Reproductive factors and breast cancer risk in Iceland. A second cohort study

In a previous prospective study we showed elevated risks for breast cancer in nulliparous women compared to parous women, in those having their first pregnancy at a higher age, and those with few children. This was based on 216 women diagnosed with breast cancer during 1965 to 1975 among 34,525 women having attended the cervix cancer detection clinic in Iceland by the end of 1974, and born between 1906 and 1945. The present investigation on 848 cases, diagnosed among 6 1,040 women attending the cervix cancer detection clinic during 1964 to 1984 and born between 1901 and 1960, shows the same risk factors to be significant. The relative risks are, however, smaller. The reasons for the difference in relative risks are discussed, We find that the effect of age at first birth is significant for women up to the age of 65 and not for older women. In both cohorts, women older than 55 are underrepresented and more so in the earlier report. In addition, the small number of cases in the reference group with age at first birth below 20 appears to have made the figures of our earlier report unreliable.     

Cancer risk following organ transplantation: a nationwide cohort study in Sweden

A substantial excess risk of lymphomas and nonmelanoma skin cancer has been demonstrated following organ transplantation. Large sample size and long follow-up time may, however, allow more accurate risk estimates and detailed understanding of long-term cancer risk. The objective of the study was to assess the risk of cancer following organ transplantation. A nationwide cohort study comprising 5931 patients who underwent transplantation of kidney, liver or other organs during 1970-1997 in Sweden was conducted. Complete follow-up was accomplished through linkage to nationwide databases. We used comparisons with the entire Swedish population to calculate standardised incidence ratios (SIRs), and Poisson regression for multivariate internal analyses of relative risks (RRs) with 95% confidence intervals (CI). Overall, we observed 692 incident first cancers vs 171 expected (SIR 4.0; 95% CI 3.7-4.4). We confirmed marked excesses of nonmelanoma skin cancer (SIR 56.2; 95% CI 49.8-63.2), lip cancer (SIR 53.3; 95% CI 38.0-72.5) and of non-Hodgkin's lymphoma (NHL) (SIR 6.0; 95% CI 4.4-8.0). Compared with patients who underwent kidney transplantation, those who received other organs were at substantially higher risk of NHL (RR 8.4; 95% CI 4.3-16). Besides, we found, significantly, about 20-fold excess risk of cancer of the vulva and vagina, 10-fold of anal cancer, and five-fold of oral cavity and kidney cancer, as well as two- to four-fold excesses of cancer in the oesophagus, stomach, large bowel, urinary bladder, lung and thyroid gland. In conclusion, organ transplantation entails a persistent, about four-fold increased overall cancer risk. The complex pattern of excess risk at many sites challenges current understanding of oncogenic infections that might become activated by immunologic alterations.     

Cancer risk in patients with Hashimoto's thyroiditis: a nationwide cohort study

Background:

This study examined the risk of cancer in patients with Hashimoto''s thyroiditis (HT).

Methods:

The Taiwanese National Health Insurance Research Database (NHIRD) was used to identify 1521 newly diagnosed HT patients from 1998–2010, and 6084 frequency-matched non-HT patients. The risk of developing cancer for HT patients was measured using the Cox proportional hazard model.

Results:

The incidence of developing cancer in the HT cohort was 5.07 per 1000 person-years, which was 1.68-fold higher than that in the comparison cohort (P<0.001). Compared with patients aged 20–34 years, patients in older age groups had a higher risk of developing cancer (35–55 years: hazard ratio (HR)=5.96; >55 years: HR=9.66). After adjusting for sex, age, and comorbidities, the HT cohort had HRs of 4.76 and 11.8 for developing colorectal cancer and thyroid cancer, respectively, compared with non-HT cohort. Furthermore, the HT cohort to non-HT cohort incidence rate ratio (IRR) of thyroid cancer was higher in the first 3 years (48.4, 95% confidence interval (CI)=35.0–66.3), with an adjusted HR of 49.4 (95% CI=6.39–382.4).

Conclusion:

Hashimoto''s thyroiditis patients have a higher risk of thyroid cancer and colorectal cancer. The thyroid cancer prevention effort should start soon after HT is diagnosed, while being cautious of colorectal cancer increases with time.     

Cancer risk in a cohort of polio patients

Poliomyelitis has hypothetically been associated with an increased risk of central nervous system (CNS) tumors. The present study was performed to examine not only the risk of CNS tumors but also the overall risk of cancer among a cohort of 5,883 polio patients. Patients diagnosed with acute poliomyelitis in the Danish capital, Copenhagen, between 1919 and 1954 were identified and followed with respect to cancer. Information on vital status and cancer diagnoses was obtained through linkage with the Danish Civil Registration System and the Danish Cancer Registry, respectively. The ratio of observed number of cancers to the number expected from population-based incidence rates, i.e., the standardized incidence ratio (SIR), served as measure of the relative cancer risk. Overall, 717 cases of cancer were observed among 5,883 polio patients during 249,084 person-years of follow-up vs. an expected number of 645 (SIR = 1.11 [95% confidence interval 1.03 to 1.20])). The increased risk was restricted to female polio patients (SIR = 1.18 [1.07 to 1.30]), among whom the risk was particularly high for breast cancer (SIR = 1.35 [1.12 to 1.61]) and for skin cancer (SIR = 1.66 [1.32 to 2.07]). The risk of breast cancer was highest among women with a history of paralytic polio (SIR = 1.62 [1.24 to 2.10]). The observed number of CNS tumors did not exceed the expected (SIR = 1.09 [0.72 to 1.60]). Women diagnosed with poliomyelitis, in particular paralytic polio, may be at increased risk of breast cancer. There was no association between malignancies of the CNS and poliomyelitis.     

Cancer risk following polymyositis and dermatomyositis: a nationwide cohort study in Denmark

Polymyositis and dermatomyositis (PM/DM) have been associated with cancer, although the long-term risks are poorly understood. To evaluate the risk of cancer by time periods subsequent to PM/DM diagnosis, a cohort of 539 patients hospitalized with PM/DM in Denmark between 1977 and 1989 was identified from the Danish Central Hospital Discharge Register. Cancer incidence among cohort members was ascertained by linkage to the Danish Cancer Registry using a unique personal-identification number. The overall cancer risk was elevated significantly among patients with DM (standardized incidence ratio [SIR]=3.8, 95 percent confidence interval [CI]=2.6–5.4) and to a lesser extent PM (SIR=1.7, CI=1.1–2.4). Significant excesses were observed for cancers of lung, ovary, and lymphatic and hematopoietic system. However, the excess cancer incidence declined steadily with increasing years since initial diagnosis of PM/DM. The cancer risk was increased about sixfold (SIR=5.9, CI=3.8–8.7) during the first year, but was lower during the second year (SIR=2.5, CI=1.1–4.8), with no significant excesses in subsequent years of follow-up. These findings confirm that PM/DM may occur as a paraneoplastic syndrome that calls for steps aimed at early cancer detection and treatment. Among long-term survivors of PM/DM, however, there is little evidence to warrant extensive preventive and screening measures beyond those recommended for the general population.Drs Chow, McLaughlin, and Fraumeni, and Ms Gridley are with the Epidemiology and Biostatistics Program, Division of Cancer Etiology, National Cancer Institute, Bethesda, MD, USA. Dr McLaughlin is currently with the International Epidemiology Institute, Rockville, MD. Ms Mellemkjær and Dr Olsen are with the Division for Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark. Address correspondence to Dr Chow, National Cancer Institute 6130 Executive Blvd, EPN/415, Rockville, MD 20852, USA.     

Cancer risk in patients with constitutional chromosome deletions: a nationwide British cohort study

The finding of increased risks of specific cancers in individuals with constitutional deletions of chromosomes 11p and 13q led to the discovery of cancer predisposition genes at these locations, but there have been no systematic studies of cancer risks in patients with constitutional deletions, across the chromosome complement. Therefore, we assessed cancer incidence in comparison with national cancer incidence rates in a follow-up of 2561 patients with constitutional autosomal chromosome deletions diagnosed by microscopy or fluorescence in situ hybridisation in Britain during the period 1965-2002. Thirty cancers other than non-melanoma skin cancer occurred in the cohort (standardised incidence ratio (SIR)=2.4, 95% confidence interval (CI) 1.6-3.5). There were significantly increased risks of renal cancer in persons with 11p deletions (SIR=1869, 95% CI 751-3850; P=4 x 10(-21)), eye cancer with 13q deletions (SIR=1084, 95% CI 295-2775; P=2 x 10(-11)), and anogenital cancer with 11q deletions (SIR=305, 95% CI 63-890; P=3 x 10(-7)); all the three latter cancers were in the 11 subjects with 11q24 deletions. The results strongly suggest that in addition to suppressor genes relating to Wilms' tumour risk on 11p and retinoblastoma on 13q, there are suppressor genes around 11q24 that greatly affect anogenital cancer risk.     

Cancer risk following primary hemochromatosis: A population-based cohort study in Denmark

A population-based cohort of 120 Danish men, discharged with a hospital diagnosis of primary hemochromatosis from 1977 to 1989, was followed up to 1989 for subsequent cancer risk. Nineteen subjects (including 6 with primary liver cancers) were excluded from the analysis, either because they died within the same month of hemochromatosis diagnosis or because they had cancer prior to diagnosis of hemochromatosis. Among the 101 remaining subjects, 4 primary liver cancers occurred one year or more after the diagnosis of hemochromatosis, far surpassing the expected number based on incidence rates from the Danish population (standardized incidence ratio 92.9, 95% confidence interval 25.0 to 237.9). The excess of liver cancer was associated with cirrhosis and included cholangiocarcinoma as well as hepatocellular carcinoma. Significantly elevated risks were also observed for non-hepatic cancers (13 cases; SIR 3.5, 95% CI 1.9 to 6.0), notably esophageal cancer (2 cases; SIR 42.9, 95% CI 4.8 to 154.9) and skin melanoma (2 cases; SIR 27.8, 95% CI 3.1 to 100.3). The results of this population-based study are in accordance with the hypothesis that patients with primary hemochromatosis have a substantial risk of primary liver cancer. Further studies of hemochromatosis may be useful in clarifying the relation of non-hepatic malignancies to body iron stores in the general population. © 1995 Wiley-Liss, Inc.     

Cancer incidence among marine engineers,a population-based study (Iceland)

Objectives: Marine engineers are in their occupation exposed to different chemicals, organic solvents, exhaust gases, oils, and petroleum products, and were formerly exposed to asbestos. The aim was to study the cancer pattern, with particular attention to lung and bladder cancer, in an Icelandic cohort of marine engineers, indirectly controlling for their smoking habits. Methods: A cohort of 6603 male marine engineers was followed up from 1955 to 1998, a total of 167,715 person-years. The cohort was record linked by the engineers' personal identification numbers to population-based registers containing the vital and emigration status and cancer diagnosis. Standardized incidence ratios (SIRs) were calculated for all cancers and different cancer sites in relation to different lag time and year of graduation. Information on smoking habits was obtained by administering a questionnaire to a sample of the cohort (n = 1501). Results: In the total cohort 810 cancers were observed, whereas 794 were expected (SIR 1.0, 95% CI 1.0–1.1), and significantly increased risk of stomach cancer (SIR 1.3, 95% CI 1.0–1.5) and lung cancer (SIR 1.2, 95% CI 1.0–1.5) was found. Increased risk of all cancers (SIR 1.2, 95% CI 1.1–1.3), stomach cancer (SIR 1.5, 95% CI 1.1–1.9), lung cancer (SIR 1.4, 95% CI 1.2–1.8), pleural mesothelioma (SIR 4.8, 95% CI 1.3–12.3), and urinary bladder cancer (SIR 1.3, 95% CI 1.0–1.8) were observed when a 40-year lag time was applied. The engineers' smoking habits were similar to those in a sample of the general population. The predictive value for lung cancer was 1.03. Conclusions: The increased risk for mesothelioma is possibly attributable to the previous asbestos exposure. The excess of lung cancer could also be related to asbestos exposure. The high incidence of stomach cancer, lung cancer, and bladder cancer may be related to exposure to chemical risk factors, such as oils and petroleum products, as confounding due to smoking seems to be ruled out. In the light of the limited exposure information in the present study the importance of the different occupational exposures needs to be evaluated in further studies.     

Cancer risk of Lichen planus: A cohort study of 13,100 women in Finland

The association between Lichen planus (LP) and cancer has been under debate for decades. We studied the connection via population‐based Finnish register data. All women with the diagnosis of LP (n = 13,100) were identified from the Finnish Hospital Discharge Registry from 1969–2012. These patients were linked with subsequent cancer diagnoses from the Finnish Cancer Registry until 2014. Standardized incidence ratios (SIRs) were counted for different cancers by dividing the observed numbers of cancers by expected numbers, which were based on national cancer incidence rates. In total, 1,520 women with LP were diagnosed with cancer (SIR 1.15, 95% confidence interval [CI] 1.09–1.20). LP was associated with an increased risk of cancer of lip (SIR 5.17, 95% CI 3.06–8.16), cancer of tongue (SIR 12.4, 95% CI 9.45–16.0), cancer of oral cavity (SIR 7.97, 95% CI 6.79–9.24), cancer of esophagus (SIR 1.95, 95% CI 1.17–3.04), cancer of larynx (SIR of 3.47, 95% CI 1.13–8.10) and cancer of vulva (SIR 1.99, 95% CI 1.18–3.13). The risk of cancer was not increased in other locations where LP manifests (pharynx and skin). Patients with diagnosed LP have an increased risk of developing cancer of lip, tongue, oral cavity, esophagus, larynx and vulva. These data are important when considering treatment and follow‐up of patients with LP diagnosis.     

Cancer risk in a cohort of subjects carrying a single mismatch repair gene mutation

Hereditary non-polyposis colon cancer (HNPCC) is an autosomal dominant condition, caused by germline mutations in the mismatch repair genes, that presents with colorectal cancers at a young age, as well as extracolonic tumours. One of the causative mutations is the C1528T (Exon 13) mutation of the MLH1 gene. The purpose of this study is to document the cancer risk for subjects who carry this mutation. This is a prospective cohort study of 200 subjects who carry this mutation. We calculated the risk of developing colorectal cancer only in those subjects who had not undergone surveillance colonoscopy. The incidence of extracolonic cancers (for which surveillance is not routinely offered) was determined for the entire cohort. The results of the study are among the 71 subjects who did not undergo surveillance colonoscopy, colorectal cancers occurred in 36 (51%). They occurred at a median age of 44 years (range 17–73). Using Kaplan–Meier estimates, the risk of developing a colorectal cancer by age 65 was 92%. Eighteen subjects in the cohort of 200 were diagnosed with extracolonic tumours. The most common extracolonic malignancies were breast (6/98 women) and endometrial (3/98 women). Thus this mutation has a high penetrance for colorectal cancer, but is not associated with a high risk of developing extracolonic malignancies.     

Cancer incidence in Holocaust male survivors—An Israeli cohort study

Previous studies, often using proxy exposure assessment and not controlling for individual risk factors, suggested higher cancer risk in Holocaust survivors. We have used individual‐level data from a male cohort of Israeli civil servants recruited in 1963 to investigate cancer incidence in Holocaust survivors, controlling for potential confounders. The analysis included 4,669 Europe‐born subjects; 689 exposed = E (immigrated to Israel after 1939 and reported of being in Nazi camps during World War II); 2,307 potentially exposed = PE (immigrated to Israel after 1939 and reported of not being in Nazi camps); and 1,673 non‐exposed = NE (immigrated to Israel prior to 1939). Vital status and cancer incidence in the cohort were determined based on national registries. Socioeconomic level, health behaviors and cancer incidence were compared between the groups and Cox proportional hazards regression models adjusting for potential confounders assessed hazard risk ratios for cancer by exposure status. All‐cause mortality was studied as a competing risk. In total, 241, 682, and 522 cancer cases were diagnosed in the E, PE, and NE, respectively. Compared with the NE, all‐site cancer incidence was higher in the E (HR = 1.13, 95%CI 0.97–1.32) but not in the PE. All‐cause mortality competed with all‐site invasive cancer incidence in the E group (HR = 1.18, 95%CI 1.02–1.38). Colorectal and lung cancer seemed to be positively though non‐significantly associated with the exposure while prostate cancer was not. Male Holocaust survivors may be at a weakly increased risk for all‐site, colorectal and lung cancer. The role of age at exposure and residual confounding should be further investigated.     

Cancer risk in patients with allergic rhinitis, asthma and atopic dermatitis: a nationwide cohort study in Taiwan

It has long been a debate that whether atopy is a risk factor or protective factor for cancer. However, no large-scale study of different cancers in patients with atopic diseases has been conducted among Asians. Here, we conducted a nationwide study to evaluate the cancer risk in patients with allergic rhinitis (AR), asthma and atopic dermatitis (AD). Drawing on Taiwan's National Health Insurance Research Database, 225,315 patients with AR, 107,601 patients with asthma and 34,263 patients with AD without prior cancers were identified in the period from 1996 to 2008. The standard incidence ratio (SIR) of each cancer was calculated. Although the overall cancer risks in patients with atopic symptoms were not increased, the risks were slightly elevated in female patients with AR or asthma (SIR: 1.13 and 1.08, AR and asthma, respectively) and slightly decreased in males patients with AR. Those aged 20-39 years-old possessed the highest risk. A higher risk of developing brain cancer was found in patients with atopic diseases, and patient with AR or asthma also had an elevated risk of developing cancer of kidney and urinary bladder. In contrast, the risk of nonmelanoma skin cancer was lower in patients with AR and asthma. Compared to patients with only one atopic disease, those with more than one atopic disease had lower cancer risks. Our data suggests that the association between atopy and cancer is site-specific.     

Cancer in Greenlandic Inuit 1973-1997: a cohort study

The increasing westernization of the Arctic countries may influence the very particular cancer profile of these populations. Our objective was to investigate the development in cancer incidence from 1973 to 1997 in a large and well-defined Inuit population in Greenland. Greenland is part of the Danish Kingdom, and population statistics covering both countries are available from the same registry resource. Data from the Danish Civil Registration System and from the Danish Cancer Registry were used to calculate age-standardized cancer incidence rates for the periods 1973-1987 and 1988-1997 for persons born in Greenland. Using rates for Denmark, sex-specific standardized incidence ratios (SIRs) for 1988-1997 were calculated. Furthermore, age- and sex-specific incidence rates in the 2 periods were calculated for selected cancers. Total cancer incidence increased from 248.5 to 277.9 per 100,000 person-years in men and from 269.4 to 302.2 per 100,000 person-years in women. The incidence of lung, stomach, breast and colon cancer increased, whereas the incidence of cervical cancer decreased. Compared to the Caucasian population in Denmark, high SIRs were found for cancers of the nasopharynx, salivary gland, esophagus, stomach and cervix and low SIRs for testis, bladder, prostate, breast and hematologic cancers. Overall cancer incidence among Greenlandic Inuit is increasing as a result of increases in several cancers that are common in Western populations. A significant increase in the incidence of stomach cancer in both sexes, which contrasts global trends for this cancer, warrants further investigation.     

Alcoholism and cancer risk: a population-based cohort study

The incidence of cancer was studied in a population-based cohort of 9,353 individuals (8,340 men and 1,013 women) with a discharge diagnosis of alcoholism in 1965–83, followed up for 19 years (mean 7.7). After exclusion of cancers in the first year of follow-up, 491 cancers were observed cf 343.2 expected through 1984 (standardized incidence ratio [SIR] = 1.4,95 percent confidence interval [CI] = 1.3–1.6). A similar excess risk of cancer was seen among men (SIR = 1.4, CI = 1.3–1.6) and among women (SIR = 1.5, CI = 1.1–2.0). We observed the established associations with cancers of the oral cavity and pharynx (SIR = 4.1, CI = 2.9–5.7), esophagus (SIR = 6.8, CI = 4.5–9.9), larynx (SIR = 3.3, CI = 1.7–6.0), and lung (SIR = 2.1, CI = 1.7–2.6), although confounding by smoking likely increased these risk estimates. While there was evidence of increased risk for pancreatic cancer (SIR = 1.5, CI = 0.9–2.3), alcoholism did not elevate the incidence of cancer of the stomach (SIR = 0.9, CI = 6–1.4), large bowel (SIR = 1.1, CI = 0.8–1.5), prostate (SIR = 1.0, CI = 0.8–1.3), urinary bladder (SIR = 1.0, CI = 0.6–1.5), or of malignant melanoma (SIR = 0.9, CI = 0.3–1.9). Among women, the number of breast cancers observed was close to expected (SIR = 1.2, CI = 0.6–2.2), although a significant excess number of cervical cancers occurred (SIR = 4.2, CI = 1.5–9.1). The results of this study, one of the first to evaluate the incidence of cancer in a population-based cohort of alcoholics of both sexes, are consistent with smaller previous studies, which were usually limited to cancer mortality and of short follow-up.Dr Adami is with the Cancer Epidemiology Unit, University Hospital, Uppsala, Sweden. Drs McLaughlin and Hsing are with the Biostatistics Branch, National Cancer Institute, Bethesda, MD, USA. Dr Wolk is with the Cancer Epidemiology Unit, University Hospital, Uppsala, Sweden. Dr Ekbom is with the Department of Surgery and with the Cancer Epidemiology Unit, University Hospital, Uppsala, Sweden. Dr Persson is with the Department of Obstetrics and Gynaecology and with the Cancer Epidemiology Unit, University Hospital, Uppsala, Sweden. Address correspondence to Dr Adami, Cancer Epidemiology Unit, University Hospital, S-751 85 Uppsala, Sweden. The work was performed at the Cancer Epidemiology Unit, Uppsala University, Sweden; the research was supported by grants from the Swedish Cancer Society.     

Dietary patterns and subsequent colorectal cancer risk by subsite: a prospective cohort study

In order to investigate the associations between dietary patterns and the risk of colorectal cancer by subsite in Japan, the baseline data from a population-based cohort study of 20,300 men and 21,812 women were analyzed. We conducted factor analysis and identified 3 major dietary patterns, "healthy," "traditional" and "Western," and calculated the factor scores of each pattern for individuals. During 10 years of follow-up, 370 colorectal cancer cases were identified. We found a positive association between the traditional pattern and colon cancer risk in women [rate ratio for highest quartile (RR) = 2.06; 95% CI = 1.10-3.84; p for trend = 0.11], but not in men. This positive association was slightly stronger for proximal colon cancer (RR = 2.07; 95% CI = 0.84-5.12) than for distal colon cancer (RR = 1.84; 95% CI = 0.75-4.50). After multivariate adjustment, the Western dietary pattern was also positively associated with colon cancer risk in females (RR = 2.21; 95% CI = 1.10-4.45), with the strongest associations being observed for females with distal colon cancer (RR = 3.48; 95% CI = 1.25-9.65). We did not observe any significant association between the healthy dietary pattern and colon cancer risk. For rectal cancer, no significant associations were found for the 3 dietary patterns. In conclusion, we found that the traditional and the Western dietary patterns were positively associated with colon cancer risk in females.