IGF1 genotype, mean plasma level and breast cancer risk in the Hawaii/Los Angeles multiethnic cohort

The insulin-like growth factor 1 gene (IGF1) is a strong candidate gene for a breast cancer susceptibility model. We investigated a dinucleotide repeat 969 bp upstream from the transcription start site of the IGF1 gene for possible associations with plasma IGF1 levels and breast cancer risk in a multiethnic group of postmenopausal women. Furthermore, we investigated the relation between race/ethnicity, mean plasma IGF1 levels and breast cancer rates in the Hawaii/Los Angeles Multiethnic Cohort. The mean age-adjusted IGF1 level among Latino-American women, 116 ng ml(-1), was statistically significantly lower than the mean age-adjusted IGF1 levels for each of the three other racial/ethnic groups, African-American, Japanese-American and Non-Latino White women (146, 144 and 145 ng ml(-1), respectively) (P<0.0001). Latino-American women have the lowest breast cancer rates of any racial/ethnic group in the cohort. These results support the investigation of an expansion of the hypothesis for an important role of IGF1 in breast cancer tumorigenesis to different racial/ethnic groups and to postmenopausal women. It is unlikely that any involvement of IGF1 in breast cancer aetiology is mediated by the IGF1 dinucleotide repeat polymorphism, which was not significantly associated with circulating IGF1 levels nor breast cancer risk in this study. Research into relevant determinants of IGF1 levels in the blood must continue

Prediagnostic sex steroid hormones in relation to male breast cancer risk

Purpose Although previous studies have implicated a variety of hormone-related risk factors in the etiology of male breast cancers, no previous studies have examined the effects of endogenous hormones. Patients and Methods Within the Male Breast Cancer Pooling Project, an international consortium comprising 21 case-control and cohort investigations, a subset of seven prospective cohort studies were able to contribute prediagnostic serum or plasma samples for hormone quantitation. Using a nested case-control design, multivariable unconditional logistic regression analyses estimated odds ratios and 95% CIs for associations between male breast cancer risk and 11 individual estrogens and androgens, as well as selected ratios of these analytes. Results Data from 101 cases and 217 matched controls were analyzed. After adjustment for age and date of blood draw, race, and body mass index, androgens were found to be largely unrelated to risk, but circulating estradiol levels showed a significant association. Men in the highest quartile had an odds ratio of 2.47 (95% CI, 1.10 to 5.58) compared with those in the lowest quartile (trend P = .06). Assessment of estradiol as a ratio to various individual androgens or sum of androgens showed no further enhancement of risk. These relations were not significantly modified by either age or body mass index, although estradiol was slightly more strongly related to breast cancers occurring among younger (age < 67 years) than older men. Conclusion Our results support the notion of an important role for estradiol in the etiology of male breast cancers, similar to female breast cancers

Plasma carotenoids, retinol, and tocopherols and postmenopausal breast cancer risk in the Multiethnic Cohort Study: a nested case-control study

Assessments by the handful of prospective studies of the association of serum antioxidants and breast cancer risk have yielded inconsistent results. This multiethnic nested case-control study sought to examine the association of plasma carotenoids, retinol, and tocopherols with postmenopausal breast cancer risk.From the biospecimen subcohort of the Multiethnic Cohort Study, 286 incident postmenopausal breast cancer cases were matched to 535 controls on age, sex, ethnicity, study location (Hawaii or California), smoking status, date/time of collection and hours of fasting. We measured prediagnostic circulating levels of individual carotenoids, retinol, and tocopherols. Conditional logistic regression was used to compute odds ratios and 95% confidence intervals.Women with breast cancer tended to have lower levels of plasma carotenoids and tocopherols than matched controls, but the differences were not large or statistically significant and the trends were not monotonic. No association was seen with retinol. A sensitivity analysis excluding cases diagnosed within 1 year after blood draw did not alter the findings.The lack of significant associations in this multiethnic population is consistent with previously observed results from less racially-diverse cohorts and serves as further evidence against a causal link between plasma micronutrient concentrations and postmenopausal breast cancer risk

Ethnicity coding in a regional cancer registry and in Hospital Episode Statistics

BACKGROUND: The collection of ethnicity information as part of cancer datasets is important for planning services and ensuring equal access, and for epidemiological studies. However, ethnicity has generally not been well recorded in cancer registries in the UK. The aim of this study was to determine the completeness of ethnicity coding in the Thames Cancer Registry (TCR) database and within the Hospital Episode Statistics (HES) data as held by the London Health Observatory, and to investigate factors associated with ethnicity being recorded. METHODS: Records for 111821 hospital admissions of London residents with a malignant cancer as a primary diagnosis between April 2002 and March 2003 and records for 25581 London residents diagnosed with cancer in 2002 were examined. Data on sex, age, cancer network of residence, deprivation, proportion of non-whites in the local authority population, and site of cancer were available. The proportion of patients in each group with a valid ethnicity code was calculated. In the TCR data proportions were also calculated adjusted for all other variables. RESULTS: Ethnicity was recorded for 90661 (81.1%) of the hospital admissions in the HES data and 5796 (22.7%) patients on the TCR database. Patients resident in areas with a higher proportion of non-white residents and the most deprived populations were more likely to have an ethnic code on the TCR database, though this pattern was not seen in the HES data. Adjustment did not materially affect the association between deprivation and ethnicity being recorded in the TCR data. CONCLUSION: There was a large difference in completeness of ethnicity between the data sources. In order to improve the level of recording in TCR data there needs to be better recording of ethnicity in sources TCR data collection staff have access to, or use of information from other sources e.g. electronic data feeds from hospitals or pathology laboratories, or HES data itself supplied directly to TCR. Efforts to collect ethnicity data should be encouraged in all healthcare settings. Future research should explore where the difficulties collecting ethnicity information lie, whether with patients, healthcare professionals or the recording procedure, and how such problems can be overcome

The association of mammographic density with ductal carcinoma in situ of the breast: the Multiethnic Cohort

INTRODUCTION: It is well established that women with high mammographic density are at greater risk for breast cancer than are women with low breast density. However, little research has been done on mammographic density and ductal carcinoma in situ (DCIS) of the breast, which is thought to be a precursor lesion to some invasive breast cancers. METHOD: We conducted a nested case-control study within the Multiethnic Cohort, and compared the mammographic densities of 482 patients with invasive breast cancer and 119 with breast DCIS cases versus those of 667 cancer-free control subjects. A reader blinded to disease status performed computer-assisted density assessment. For women with more than one mammogram, mean density values were computed. Polytomous logistic regression models were used to compute adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for two measurements of mammographic density: percentage density and dense area. RESULTS: Mammographic density was associated with invasive breast cancer and breast DCIS. For the highest category of percentage breast density (≥50%) as compared with the lowest (<10%), the OR was 3.58 (95% CI 2.26–5.66) for invasive breast cancer and 2.86 (1.38–5.94) for breast DCIS. Similarly, for the highest category of dense area (≥45 cm(2)) as compared with the lowest (<15 cm(2)), the OR was 2.92 (95% CI 2.01–4.25) for invasive breast cancer and 2.59 (1.39–4.82) for breast DCIS. Trend tests were significant for invasive breast cancer (P for trend < 0.0001) and breast DCIS (P for trend < 0.001) for both percentage density and dense area. CONCLUSION: The similar strength of association for mammographic density with breast DCIS and invasive breast cancer supports the hypothesis that both diseases may have a common etiology

Intakes of fruits and vegetables, carotenoids and vitamins A, E, C in relation to the risk of bladder cancer in the ATBC cohort study

We examined the relation between dietary fruit and vegetables, carotenoids and vitamin intakes and the risk of bladder cancer among male smokers in a prospective cohort study. Over a median of 11 years, we followed 27 111 male smokers aged 50–69 years who were initially enrolled in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study. During this period, 344 men developed bladder cancer. All of these men had completed a 276-food item dietary questionnaire at baseline. Cox proportional hazards models were used to estimate the relative risks and 95% confidence intervals and to simultaneously adjust for age, smoking history, energy intake and intervention group. Consumption of fruits and vegetables was not associated with the risk of bladder cancer (relative risk=1.28; 95% confidence intervals CI: 0.89–1.84, for highest vs lowest quintile). Similarly, no associations were observed for groups of fruits or vegetables (berries and cruciferous vegetables), or for specific fruits and vegetables. Dietary intakes of alpha-carotene, beta-carotene, lycopene, lutein/zeaxanthin, beta-cryptoxanthin, vitamins A, E, and C, and folate were not related to the risk of bladder cancer. These findings suggest that fruit and vegetable intakes are not likely to be associated with bladder cancer risk. However, these results may not be generalisable to non-smokers

Benign thyroid disease and dietary factors in thyroid cancer: a case-control study in Kuwait

We conducted a population-based study of 313 case–control pairs in Kuwait to examine the aetiology of thyroid cancer, the second most common neoplasm among women in this and several other countries in the Gulf region. Among the demographic variables, individuals with 12+ years of education had a significantly reduced risk of thyroid cancer (OR=0.6; 95% CI: 0.3–0.9). The average age at diagnosis (s.d.) of thyroid cancer was 34.711 years in women and 3913.4 years in men. History of thyroid nodule was reported only by cases (n=34; 10.9%; lower 95% CI: 12.0); and goitre by 21 cases and four controls (OR=5.3; 95% CI: 1.8–15.3). There was no significant increase in risk with history of hypothyroidism (OR=1.8) or hyperthyroidism (OR=1.7). For any benign thyroid disease, the OR was 6.4 (95% CI: 3.4–12.0); and the population attributable risk was about 26% (95% CI: 21.1–30.9). Stepwise regression analysis showed that high consumption of processed fish products (OR=2.2; 95% CI: 1.6–3.0) fresh fish (OR=0.5; 95% CI: 0.4–0.7) and chicken (OR=1.7; 95% CI: 1.2–2.3) were independently associated with thyroid cancer with significant dose-response relationships. Among the thyroid cancer patients who reported high consumption of fish products, a large majority also reported high consumption of fresh fish (98%) and shellfish (68%). No clear association emerged with consumption of cruciferous vegetables. These data support the hypothesis that hyperplastic thyroid disease is strongly related to thyroid cancer; and that habitual high consumption of various seafoods may be relevant to the aetiology of thyroid cancer. The association with chicken consumption requires further study

Consistent Association of Type 2 Diabetes Risk Variants Found in Europeans in Diverse Racial and Ethnic Groups

It has been recently hypothesized that many of the signals detected in genome-wide association studies (GWAS) to T2D and other diseases, despite being observed to common variants, might in fact result from causal mutations that are rare. One prediction of this hypothesis is that the allelic associations should be population-specific, as the causal mutations arose after the migrations that established different populations around the world. We selected 19 common variants found to be reproducibly associated to T2D risk in European populations and studied them in a large multiethnic case-control study (6,142 cases and 7,403 controls) among men and women from 5 racial/ethnic groups (European Americans, African Americans, Latinos, Japanese Americans, and Native Hawaiians). In analysis pooled across ethnic groups, the allelic associations were in the same direction as the original report for all 19 variants, and 14 of the 19 were significantly associated with risk. In summing the number of risk alleles for each individual, the per-allele associations were highly statistically significant (P<10−4) and similar in all populations (odds ratios 1.09–1.12) except in Japanese Americans the estimated effect per allele was larger than in the other populations (1.20; Phet = 3.8×10−4). We did not observe ethnic differences in the distribution of risk that would explain the increased prevalence of type 2 diabetes in these groups as compared to European Americans. The consistency of allelic associations in diverse racial/ethnic groups is not predicted under the hypothesis of Goldstein regarding “synthetic associations” of rare mutations in T2D