Radiotherapy did not increase thyroid cancer risk among women with breast cancer: A nationwide population‐based cohort study

The aim of this study was to evaluate whether an increased risk of thyroid cancer exists among women with breast cancer in Taiwan, particularly among those receiving RT. We used data from the National Health Insurance system of Taiwan for the investigation. The breast cancer cohort contained 55,318 women (including 28,187 who received RT and 27,131 who received no RT), each of whom was randomly frequency matched according to age and index year with three women without breast cancer from the general population. Cox's proportion hazards regression analysis was conducted to estimate the effects of breast cancer with or without RT treatment on subsequent thyroid cancer risk. We found that women with breast cancer exhibited a significantly higher risk of subsequent thyroid cancer (adjusted hazard ratio [aHR] = 1.98, 95% confidence interval [CI] = 1.60–2.44). The two groups (with or without RT) in the breast cancer cohort exhibited significantly increased risks. However, in the breast cancer cohort, the risk of thyroid cancer among women who received RT was not significantly higher than that of women who received no RT (aHR = 1.28, 95% CI = 0.90–1.83). Stratified analysis according to age revealed that only younger women with breast cancer (20–54 y) had a significantly higher risk of developing thyroid cancer. This study determined that Taiwanese women with breast cancer had a higher risk of developing thyroid cancer; however, RT seems to not play a crucial role in this possible relationship.     

Cancer survival in China, 2003–2005: A population‐based study

Limited population‐based cancer registry data available in China until now has hampered efforts to inform cancer control policy. Following extensive efforts to improve the systematic cancer surveillance in this country, we report on the largest pooled analysis of cancer survival data in China to date. Of 21 population‐based cancer registries, data from 17 registries (n = 138,852 cancer records) were included in the final analysis. Cases were diagnosed in 2003–2005 and followed until the end of 2010. Age‐standardized relative survival was calculated using region‐specific life tables for all cancers combined and 26 individual cancers. Estimates were further stratified by sex and geographical area. The age‐standardized 5‐year relative survival for all cancers was 30.9% (95% confidence intervals : 30.6%‐31.2%). Female breast cancer had high survival (73.0%) followed by cancers of the colorectum (47.2%), stomach (27.4%), esophagus (20.9%), with lung and liver cancer having poor survival (16.1% and 10.1%), respectively. Survival for women was generally higher than for men. Survival for rural patients was about half that of their urban counterparts for all cancers combined (21.8% vs. 39.5%); the pattern was similar for individual major cancers except esophageal cancer. The poor population survival rates in China emphasize the urgent need for government policy changes and investment to improve health services. While the causes for the striking urban‐rural disparities observed are not fully understood, increasing access of health service in rural areas and providing basic health‐care to the disadvantaged populations will be essential for reducing this disparity in the future.     

Childhood cancer incidence and survival in Japan and England: A population‐based study (1993‐2010)

The present study aimed to compare cancer incidence and trends in survival for children diagnosed in Japan and England, using population‐based cancer registry data. The analysis was based on 5192 children with cancer (age 0‐14 years) from 6 prefectural cancer registries in Japan and 21 295 children diagnosed in England during 1993‐2010. Differences in incidence rates between the 2 countries were measured with Poisson regression models. Overall survival was estimated using the Kaplan–Meier method. Incidence rates for Hodgkin lymphoma, renal tumors and Ewing sarcomas in England were more than twice as high as those in Japan. Incidence of germ cell tumors, hepatic tumors, neuroblastoma and acute myeloid leukemia (AML) was higher in Japan than in England. Incidence of all cancers combined decreased in Japan throughout the period 1993 to 2010, which was mainly explained by a decrease in registration of neuroblastoma in infants. For many cancers, 5‐year survival improved in both countries. The improvement in survival in chronic myeloid leukemia (CML) was particularly dramatic in both countries. However, 5‐year survival remained less than 80% in 2005‐2008 in both countries for AML, brain tumors, soft tissue sarcomas, malignant bone tumors and neuroblastoma (age 1‐14 years). There were significant differences in incidence of several cancers between countries, suggesting variation in genetic susceptibility and possibly environmental factors. The decrease in incidence for all cancers combined in Japan was related to the cessation of the national screening program for neuroblastoma. The large improvement in survival in CML coincided with the introduction of effective therapy (imatinib).     

Cancer risk in long‐term users of vitamin K antagonists: A population‐based case–control study

Some evidence suggests that long‐term use of vitamin K antagonists (VKAs) has a cancer chemopreventive effect. Such an effect would have considerable implications in terms of understanding tumor biology. To evaluate if long‐term VKA treatment influences the risk of developing cancer, we performed a matched case–control analysis. We used data from four Danish nationwide registers. Cases were all Danish individuals with a first‐time cancer diagnosis (except nonmelanoma skin cancer) between 2000 and 2009. For each case, eight controls, matched by birth year and gender, were selected from the source population by risk‐set sampling. Long‐term VKA use was defined as exposure to VKA for a period of 3 or more years. Conditional logistic regression was used to compute odds ratios (ORs) for cancer associated with long‐term VKA exposure, adjusting for potential confounders. Prespecified subanalyses were performed for selected cancer sites, subgroups and measures of exposure. A total of 238,196 cases and 1,713,176 controls were included. The adjusted OR for cancer associated with long‐term VKA exposure was 0.99 (95% CI: 0.95–1.02). Long‐term VKA use was associated with increased ORs for alcohol‐ or obesity‐related cancer sites, whereas we observed a decreased risk of prostate cancer (OR: 0.86; 95% CI: 0.78–0.95). Our study does not support a general chemopreventive effect of VKA drugs. However, in accordance with findings from previous studies, we found an inverse association between use of VKA and prostate cancer.     

Increased risk of cancer in patients with early‐onset cataracts: A nationwide population‐based study

Early‐onset cataracts are associated with insufficient antioxidative activity, and, therefore, a potential risk of cancer. This study investigated the risk of cancer after being diagnosed with early‐onset cataracts. Retrospective claims data from the Taiwan National Health Insurance Research Database were analyzed. Study subjects were comprised of patients with early‐onset cataracts, aged 20–55 years (International Classification of Diseases, 9th Revision, Clinical Modification [ICD‐9‐CM] code 366.00, 366.01, 366.02, 366.03, 366.04, 366.09, 366.17 and 366.18) and newly diagnosed between 1997 and 2010 (n = 1281), and a comparison cohort without the disease (n = 5124). Both cohorts were followed up until 2010 to estimate the incidences of cancer. We used the Poisson regression model to compare incidence rate ratios and the 95% confidence interval (CI). Cox proportional hazards regression was used to assess the hazard ratio (HR) of cancer associated with early‐onset cataracts. The overall incidence rate of all cancers was 2.19‐fold higher in the early‐onset cataract cohort than in the comparison cohort (8.06 vs 3.68 per 1000 person‐years) with an adjusted HR of 2.13 (95% CI = 1.48, 3.07). The site‐specific analysis also showed a strong relationship, with adjusted HR of 3.24 ((95% CI = 1.30, 8.10) for head and neck cancer, 3.29 (95% CI 1.16, 9.31) for hepatoma and 3.19 (95% CI 1.34, 7.58) for breast cancer. The present study suggests that patients with early‐onset cataracts are at an increased risk of being diagnosed with cancer in subsequent years.     

Diabetes in midlife and risk of cancer in late life: A nationwide Swedish twin study

The association between diabetes and cancer risk remains controversial. Hence, we examined whether midlife diabetes is related to the risk of cancer in late‐life, and whether genetic and early‐life environmental factors play a role in this association. This study included 25,154 twin individuals born in 1958 or earlier from the Swedish Twin Registry. Information on cancer diagnosis in late life (aged ≥ 65) during 1998–2014, was derived from the National Patient and Cancer Registries. Diabetes was ascertained based on self‐ or informant‐reported history, patient registry and antidiabetic medication use. Midlife diabetes was defined when diabetes was diagnosed before 65 years. Data were analyzed following two strategies: (i) unmatched case‐control analysis for all participants using generalized estimating equation (GEE) models, and (ii) co‐twin control analysis for cancer‐discordant twin pairs using conditional logistic regression. Overall, 1,766 (7.0%) had midlife diabetes and 5,293 (21.0%) had cancer in late‐life. In multiadjusted GEE models, the odds ratios (95% CIs) of diabetes were 10.55 (2.95–37.67) for pharynx cancer, 5.78 (1.72–19.40) for small intestine cancer, 2.37 (1.14–4.91) for liver cancer and 0.48 (0.35–0.67) for prostate cancer. In people with diabetes, diabetes duration was dose‐dependently associated with cancer risk. In conditional logistic regression analysis of 176 prostate cancer‐discordant twin pairs, the association between midlife diabetes and prostate cancer in later life became stronger. Midlife diabetes increases the risk of pharynx, small intestine and liver cancers, but reduces prostate cancer risk in late life. Genetic and early‐life environmental factors may partially contribute to the diabetes–prostate cancer association.     

Incident cancer risk after the start of aspirin use: Results from a Dutch population‐based cohort study of low dose aspirin users

Observational and intervention studies suggest that low dose aspirin use may prevent cancer. The objective of this study was to investigate the protective effect of long term low dose aspirin use (≤100 mg daily) on cancer in general and site‐specific cancer among low dose aspirin users in the Dutch general population. We conducted a population‐based cohort study with detailed information on aspirin exposure and cancer incidence. Only incident (new) low dose aspirin users, who were included in the linkage between PHARMO and the Eindhoven Cancer Registry (1998–2010) and free of cancer before the start of follow up were included. A Cox proportional hazard model with cumulative aspirin use as a time‐varying determinant was used to obtain hazard ratios (HR). Duration of aspirin use amongst 109,276 incident low dose aspirin users was not associated with a decreased risk of any of the site‐specific cancers or cancer in general (adjusted HR per year of aspirin use for all cancers: 1.02, 95% confidence interval [CI] 1.00–1.04, HR of >6 years aspirin use compared to <2 years: 1.17, 95% CI 1.02–1.34). After adjusting for current and past aspirin use, 2–6 years of low dose aspirin use was associated with a reduced colorectal cancer risk compared to <2 years of aspirin use (adjusted HR 0.75, 95% CI 0.59–0.96). However, a clear dose‐response relationship was not observed (adjusted HR >6 years aspirin use 0.95, 95% CI 0.60–1.49). Our results do not support the primary prevention of cancer among long term aspirin users.     

Lung cancer mortality risk among breast cancer patients treated with anti-estrogens

BACKGROUND:

The Women's Health Initiative randomized clinical trial reported that menopausal hormone therapy increases lung cancer mortality risk. If this is true, use of anti‐estrogens should be associated with decreased lung cancer mortality risk. The authors compared lung cancer incidence and mortality among breast cancer patients with and without anti‐estrogen therapy.

METHODS:

Our study included all 6655 women diagnosed with breast cancer between 1980 and 2003 and registered at the Geneva Cancer Registry. Among these women, 46% (3066) received anti‐estrogens. All women were followed for occurrence and death from lung cancer until December 2007. The authors compared incidence and mortality rates among patients with and without anti‐estrogens with those expected in the general population by Standardized Incidence Ratios (SIRs) and Standardized Mortality Ratios (SMRs).

RESULTS:

After a total of 57,257 person‐years, 40 women developed lung cancer. SIRs for lung cancer were not significantly decreased among breast cancer patients with and without anti‐estrogens (0.63, 95% confidence intervals [CI], 0.33‐1.10; and 1.12, 95% CI, 0.74‐1.62, respectively) while SMR was decreased among women with anti‐estrogens (0.13, 95% CI, 0.02‐0.47, P<.001) but not for women without anti‐estrogens (0.76, 95% CI, 0.43‐1.23).

CONCLUSIONS:

Compared with expected outcomes in the general population, breast cancer patients receiving anti‐estrogen treatment for breast cancer had lower lung cancer mortality. This study further supports the hypothesis that estrogen therapy modifies lung cancer prognosis. Cancer 2011. © 2011 American Cancer Society.     

Risk of skin cancer and other malignancies in kidney,liver, heart and lung transplant recipients 1970 to 2008—A Swedish population‐based study

Organ transplant recipients are at increased risk of a wide range of malignancies, especially cutaneous squamous cell carcinomas (SCC). Few previous population‐based studies have quantified and compared cancer risks according to graft type and with long‐term follow‐up. Using nationwide Swedish registers, we identified 10,476 recipients transplanted from 1970 to 2008 and followed them for cancer occurrence. Relative risks of cancer in comparison with the general population were expressed as standardized incidence ratios (SIR) and within the transplanted cohort as incidence rate ratios (IRR). During a total follow‐up of 93,432 person‐years, patients were diagnosed with 1,175 cancers excluding SCC, and with 2,231 SCC, SIR_{cancer excl SCC} 2.4 (95% CI, 2.2–2.5); SIR_SCC 121 (95% CI, 116–127). Cancer risks were most increased among heart and/or lung recipients SIR_{cancer excl SCC} 3.3 (95% CI, 2.8–4.0); SIR_SCC 198 (95% CI, 174–224), followed by kidney SIR_{cancer excl SCC} 2.3 (95% CI, 2.1–2.4); SIR_SCC 121 (95% CI, 116–127) and liver recipients SIR_{cancer excl SCC} 2.3 (95% CI, 1.9–2.8); SIR_SCC 32 (95% CI, 24–42). During follow‐up, risk of cancer excluding SCC remained stable while risk of SCC tripled over 20 years irrespective of graft type, partly due to a subgroup of patients developing new SCCs at a rapidly increasing rate. In summary, post‐transplant cancer risk varied by transplanted organ and by cancer site, with the bulk of the excess risk driven by an exceptionally high and accelerating risk of SCC. These findings underscore the importance of regular skin screening in organ transplant recipients.     

Design considerations for identifying breast cancer risk factors in a population‐based study in Africa

Although breast cancer is becoming more prevalent in Africa, few epidemiologic studies have been undertaken and appropriate methodologic approaches remain uncertain. We therefore conducted a population‐based case–control study in Accra and Kumasi, Ghana, enrolling 2,202 women with lesions suspicious for breast cancer and 2,161 population controls. Biopsy tissue for cases prior to neoadjuvant therapy (if given), blood, saliva and fecal samples were sought for study subjects. Response rates, risk factor prevalences and odds ratios for established breast cancer risk factors were calculated. A total of 54.5% of the recruited cases were diagnosed with malignancies, 36.0% with benign conditions and 9.5% with indeterminate diagnoses. Response rates to interviews were 99.2% in cases and 91.9% in controls, with the vast majority of interviewed subjects providing saliva (97.9% in cases vs. 98.8% in controls) and blood (91.8% vs. 82.5%) samples; lower proportions (58.1% vs. 46.1%) provided fecal samples. While risk factor prevalences were unique as compared to women in other countries (e.g., less education, higher parity), cancer risk factors resembled patterns identified elsewhere (elevated risks associated with higher levels of education, familial histories of breast cancer, low parity and larger body sizes). Subjects with benign conditions were younger and exhibited higher socioeconomic profiles (e.g., higher education and lower parity) than those with malignancies, suggesting selective referral influences. While further defining breast cancer risk factors in Africa, this study showed that successful population‐based interdisciplinary studies of cancer in Africa are possible but require close attention to diagnostic referral biases and standardized and documented approaches for high‐quality data collection, including biospecimens.     

Social inequality in cancer survivors’ health behaviours—A Danish population‐based study

The aim of this study was to compare health behaviours (smoking, alcohol consumption, physical activity and diet), to explore social inequality in these behaviours among cancer survivors and individuals with no history of cancer, respectively, and to study the impact of time since diagnosis on cancer survivors’ health behaviours. Data from the Danish National Health Survey from 2013 were linked with data from the Danish Cancer Registry to identify all cancer diagnoses among the respondents during the period 1945–2012. In total, 11,166 cancer survivors and 151,117 individuals with no history of cancer were included. Cancer survivors smoked less and had a more sedentary lifestyle than individuals with no history of cancer. In relation to alcohol and dietary habits, no differences were found between the groups. Wide variations in health behaviours were seen across cancer sites, and in particular lung, bladder and oral cancer survivors had poor health behaviours. We found a clear social gradient in cancer survivors’ health behaviours which reveals the need for greater focus on socially differentiated initiatives within prevention and patient education for cancer survivors. Our study revealed rather blurred results in relation to identifying the optimal timing for health‐related behavioural interventions in cancer survivors.     

Frequency of surveillance computed tomography in non‐Hodgkin lymphoma and the risk of secondary primary malignancies: A nationwide population‐based study

With increasing usage of computed tomography (CT) for lymphoma patients receiving curative‐intent treatment, development of secondary primary malignancy (SPM) related to radiation from CT scans becomes an emerging issue in these long‐term survivors. We conducted a nationwide population‐based study analyzing non‐Hodgkin lymphoma (NHL) patients receiving curative‐intent treatment between January 1997 and December 2010. Patients were divided into two populations by the medium number of CT performed. The cumulative incidence of SPM in these two groups was compared using the Kaplan–Meier method. Propensity score matching was applied to eliminate potential confounders. Group stratification and multivariate analyses calculated by Cox proportional hazard models using competing risk analyses adjusted for mortality were performed to identify independent predictors for SPM. Patients receiving > 8 CT scans had a significantly greater risk for developing SPM (hazard ratio [HR] 2.25, 95% confidence interval [CI] 1.61–3.13; p < 0.001) than those with ≤8 scans and this difference remained significant even after correction with propensity score matching. Among the 180 SPM identified, those receiving more CT scans had significantly higher SPM incidence in cancers of the breast (HR 11.22), stomach (HR 5.22) and liver and biliary tract (HR 2.18) in comparison to those with less exposure. The risk of SPM was estimated to increase 3% per one more CT scan performed. Our study demonstrated that after curative‐intent treatment, patients with NHL receiving more frequent surveillance CT scans would have an increased risk of SPM.