The purpose of this study was to assess the role of treatment in long-term overall and cardiovascular mortality after childhood cancer.
We studied 4,122 5-year survivors of a childhood cancer ...diagnosed before 1986 in France and the United Kingdom. Information on chemotherapy was collected, and the radiation dose delivered to the heart was estimated for 2,870 patients who had received radiotherapy.
After 86,453 person-years of follow-up (average, 27 years), 603 deaths had occurred. The overall standardized mortality ratio (SMR) was 8.3-fold higher (95% CI, 7.6-fold to 9.0-fold higher) in relation to the general populations in France and the United Kingdom. Thirty-two patients had died as a result of cardiovascular diseases (ie, 5.0-fold 95% CI, 3.3-fold to 6.7-fold more than expected). The risk of dying as a result of cardiac diseases (n = 21) was significantly higher in individuals who had received a cumulative anthracycline dose greater than 360 mg/m(2) (relative risk RR, 4.4; 95% CI, 1.3 to 15.3) and in individuals who received an average radiation dose that exceeded 5 Gy (RR, 12.5 and 25.1 for 5 to 14.9 Gy and > 15 Gy, respectively) to the heart. A linear relationship was found between the average dose of radiation to the heart and the risk of cardiac mortality (estimated excess corrected RR at 1 Gy, 60%).
This study is the first, to our knowledge, to establish a relationship between the radiation dose received by the heart during radiotherapy for a childhood cancer and long-term cardiac mortality. This study also confirms a significant excess risk of cardiac mortality associated with a high cumulative dose of anthracyclines.
French Polynesia has one of the highest incidence rates of thyroid cancer worldwide. Relationships with the atmospheric nuclear weapons tests and other environmental, biological, or behavioral ...factors have already been reported, but genetic susceptibility has yet to be investigated. We assessed the contribution of polymorphisms at the 9q22.33 and 14q13.3 loci identified by GWAS, and within the DNA repair gene ATM, to the risk of differentiated thyroid cancer (DTC) in 177 cases and 275 matched controls from the native population.
For the GWAS SNP rs965513 near FOXE1, an association was found between genotypes G/A and A/A, and risk of DTC. A multiplicative effect of allele A was even noted. An excess risk was also observed in individuals carrying two long alleles of the poly-alanine tract expansion in FOXE1, while no association was observed with rs1867277 falling in the promoter region of the gene. In contrast, the GWAS SNP rs944289 (NKX2-1) did not show any significant association. Although the missense substitution D1853N (rs1801516) in ATM was rare in the population, carriers of the minor allele (A) also showed an excess risk. The relationships between these five polymorphisms and the risk of DTC were not contingent on the body surface area, body mass index, ethnicity or dietary iodine intake. However, an interaction was evidenced between the thyroid radiation dose and rs944289.
A clear link could not be established between the high incidence in French Polynesia and the studied polymorphisms, involved in susceptibility to DTC in other populations. Important variation in allele frequencies was observed in the Polynesian population as compared to the European populations. For FOXE1 rs965513, the direction of association and the effect size was similar to that observed in other populations, whereas for ATM rs1801516, the minor allele was associated to an increased risk in the Polynesian population and with a decreased risk in the European population.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Thyroid doses were estimated for the subjects of a population-based case-control study of thyroid cancer in a population exposed to fallout after atmospheric nuclear weapons tests conducted in French ...Polynesia between 1966 and 1974. Thyroid doses due to (1) intake of I and of short-lived radioiodine isotopes (I, I, I) and Te, (2) external irradiation from gamma-emitting radionuclides deposited on the ground, and (3) ingestion of long-lived Cs with foodstuffs were reconstructed for each study subject. The dosimetry model that had been used in 2008 in Phase I of the study was substantially improved with (1) results of radiation monitoring of the environment and foodstuffs, which became available in 2013 for public access, and (2) historical data on population lifestyle related to the period of the tests, which were collected in 2016-2017 using focus-group discussions and key informant interviews. The mean thyroid dose among the study subjects was found to be around 5 mGy while the highest dose was estimated to be around 36 mGy. Doses from I intake ranged up to 27 mGy, while those from intake of short-lived iodine isotopes (I, I, I) and Te ranged up to 14 mGy. Thyroid doses from external exposure ranged up to 6 mGy, and those from internal exposure due to Cs ingestion did not exceed 1 mGy. Intake of I was found to be the main pathway for thyroid exposure accounting for 72% of the total dose. Results of this study are being used to evaluate the risk of thyroid cancer among the subjects of the epidemiologic study of thyroid cancer among French Polynesians.
Objectives French Polynesia has one of the world's highest thyroid cancer incidence rates. A case-control study among native residents of French Polynesia included 219 cases of differentiated thyroid ...cancers diagnosed between 1979 and 2004 (195 women/24 men) matched with 359 population controls (315 women/44 men) on the date of birth. Methods Anthropometric factors were analyzed by conditional logistic regression. Results The risk of thyroid cancer for women in the highest quartile of body mass index (BMI) before diagnosis and at age 18 was 2.3-fold higher (95% CI, 1.1-4.7 p = 0.04) and 2.3-fold higher (95% CI, 1.2-4.4 p < 0.01), respectively, compared with the lowest. Women who were overweight (BMI = 25-29.9 kg/m²) or obese (BMI >= 30 kg/m²) at age 18 and before diagnosis had an increased risk compared with those with a normal lifelong weight (OR = 6.2; 95% CI, 2.5-15.5 p < 0.01). Results for excess weight appeared in similar directions for men, although the number of cases was too small to provide reliable estimates. Height was positively associated with thyroid cancer among men and women. Conclusion This study shows the role of excess body weight, especially if the onset is during early adulthood, and elevated height in the risk of differentiated thyroid cancer in populations born in French Polynesia.
New Caledonia and French Polynesia have among of the world highest thyroid cancer incidence rates. Studies have demonstrated a relationship between anthropometric parameters and the prevalence of ...cancer. In this study we evaluated further the relationship between body mass index (BMI) and other anthropometric parameters on the incidence of thyroid cancer in the New Caledonia and French Polynesia populations.
We performed a pooled analysis of two case-control studies in New Caledonia and French Polynesia. We included a total of 554 cases (65 men and 489 women) of differentiated thyroid cancers and 776 population control subjects matched on sex, age, and study. Anthropometric factors (height, weight, BMI, body fat percentage BF%, and body surface area BSA), at age 18 and before diagnosis, were analyzed by conditional logistic regression, adjusting for other independent risk factors.
A high proportion of cases (73%) were overweight (25-29.9 kg/m(2)) or obese (≥30 kg/m(2)) before diagnosis of thyroid cancer (against 57% of control subjects). An increased risk of thyroid cancer was observed with greater height, weight, BMI, BF%, and BSA. The association of thyroid cancer risk with height, weight, BMI, and BF% did not remain when adjustment was made for BSA. By comparison, the odds ratios for the highest versus the lowest quartile of BSA at age 18 were 3.97 (95% confidence interval, 2.57-6.15; p < 0.001) for women and 4.06 (95% confidence interval, 1.03-16.06; p = 0.04) for men. The association between thyroid cancer risk and each of anthropometric factors did not depend on tumor size or menopausal status before diagnosis.
Among anthropometric factors, BSA plays a dominant role in thyroid cancer risk and explains the apparent role of BMI.
French Polynesia has one of the world's highest thyroid cancer incidence rates. Iodine is suspected to play a role in this high incidence. The objective of this study was to assess whether low ...dietary iodine is related to a higher risk of thyroid cancer in the French Polynesian population.
A case-control study was performed among native residents of French Polynesia. It included 229 cases of differentiated thyroid cancer diagnosed between 1979 and 2004 (203 women, 26 men) matched with 371 population controls (324 women, 47 men) on the date of birth. The current study is focused on dietary iodine intake and fish consumption (food rich in iodine) and analyzed by conditional logistic regression.
Daily dietary iodine intake was insufficient (<150 μg/day) in 60% of both cases and controls. A decreased risk of thyroid cancer was observed with a higher consumption of fish (p(trend)=0.008) and shellfish (p(trend)=0.002), and also with a higher dietary iodine intake (p(trend)=0.03). There was no significant interaction between the effects of the thyroid radiation dose and the dietary iodine intake (p=0.2).
French Polynesia is a mild iodine deficiency area in which a higher consumption of food from the sea and a higher dietary iodine intake are significantly associated with a decreased risk of thyroid cancer. The quantification of this reduction requires specific investigation of iodine intake in traditional Polynesian food.
Due to the amount of iodine 131 released in nuclear tests and its active uptake by the thyroid, differentiated thyroid carcinoma (DTC) is the most serious health risk for the population living near ...sites of nuclear tests. Whether low doses to the thyroid from nuclear fallout are associated with increased risk of thyroid cancer remains a controversial issue in medicine and public health, and a misunderstanding of this issue may be associated with overdiagnosis of DTCs.
This case-control study was conducted by extending a case-control study published in 2010 that included DTCs diagnosed between 1984 and 2003 by adding DTCs diagnosed between 2004 and 2016 and improving the dose assessment methodology. Data on 41 atmospheric nuclear tests conducted by France between 1966 and 1974 in French Polynesia (FP) were assessed from original internal radiation-protection reports, which the French military declassified in 2013 and which included measurements in soil, air, water, milk, and food in all FP archipelagos. These original reports led to an upward reassessment of the nuclear fallout from the tests and a doubling of estimates of the mean thyroid radiation dose received by inhabitants from 2 mGy to nearly 5 mGy. Included patients were diagnosed from 1984 to 2016 with DTC at age 55 years or younger and were born in and resided in FP at diagnosis; 395 of 457 eligible cases were included, and up to 2 controls per case nearest by birthdate and matched on sex were identified from the FP birth registry. Data were analyzed from March 2019 through October 2021.
The radiation dose to the thyroid gland was estimated using recently declassified original radiation-protection service reports, meteorological reports, self-reported lifestyle information, and group interviews of key informants and female individuals who had children at the time of these tests.
The lifetime risk of DTC based on Biological Effects of Ionizing Radiation (BEIR) VII models was estimated.
A total of 395 DTC cases (336 females 85.1%; mean SD age at end of follow-up, 43.6 12.9 years) and 555 controls (473 females 85.2%; mean SD age at end of follow-up, 42.3 12.5 years) were included. No association was found between thyroid radiation dose received before age 15 years and risk of DTC (excess relative risk ERR per milligray, 0.04; 95% CI, -0.09 to 0.17; P = .27). When excluding unifocal noninvasive microcarcinomas, the dose response was significant (ERR per milligray, 0.09; 95% CI, -0.03 to 0.02; P = .02), but several incoherencies with the results of the initial study reduce the credibility of this result. The lifetime risk for the entire FP population was 29 cases of DTC (95% CI, 8-97 cases), or 2.3% (95% CI, 0.6%-7.7%) of 1524 sporadic DTC cases in this population.
This case-control study found that French nuclear tests were associated with an increase in lifetime risk of PTC in FP residents of 29 cases of PTC. This finding suggests that the number of thyroid cancer cases and the true order of magnitude of health outcomes associated with these nuclear tests were small, which may reassure populations of this Pacific territory.
French Polynesia has one of the world's highest thyroid cancer incidence rates. A case-control study among native residents of French Polynesia included 229 cases of differentiated thyroid cancer ...diagnosed between 1979 and 2004, and 371 population controls. Dietary patterns and goitrogenic food consumption (cabbage, cassava) were analyzed. We used a factor analysis to identify dietary patterns and a conditional logistic regression analysis to investigate the association between dietary patterns or food items and thyroid cancer risk. Two distinct dietary patterns were identified: traditional Polynesian and Western. A nonsignificant inverse association was observed between the traditional Polynesian dietary pattern and thyroid cancer risk. The Western pattern was not associated with thyroid cancer risk. Cassava consumption was significantly associated with a decreased risk of thyroid cancer. In conclusion, a traditional Polynesian dietary pattern led to a weak reduced risk of thyroid cancer in French Polynesia. The protective effect of cassava on this cancer does not seem to be substantially different from that of cabbage, which was the main goitrogenic food studied to date.
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DOBA, IJS, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK, VSZLJ
French Polynesia has one of the world's highest incidence rates of thyroid cancer. A case-control study among native residents of French Polynesia included 201 women diagnosed with differentiated ...thyroid cancer before the age of 56 years, between 1981 and 2004, matched to 324 population controls on date of birth. Face-to-face interviews were conducted from 2002 to 2004. Odds ratios were calculated by using conditional logistic regression and were reported in the total group and by ethnic group (“Polynesian” vs. “mixed”). The risk of thyroid cancer increased with natural (odds ratio = 1.9) or artificial (odds ratio = 4.5) menopause compared with that associated with a premenopausal status and with number of births (p for trend = 0.03): odds ratios for one, two, three, four or five, six or seven, and eight or more births were, respectively, 0.90, 1.6, 2.3, 2.2, 2.7, and 1.7 compared with a nulliparous status. Similar results were observed for Polynesian women. No association was observed with irregular menstrual cycles, age at menopause, history of miscarriage or induced abortion, time since last birth, age at and outcome of first pregnancy, or breastfeeding. This study confirms the role of menstrual and reproductive factors in the risk of differentiated thyroid cancer in Pacific island populations.
Differentiated thyroid carcinoma is considered to be the nonhereditary cancer for which familial inheritance is the highest. To date, no familial aggregation analysis of this cancer has been ...performed in Maohi populations, which exhibit a very high incidence rate. Therefore, we evaluate the risk of differentiated thyroid cancer associated with a family history of thyroid cancer in natives of French Polynesia.
We investigated thyroid cancer incidence in the first-degree relatives of 225 cases of differentiated thyroid carcinomas diagnosed between 1979 and 2004 in patients born in French Polynesia, and 368 randomly selected population controls matched for sex and age, born and residing in French Polynesia. All but five thyroid cancers declared among relatives were validated.
Twenty-four cases declared a family history of thyroid cancer, when compared with 11 controls. Individuals with an affected first-degree relative had a 4.5-fold (95% confidence interval CI, 1.9-10.6) increased risk of differentiated thyroid cancer. This odds ratio (OR) was not significantly higher when a male first-degree relative was affected (OR, 10.0; 95% CI, 1.3-74.8) compared with a female (OR, 4.0; 95% CI, 1.5-10.3) and was not different for patients who had a nonaggressive thyroid microcarcinoma (OR, 3.5; 95% CI, 0.6-16.4) than those who had a larger cancer (OR, 6.0; 95% CI, 1.8-20.5). This OR was borderline significantly (p, 0.07) higher in Maohis (OR, 11.0; 95% CI, 2.4-48.8) than in individuals of mixed origin (OR, 2.1; 95% CI, 0.8-5.9).
Our study shows that the familial inheritance of differentiated thyroid cancer is particularly high in Maohi populations.
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