = 0.9-21.9) and current smokers (OR = 2.6; 95% CI = 0.6-11.1). Mutagen sensitivity also appeared to be implicated in risk in patients who were less than 55 years old at diagnosis (OR = 15.0; 95% CI = 1.0-228.9) and in those with lower cigarette exposure (OR = 11.0; compared with an OR of 1.7 for the heaviest smokers). The overall OR for mutagen sensitivity adjusted for age, sex, and pack-years of smoking was 2.9 (95% CI = 0.8-9.9). Neither current smoking status nor years of exposure shifted the sensitivity profile of case patients and control subjects. CONCLUSION: Although this study showed higher percentages of nonsmokers among Mexican-Americans than our previously reported data for African-Americans, the Mexican-American case patients were heavier smokers than the African-American case patients. The prevalence of mutagen sensitivity for Mexican-Americans was 64.1% in case patients and 26.2% in control subjects. In African-Americans, mutagen sensitivity was previously reported to be 55.3% in case patients and 24.6% in control subjects. These preliminary data do not support our a priori hypothesis that a lower prevalence of mutagen sensitivity in Mexican-Americans would account for the lower incidence of lung cancer. Mutagen sensitivity, however, is only one of an array of potential susceptibility markers that we are evaluating in this unique population.

Evaluation of sister chromatid exchange and chromosome breaks in a cohort of untreated Hodgkin's disease patients.

Cytogenetic biomarkers, chromosomal breaks [spontaneous breaks (SB) and bleomycin-induced breaks (BIB)], and sister chromatid exchange (SCE) have been shown to be sensitive cytological assays to defect susceptibility to DNA-damaging effects. However, little information is available on how environmental factors and demographic and clinical characteristics influence variation among individuals. We sought to characterize interindividual variability in a cohort of 105 untreated adult Hodgkin's disease patients. SB, BIB, and SCE data were integrated with epidemiological data by using linear regression analysis. Age, sex, ethnicity, education, histology, history of mononucleosis, and family history of cancer showed no association with any biomarker. In univariate analysis, alcohol intake was significantly associated with high SCEs (P = 0.005) and SBs (P = 0.02). Current smoking was associated only with high frequencies of SCE (P = 0.05). Advanced stage of disease was related with high SBs (P = 0.01). BIBs were not associated with any of the variables studied. In multivariate modeling, current alcohol intake was associated with high SCEs (P = 0.04) and SBs (P = 0.01). Former smokers had higher SBs than nonsmokers did (P = 0.02). A small positive correlation was found among each pair of markers. The higher SCEs and SBs in patients who smoke and consume alcohol indicate the need for evaluating these exposures when interpreting these biomarkers.

Gender difference in smoking effect on chromosome sensitivity to gamma radiation in a healthy population.

In the general population, there is variation in radiosensitivity associated with cancer risk. However, data on the role of epigenetic factors in the variation of radiosensitivity are scarce. Thus we investigated the effects of smoking and age on the radiosensitivity of human lymphocytes by measuring the frequency of chromosome aberrations after in vitro exposure to gamma rays in peripheral lymphocytes from 441 healthy subjects (18-95 years old). We analyzed the frequency of both spontaneous (baseline) and in vitro gamma-ray-induced (1.5 Gy) chromatid breaks in 50 well-spread metaphases per subject. The overall mean frequencies of spontaneous and induced breaks were 0.02 and 0.45 per cell, respectively. The mean frequency of induced breaks was significantly higher in men than in women (P = 0.03) but did not differ by age or ethnicity. Donors who had ever smoked showed a small but significantly increased frequency of induced breaks (mean = 0.47) compared to nonsmokers (mean = 0.41; P = 0.005). Further stratification and multivariate analyses revealed that the smoking effect was more pronounced in men than in women. These findings support a smoking effect on radiosensitivity in a healthy population, particularly in men. Therefore, when evaluating the association between radiosensitivity and susceptibility to smoking-related cancers, the effect of smoking should be taken into account.

Three measures of mutagen sensitivity in a cancer-free population.

Different individuals appear to respond differently to the same carcinogen, and different mutagens act differently on cells. We conducted mutagen sensitivity assays by using three mutagens (bleomycin, a radiomimetic agent; 4-nitroquinoline-1-oxide [4-NQO], an ultraviolet light mimetic agent; and benzo[a]pyrene diol epoxide [BPDE], a tobacco mutagen) in parallel in healthy human subjects to determine the relationships among these assays. Our results showed that the mean breaks per cell values (b/c) (+/- SD) for bleomycin, 4-NQO, and BPDE sensitivity were 0.49 (+/- 0.26), 0.53 (+/- 0.30), and 0.66 (+/- 0.41), respectively. Age, sex, smoking status, and family history of cancer were not correlated with any of these mutagen sensitivities. Also, there was no correlation between bleomycin and 4-NQO or 4-NQO and BPDE sensitivity, but a weak correlation between bleomycin and BPDE was observed (correlation coefficient = 0.289; P = 0.001). When the 75th percentile of b/c was used as a cutoff point in each assay, only one individual (1.8%) was sensitive to all three mutagens. Ten individuals (17.9%) were sensitive to two mutagens, 20 (35.7%) to one mutagen, and 25 (44.6%) to none of three mutagens. Our study suggests that these three mutagens may involve different DNA damage and repair pathways. The lack of correlation between the assay results may indicate the necessity of using a battery of mutagen sensitivity tests to refine our ability to identify a subpopulation at high cancer risk.

Chromosome breaks and sister chromatid exchange as predictors of second cancers in Hodgkin's disease.

Hodgkin's disease (HD) survivors face an increased risk of developing second cancers. We evaluated baseline cytogenetic biomarkers, sister chromatid exchange (SCE) and chromosome breaks [spontaneous (SCB) and bleomycin-induced (BIB)], as predictors of second cancer risk in a cohort of 105 adult HD patients. During follow-up, seven second cancers occurred. SCBs and BIBs showed no association with risk of second primaries. Multivariate Cox regression revealed that high levels of SCEs (relative risk (RR)=11.3, p=0.02) and age (RR=1.08, p=0.02) predicted second cancer risk. Histology, stage, and treatment were not associated with elevated risk. In conclusion, baseline SCE frequencies may be a useful biomarker for identifying HD patients at increased risk of developing second cancers. These results need to be verified in a larger cohort with a longer follow-up time.

Risk assessment for developing gliomas: a comparison of two cytogenetic approaches.

Chromosome instability (CIN) measured as chromosome aberrations has long been suggested as a cancer susceptibility biomarker. Conventional cytogenetic end-points are now being improved by combining molecular methods, which increases the sensitivity, specificity, and precision of the assay. In this study we examined both spontaneous and gamma-ray induced CIN in lymphocyte cultures from 51 previously untreated glioma patients and 51 age-, sex- and ethnicity-matched controls. CIN was assessed using two parallel methods: (1) the mutagen sensitivity (MS) assay and (2) the multicolor fluorescence in situ hybridization (FISH) assay. The frequency of spontaneous breaks was significantly higher in glioma patients (mean+/-S.D., 2.12+/-1.07) than in controls (1.24+/-0.86, P<0.001) when using the FISH assay but not the MS assay (0.019+/-0.02 and 0.019+/-0.01, respectively; P=0.915). Similarly, the frequency of induced chromatid breaks was significantly higher using the FISH assay (3.39+/-1.72) but not the MS assay (0.42+/-0.16) in the patients versus controls (2.08+/-1.18 and 0.37+/-0.15, respectively; P<0.001 and P=0.10, respectively). By using the median number of breaks in the controls as the cutoff value, we observed an odds ratio (ORs) of 5.13 (95% CI=2.23-12.1) for spontaneous and 4.86 (95% CI=2.08-11.4) for induced CIN using the FISH assay, whereas the ORs were 1.32 (95% CI=0.49-3.58) and 1.28 (95% CI=0.59-2.80) for spontaneous and induced CIN using the MS assay. There was also a significant increase in the frequency of hyperdiploid cells in the glioma cases which could only be detected using the FISH assay (OR=4.0, 95% CL=0.9-17.0). By combining both methods an estimated risk of 7.0 (95% CI=1.7-25.6) was observed. There was no correlation between the breaks detected by the two methods suggesting that each method is a measure of a different event. The results indicate that using the multicolor FISH assay for detection of CIN in peripheral blood lymphocytes in glioma patients is a more useful marker for risk assessment.

Cancer mortality among petroleum refinery and chemical manufacturing workers in Texas.

Epidemiologic historical cohort studies of petroleum refinery and chemical manufacturing workers in Texas were reviewed to examine their cancer mortality in comparison to the U.S. and to assess the possible impact of cancer mortality among these workers on the State of Texas as a whole. Summary standardized mortality ratios and 95% confidence intervals were calculated for 20 cancer types, taking into account the heterogeneity of individual studies. There were 4314 cancer deaths among the 92,318 workers employed in 10 independent plant populations. Overall, there was a significant deficit in cancer mortality among petrochemical workers compared with the general U.S. population (SMR = 88, 95% CI = 80 to 96). Only the summary SMRs for brain cancer (SMR = 113, 95% CI = 96 to 133) and leukemias (SMR = 112, 95% CI = 94 to 130) approached statistical significance. Lung and liver cancer mortality excesses, noted for Texas as a whole, were decreased in these workers. Additional follow-up of these cohorts, their expansion to include minority and female workers, and additional study of possible occupational contributions to leukemia and brain cancer are recommended.

Cosmetic saline breast implants: a survey of satisfaction, breast-feeding experience, cancer screening, and health.

Saline breast implants have been used for the past 30 years for cosmetic and reconstructive purposes. Data based on a large number of patients are needed to evaluate patient satisfaction, cancer screening practices, problems associated with breast-feeding, and health effects. We conducted a follow-up study of 292 cosmetic saline breast implant patients from Texas and Louisiana who consented to a telephone interview. Using a Likert scale, we measured the patients' degree of satisfaction with the implants. The results indicated that 80.5 percent were satisfied, 73.3 percent would recommend saline breast implants to others, and 65.1 percent felt that implants improved their quality of life. The extent of satisfaction was independent of the number of additional surgeries, age at implant, and follow-up time. Mammography use and breast self-examination were reported with high frequency in this survey. Ninety-one percent of study participants who were between 40 and 49 years of age at time of interview and 94 percent of those 50 or older reported having had at least one mammogram. Breast self-examination was practiced by 75 percent of the women, and 61 percent reported checking their breasts at least once a month. Of the 46 women who had children after augmentation, 28 reported breast-feeding and 8 (28.6 percent) reported having implant-related problems. The patients were asked to provide information regarding a series of conditions for which they sought medical attention. They reported: atypical rheumatoid syndrome (n = 1), Sjögren syndrome (n = 1), atypical autoimmune disorder (n = 1), and chronic fatigue syndrome (n = 2). Overall, women who elected to have saline breast implants were satisfied with their augmentations, had mammograms and performed breast self-examinations more often than nonaugmented women. A few had problems when breast-feeding that could be related to their implants. There were no reports of breast cancer, but five women reported autoimmune conditions.

Genetic predisposition to radiation-related cancer and potential implications for risk assessment.

Several lines of evidence suggest that risk estimates for cancer associated with radiation exposure incorporate individuals who are more and less inherently susceptible to the carcinogenic effects of radiation, and the technology to further evaluate this issue is now available. For example, genome-wide association scan studies could be undertaken to address, at least in part, the direction of causality in the observations of differential sensitivity to radiomimetic agents in cancer cases compared with normal individuals, thereby building on previous observations that sensitivity to these agents is higher in apparently normal individuals carrying gene mutations in NBS and ATM. Direct studies of risk of second cancers in relation to radiation are underway, and some results have been reported (e.g. for the PRDM1 gene as related to sensitivity to radiation-related cancers after treatment for Hodgkin's lymphoma). It is important to understand the risk synergies between variants affecting associations with various cancers defining susceptibility in unexposed populations and the excess risk in populations therapeutically or occupationally exposed to radiation for the purpose of risk protection, especially as additional baseline risk variants are discovered in increasingly large-scale analyses. While there are studies that are beginning to address these questions, there have been no compelling new discoveries, to date, to indicate that predisposition information should be included in risk assessment. The conclusions in ICRP Publications 79 and 103 appear relevant today.

Hormonal and reproductive factors and risk of postmenopausal thyroid cancer in the NIH-AARP Diet and Health Study.

BACKGROUND: Worldwide, thyroid cancer incidence rates are higher among women than men. While this suggests a possible etiologic role of female sex hormones, clear associations between hormonal and reproductive factors and thyroid cancer have not been observed. However, few large prospective studies have been conducted. METHODS: Hazard ratios (HRs) and 95% confidence intervals (CIs) for hormonal and reproductive factors and incident thyroid cancer were estimated using Cox regression methods in the prospective US NIH-AARP Diet and Health Study. Between 1995 and 2006, 312 first primary incident thyroid cancers were diagnosed among 187,865 postmenopausal women ages 50-71 at baseline. RESULTS: Thyroid cancer was not associated with ages at menarche or menopause, menopause type, or parity. Oral contraceptive use for ≥10 years (vs. never use) was inversely associated with thyroid cancer risk (HR, 0.48; 95%CI, 0.28-0.84; P(trend)=0.01). Women who reported current menopausal hormone therapy at baseline had an increased thyroid cancer risk vs. never users (HR 1.38; 95% CI: 1.07-1.79) but there was no trend with increasing duration of use. Women with benign breast disease (BBD) had a significantly higher thyroid cancer risk vs. women without BBD (HR, 1.47; 95% CI, 1.09-1.99). CONCLUSIONS: Our results do not support a strong role for female hormonal and reproductive factors including ages at menarche and menopause, type of menopause or parity, in thyroid cancer etiology among postmenopausal women. Compared with previous studies, no clear patterns emerge for exogenous hormone use but further analysis in large, prospective populations may be informative. The HR for BBD is consistent with the one previous prospective analysis that examined this association.