Twin studies on cancer

Background:Though the laryngeal cancer only has 1% of the total cancer cases and related deaths, it is a type of head and neck cancers with the highest prevalence. This study aims to investigate the epidemiological trend of laryngeal cancer with updated data on the global distribution of the disease burden.Materials and methods:The incidence and mortality rate of laryngeal cancer was extracted from GLOBOCAN (2020), Cancer Incidence in Five Continents series I-X, WHO mortality database, the Nordic Cancer Registries, and the Surveillance, Epidemiology, and End Results Program. The Global Health data exchanges for the prevalence of its associated risk factors. A Joinpoint regression analysis was used to calculate Average Annual Percentage Change (AAPC).Results:The age-standardised rate (ASR) of laryngeal cancer incidence and mortality were 2.0 and 1.0 per 100 000 worldwide. The Caribbean (ASR=4.0) and Central and Eastern Europe (ASR=3.6) had the highest incidence and mortality rate. Incidence and risk factors associated with laryngeal cancer included tobacco usage, alcohol consumption, poor diet, obesity, diabetes, hypertension, and lipid disorders. There was an overall decreasing trend in incidence, especially for males, but an increasing incidence was observed in female populations and younger subjects.Conclusions:As overall global trends of laryngeal cancer have been decreasing, especially for the male population, this could possibly be attributed to reduced tobacco use and alcohol consumption. Decrease in mortality may be due to improved diagnostic methods and accessibility to treatment, yet disparity in trend remains potentially because of differences in the level of access to surgical care. Disparities in temporal trends across countries may require further research and exploration to determine other underlying factors influencing this.

Correspondence to: You-Lin Qiao, Department of Cancer Epidemiology, Cancer Hospital/Institute, Chinese Academy of Medical Sciences, 17 South Panjiayuan Lane, Beijing 100021, PR China (nc.ca.smacic@yoaiq); and Philip R Taylor, Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 6120 Executive Blvd, Rm 7006, Rockville, Maryland, 20852-7236, USA (vog.hin.liam@rolyatp) Although substantial numbers of people worldwide take multivitamin supplements, including an estimated 40% or more of US adults, their effectiveness remains unclear. Recent reports from the Physicians’ Health Study (PHS) II, a randomized trial of daily multivitamins, found fewer total cancers in multivitamin recipients, but no effect on overall or cause-specific mortality 1, 2 in a Western population that was well nourished. However, few multivitamin trials have been conducted in under-nourished populations where the potential for benefit is most likely. In 1985, we initiated the Linxian Dysplasia Nutrition Intervention Trial (NIT) to evaluate the effect of multivitamin supplements on cancer incidence and mortality in Linxian, China, a region with extremely high rates of esophageal and gastric cardia cancer and multiple vitamin and mineral deficiencies. Individuals with a previous cytological diagnosis of esophageal squamous dysplasia were randomized to receive multivitamin supplementation or placebo for six years.3 Results after the six-year intervention period showed no statistically significant benefit on mortality.4 However, an additional 20 years of active follow-up after cessation of the intervention gave us the opportunity to examine the long-term effects of supplementation. The purpose of this report is to update results of the Linxian Dysplasia NIT after 26 years of follow-up to provide data informative on the effect of multivitamin supplementation on mortality in an under-nourished population. Our findings should be helpful for clinical practice and public health recommendations.

Background— The American Heart Association (AHA) has defined the concept of ideal cardiovascular health in promotion of the 2020 Strategic Impact Goals. We examined whether adherence to ideal levels of the 7 AHA cardiovascular health metrics was associated with incident cancers in the Atherosclerosis Risk In Communities (ARIC) study over 17 to 19 years of follow-up. Methods and Results— After exclusions for missing data and prevalent cancer, 13 253 ARIC participants were included for analysis. Baseline measurements were used to classify participants according to 7 AHA cardiovascular health metrics. Combined cancer incidence (excluding nonmelanoma skin cancers) from 1987 to 2006 was captured using cancer registries and hospital surveillance; 2880 incident cancer cases occurred over follow-up. Cox regression was used to calculate hazard ratios for incident cancer. There was a significant ( P trend <0.0001), graded, inverse association between the number of ideal cardiovascular health metrics at baseline and cancer incidence. Participants meeting goals for 6 to 7 ideal health metrics (2.7% of the population) had 51% lower risk of incident cancer than those meeting goals for 0 ideal health metrics. When smoking was removed from the sum of ideal health metrics, the association was attenuated with participants meeting goals for 5 to 6 health metrics having 25% lower cancer risk than those meeting goals for 0 ideal health metrics ( P trend =0.03). Conclusions— Adherence to the 7 ideal health metrics defined in the AHA 2020 goals is associated with lower cancer incidence. The AHA should continue to pursue partnerships with cancer advocacy groups to achieve reductions in chronic disease prevalence.

Although implants have been linked to malignancies in other medical contexts, such as the relationship between anaplastic large cell lymphoma and breast implants, the potential association between orthopaedic implants and cancer remains unclear. Several studies have investigated this question, but findings have been inconsistent. A comprehensive meta-analysis is needed to clarify whether total joint arthroplasty increases the risk of malignancy. (1) Is receiving a THA or TKA associated with an increased risk of cancer? (2) Are certain implant types (such as metal-on-metal or cemented) associated with increased cancer risk? (3) Is follow-up duration associated with changes in observed cancer risk estimates? A systematic review and meta-analysis were conducted using PubMed, Embase, and SCOPUS to identify studies assessing cancer incidence rates in patients who received hip or knee arthroplasty compared to patients in control groups who did not receive arthroplasty. Databases were queried from inception through the final search date (November 23, 2024). Eligible studies reported or allowed derivation of an effect estimate comparing overall cancer incidence rates in recipients of THA or TKA with an external reference population. From 1838 screened articles, 16 studies were included, all of which provided extractable effect estimates that were entered into one or more of our meta-analyses. Included studies consisted primarily of record-linkage studies connecting national, longitudinally maintained arthroplasty registers to similarly longitudinal national mortality and cancer registers. Study quality was assessed using the Newcastle-Ottawa Scale, which awards up to nine points across three categories, with higher scores indicating lower risk of bias. The 16 included studies scored between 6 and 8 (mean ± SD 7.1 ± 0.8), reflecting generally high methodological quality. The primary analysis included data from 977,465 patients of both sexes and all age groups who underwent hip or knee arthroplasty and were followed up for over 7,415,134 person-years. Effect estimates were pooled with a random-effects model because heterogeneity was present (between-study σ 2 = 0.016 versus within-study σ 2 = 0.002; Q = 1195, p < 0.001), and a funnel plot showed no evidence of publication bias. To explore associations between implant type and cancer risk for patients undergoing THA, we conducted separate meta-analyses for studies reporting on metal-on-metal bearing surfaces and those reporting on cemented fixation. To assess latency effects, we compared cancer incidence rates in patients with more or less than 10 years of follow-up and conducted a meta-regression to evaluate the association between follow-up duration and cancer risk. We did not perform an a priori power analysis. Patients who underwent THA or TKA did not have an increased risk of cancer compared with the general population (pooled random-effects estimate [REE] = 0.99 [95% confidence interval (CI) 0.92 to 1.07]; p = 0.88). Subgroup analyses showed no increased cancer risk after TKA (pooled REE = 1.02 [95% CI 0.85 to 1.21]; p = 0.83) or THA (pooled REE = 0.99 [95% CI 0.91 to 1.07]; p = 0.73). Cancer risk did not increase among patients undergoing THA who received cemented implants (pooled REE = 1.00 [95% CI 0.87 to 1.15]; p = 0.93) or metal-on-metal implants (pooled REE = 1.02 [95% CI 0.85 to 1.21]; p = 0.86) compared with the general population. Among patients with ≥ 10 years of follow-up, cancer incidence did not differ from the general population (pooled REE = 1.05 [95% CI 0.97 to 1.14]; p = 0.21); similarly, among patients with < 10 years of follow-up, no increased cancer risk was observed (pooled REE = 0.93 [95% CI 0.81 to 1.06]; p = 0.27). Meta-regression showed no association between follow-up duration and cancer risk (β = -0.004 [95% CI -0.024 to 0.015]; p = 0.66). Based on these findings, clinicians can continue to recommend arthroplasty without additional cancer-related concern based on current evidence. However, future studies should ensure longer follow-up, improved global representation in large linkage studies, and detailed patient- and implant-specific data to better characterize potential rare or long-latency malignancies. Level III, therapeutic study.

Introduction: Although survival from breast cancer is high (5-year survival: 88%), a subset of breast cancers are ultimately fatal. Pre-diagnosis lifestyle factors may influence which patients will die due to their disease. Examining the incidence of fatal breast cancer specifically is important for elucidating these factors, because most women with breast cancer do not die of the disease, and a specific effect on aggressiveness could be missed. Thus, in the Nurses’ Health Study cohorts (NHS and NHSII), we evaluated risk factors for fatal breast cancer. Methods: Any woman who died due to breast cancer at any time post-diagnosis was considered a fatal case. Hazards ratios (HRs) and 95% confidence intervals (CIs) for the association of reproductive and hormonal factors with incidence of fatal breast cancer were calculated using Cox proportional hazards regression. NHS and NHSII were combined using meta-analysis. Fatal and non-fatal cases were also compared for heterogeneity using competing risks analysis. For this analysis, we restricted to women who had had 15 years of post-diagnosis follow-up and defined a fatal case as any case for whom death due to breast cancer occurred within 15 years of diagnosis. Results: We documented 1,736 fatal cases of breast cancer over 30 years of follow-up in NHS and 275 cases over 20 years of follow-up in NHSII. Similar to incidence of total breast cancer, increasing parity, younger age at first birth, and older age at menarche, and younger age at menopause tended to be associated with decreased risk of fatal breast cancer (Table). Compared to non-fatal cases, increasing age, age at first birth, age at natural menopause and time since quitting smoking were more strongly associated with fatal breast cancer than with non-fatal breast cancer(p-heterogeneity&amp;lt;0.05). Table. Associations between reproductive and hormonal factors and risk of fatal breast cancer in the Exposure Total cases Fatal cases HR (95% CI) HR (95% CI) N = 12,262 N = 2,011 Parity Ever Parous 1.01 (0.94–1.09) 0.87 (0.72–1.04) Number of children among parous 0.95 (0.94–0.97) 0.97 (0.94–1.00) Age at first birth (among parous women) continuous, per 5 year increase 1.15 (1.12–1.19) 1.15 (1.07–1.22) Duration of breastfeeding (among parous women), per 1 year increase 0.98* (0.92–1.04) 1.03 (0.99–1.06) Age at menarche, continuous, per 1 year increase 0.97 (0.96–0.98) 0.97 (0.94–1.00) Age at natural menopause Pre/Unknown 1.03 (0.95–1.13) 0.85 (0.70–1.04) &amp;lt;45 0.77* (0.51–1.16) 0.71 (0.38–1.35) 45-&amp;lt;50 0.90 (0.84–0.97) 0.96 (0.58–1.60) 50-&amp;lt;53 1.00 (ref.) 1.00 (ref.) 53+ 1.03 (0.88–1.20) 1.05 (0.86–1.27) Oral contraceptive use Ever use 1.01 (0.96–1.05) 1.02 (0.92–1.13) Duration of use, per 5 year increase 1.03 (1.00–1.07) 1.07 (1.00–1.14) Tubal ligation 1.01 (0.96–1.06) 0.97 (0.81–1.16) Oophorectomy None 1.00 (ref.) 1.00 (ref.) 1 ovary removed 0.95 (0.88–1.04) 0.67 (0.52–0.87) both ovaries removed 0.86 (0.66–1.13) 0.95 (0.79–1.14) unknown number of ovaries removed 1.04 (0.76–1.41) 1.55 (0.89–2.72) Hysterectomy None 1.00 (ref.) 1.00 (ref.) Hysterectomy with no oophorectomy 0.96 (0.89–1.04) 0.86 (0.67–1.11) Hysterectomy with at least one ovary removed 0.80* (0.58–1.10) 0.80 (0.66–0.98) Smoking Never 1.00 (ref.) 1.00 (ref.) Former 1.07 (1.03–1.11) 0.97 (0.88–1.08) Current 1.02 (0.97–1.08) 1.02 (0.90–1.15) Time since quitting Current smoker 1.00 (ref.) 1.00 (ref.) &amp;lt;10 years 1.06 (0.98–1.14) 0.93 (0.78–1.11) 10–19 years 1.10 (0.94–1.29) 1.10 (0.81–1.50) 20+ years 0.97 (0.86–1.09) 0.90 (0.75–1.07) Never smoker 0.96 (0.92–1.02) 0.98 (0.87–1.10) Family history of breast cancer Any 1st degree family history 1.67 (1.50–1.85) 1.47 (1.28–1.68) Per number of relatives with breast cancer 1.62 (1.45–1.80) 1.47 (1.30–1.67) All models are adjusted for age, birth index, family history of breast cancer, history of benign breast disease, BMI, alcohol intake, age at menarche, physical activity, duration of OC use, menopause status, PMH use (by type), and age at menopause *p-heterogeneity between NHS and NHSII &amp;gt;0.05 Conclusion: Increasing age, age at first birth, and time since quitting smoking are more strongly associated with fatal breast cancer, suggesting that these factors may help predict which women are at risk of more aggressive breast cancers. Citation Format: Elizabeth M. Poole, A. Heather Eliassen, Susan E. Hankinson, Bernard A. Rosner, Walter C. Willett, Rulla M. Tamimi, Shelley S. Tworoger. Hormonal and reproductive risk factors for fatal breast cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 127. doi:10.1158/1538-7445.AM2013-127

Cancer in Australia: A Model for other Asia‐Pacific Countries

The Chinese National Twin Registry is the first and largest population-based twin registry in China. It was established in 2001. The primary goal of this program is the establishment of a population-based twin registry of 45,000 twin pairs from several regions representing north, south, urban, and rural areas in China. A secondary goal is to study genetic contributions to complex diseases, and to test associations of candidate genes with related phenotypes. Seven thousand, four hundred and twenty-three twin pairs have been enrolled in the registry, in which 1613 pairs have undergone detailed questionnaire assessments and physical examination. Based on the baseline registry, a twin cohort was established. Continued research includes studies on intermediate phenotypes of cardiovascular and cerebrovascular diseases and psychological studies in adult twins, studies on growth and development in adolescent twins, and so forth. The current state and future plans for the Chinese National Twin Registry will be discussed in this article.

Differences in Nordic cancer patient survival observed today originate from the 1970s, but were first identified in a mortality prediction from 1995. This paper provides timely comparisons of survival using NORDCAN, a database with comparable information from the Nordic cancer registries. Elucidation of the differences is important when monitoring cancer care generally and evaluating the impact of cancer plans. Material and methods. The NORDCAN database 1964–2003 with follow-up for death through 2006, was used to analyse incidence, mortality, and survival for all NORDCAN cancer sites. We analysed 5-year relative survival and excess mortality rates in the first three months and 2–5 years after diagnosis. Results. The time trends in survival 1989–2003 were largely similar between the Nordic countries with increases in 14 sites among men and 16 among women. In all countries the excess mortality rates were highest in the first three months after diagnosis, but decreased to similar levels across all countries 2–5 years after diagnosis. Comparing countries excess mortality was highest in Denmark irrespective of follow-up period. Lower survival was observed for Danish cancer patients in 23 of the 33 cancer sites in men and 26 of 35 sites in women. Low and similar levels of survival were observed for cancers of the oesophagus, lung, liver and pancreas, while an 8–10 percentage point difference in survival was found between countries for colorectal cancer. Conclusion. The notable differences in Nordic cancer patient survival can be linked to national variations in risk factors, co-morbidity, and the implementation of screening. Improved treatment and primary prevention, in particular the targeting of tobacco and alcohol use, is required to improve cancer control. The recently-initiated cancer plans in Denmark and Norway are yet to show an observable effect on the corresponding cancer survival.

Background: The incidence of cancer is on the rise in India as well as around the globe. Earlier oral, breast, and cervical cancers constituted a major burden of cancer in India. However, the recent world statistics suggest that the proportion of lung, colorectal, breast, and prostate cancers is increasing. The Indian National Cancer Registry reports provide robust data regarding the cancer incidence in India. Objectives: We aimed to analyze the Indian National Cancer Registry report of 2020 to determine whether there has been a change in the trend of cancer incidence. Materials and Methods: Six population-based cancer registries (PBCR) with the highest number of patients were selected from each zone of the country. From these, a total of 1,87,891 patients were included in the study to ensure a pan-India representation. The relative proportion of oral, breast, cervical, lung, ovarian, endometrial, and prostate cancers was determined from these PBCRs. The mean of these values for each of these cancer types from the six PBCRs was considered the mean proportion of these cancer types across the country. Results: According to data from the PBCRs, lung and oral cancers were found to be the leading cancer types among men, and breast and cervix uteri cancers among women. The mean relative proportions showed that oral, breast, and cervical cancers still constitute the major bulk of this disease in India. Moreover, it was observed that the incidence of lung cancer has significantly increased. Likewise, the incidence of the cancers of the prostate, ovary and endometrium is also on the rise. The highest age-adjusted incidence rates (AAR) for men were noted in the Aizawl district of Mizoram and the highest AAR for women was in Papumpare district of Arunachal Pradesh. Conclusion: There continues to be a disproportionately high incidence of cancers in northeast India. Policymakers and healthcare professionals should focus on the emerging cancers along with oral, breast, and cervical cancers, which still constitute the major cancer burden in our country.

Worldwide Distribution, Risk Factors, and Temporal Trends of Testicular Cancer Incidence and Mortality: A Global Analysis

Lip, oral and pharyngeal cancers make up a small percentage of total cancer cases worldwide and have reported lower rates of cancer-related deaths globally in 2020, but their 5-year survival rate in either early or advanced stages is different. The study evaluated the global incidence, mortality, risk factors, and temporal trends by age, gender, and geographical locations of lip, oral cavity, and pharyngeal cancer. Incidence and mortality rates were extracted from Cancer Incidence in Five Continents (CI5) volumes I-XI, the Nordic Cancer Registries (NORDCAN), the Surveillance, Epidemiology, and End Results (SEER) Program, and the WHO IARC mortality database. Joinpoint regression was used to calculate the Average Annual Percentage Change to examine trends. The highest incidence rates were found in Melanesia and South-Central Asia and mortality rates were 8.2 and 7.5. Risk factors associated with incidence and mortality included HDI, tobacco use, alcohol consumption, poor diet, and chronic health conditions such as hypertension. Increasing trends of incidence and mortality were observed in females from Malta; males aged 50 and above from the United Kingdom, and females aged 50 and above from Slovakia reporting the largest increase. Although global incidence and mortality trends reported an overall decrease, significant increases were found for older age groups and female subjects. Incidence increase may be due to the growing prevalence of lifestyle, metabolic risk factors, and HPV infections, especially in developed countries.

BackgroundResidents of geothermal areas have higher incidence of non-Hodgkin’s lymphoma, breast cancer, prostate cancer, and kidney cancers than others. These populations are exposed to chronic low-level ground gas emissions and various pollutants from geothermal water. The aim was to assess whether habitation in geothermal areas and utilisation of geothermal water is associated with risk of cancer according to duration of residence.MethodsThe cohort obtained from the census 1981 was followed to the end of 2013. Personal identifier was used in record linkage with nation-wide emigration, death, and cancer registries. The exposed population, defined by community codes, was located on young bedrock and had utilised geothermal water supply systems since 1972. Two reference populations were located by community codes on older bedrock or had not utilised geothermal water supply systems for as long a period as had the exposed population. Adjusted hazard ratio (HR), 95% confidence intervals (CI) non-stratified and stratified on cumulative years of residence were estimated in Cox-model.ResultsThe HR for all cancer was 1.21 (95% CI 1.12–1.30) as compared with the first reference area. The HR for pancreatic cancer was 1.93 (1.22–3.06), breast cancer, 1.48 (1.23–1.80), prostate cancer 1.47 (1.22–1.77), kidney cancer 1.46 (1.03–2.05), lymphoid and haematopoietic tissue 1.54 (1.21–1.97), non-Hodgkin´s lymphoma 2.08 (1.38–3.15) and basal cell carcinoma of the skin 1.62 (1.35–1.94). Positive dose-response relationship was observed between incidence of cancers and duration of residence, and between incidence of cancer and degree of geothermal/volcanic activity in the comparison areas.ConclusionsThe higher cancer incidence in geothermal areas than in reference areas is consistent with previous findings. As the dose-response relationships were positive between incidence of cancers and duration of residence, it is now more urgent than before to investigate the chemical and physical content of the geothermal water and of the ambient air of the areas to detect recognized or new carcinogens.

2 University of Oklahoma College of Medicine/ Troy and Dolly Smith Cancer Center, Integris Baptist Medical Center, Oklahoma City, Oklahoma. A Brief History of Cancer Data in American Indians and Alaska Natives The risk for cancer has increased for American Indian and Alaska Native (AI/AN) populations since the beginning of the 20th century. This population is smaller in size and is younger than other racial/ ethnic groups, having survived the extermination policy of the US government in the 19th century and the decimation of the indigenous population by disease brought by the Europeans. Cancer statistics have not been easily obtained, nor accurate, for this special population. Tribal recognition, self-identification, and sporadic data collection concerning AI/AN populations have been fragmented. Only recently have improved data been prioritized by state health departments and hospital and central cancer registries.

Introduction: A substantial proportion of patients with atrial fibrillation (AF) die of non-cardiovascular causes, and recent studies suggest a link between AF and cancer. However, this association has not been evaluated in long-term prospective studies. Methods: A total of 34691 women ≥45 years and free of AF, cardiovascular disease and cancer at baseline were prospectively followed for incident AF and malignant cancer within the Women’s Health Study. All incident AF and cancer events were validated by medical record review. Cox proportional-hazards models using time-updated covariates were constructed to assess the relationship of new-onset AF with incident cancer and to adjust for potential confounders. We then assessed the risk of incident AF among women with cancer using a similar modelling approach. Results: Mean age at baseline was 55±7 years. During 19.1 years of follow-up, we observed 1467 (4.2%) AF and 5130 (14.8%) cancer events. AF was a significant risk factor for incident cancer in age-adjusted (hazard ratio (HR) 1.58, 95% confidence interval (CI), 1.34, 1.87, p&lt;0.0001) and multivariable adjusted (HR 1.49, 95% CI, 1.26, 1.77, p&lt;0.0001) models, and was increased among women with paroxysmal (HR 1.35, 95% CI 1.09, 1.67, p=0.005) and non-paroxysmal AF (HR 1.61, 95% CI 1.23, 2.09, p=0.0004). The risk of cancer was highest in the first 3 months after new-onset AF (HR 3.53, 95% CI 2.05, 6.08, p&lt;0.0001) but remained significant beyond 1 year (adjusted HR 1.44, 95% CI 1.19, 1.73, p=0.0001). New-onset AF was also associated with an increased risk of cancer mortality (adjusted HR 1.37, 95% CI 1.01, 1.85, p=0.04). In contrast, women with new-onset cancer had an increased risk of incident AF within 3 months (HR 4.61, 95% CI 2.81, 7.54, p&lt;0.0001) but not beyond 1 year (HR 1.17, 95% CI 0.97, 1.41, p=0.11). Conclusions: In this large cohort of initially healthy women, new-onset AF was a significant risk factor for the short and long term diagnosis of incident cancer. In contrast, cancer was not associated with an increased AF risk over the long term. Our results may suggest that AF could be an early sign of occult cancer or an underlying systemic process conferring an increased cancer risk.

The objective of this study was to assess the reciprocal association between non-Hodgkin lymphoma (NHL) and Merkel cell carcinoma (MCC) using the data of four Nordic Cancer Registries. Data for this study were drawn from the Danish, Finnish, Norwegian, and Swedish cancer registries. Standardized incidence ratios (SIRs) for MCC among NHL patients, and for NHL among MCC patients, were calculated. There were 109 838 individuals with NHL and 1411 individuals with MCC, of which 28 had joint occurrence of NHL and MCC. In 18 cases, NHL was diagnosed first, and in 10 cases, MCC was diagnosed first. The SIR for MCC after NHL was 4.34 (95% confidence interval 2.57–6.85). The SIR for NHL after MCC was 3.13 (1.50–5.77). Although the absolute frequency of joint occurrence of MCC and NHL is low, individuals suffering from one of the cancer forms have an increased risk of the other.