Vanessa Tenet

Overweight as an avoidable cause of cancer in Europe

There is growing evidence that excess body weight increases the risk of cancer at several sites, including kidney, endometrium, colon, prostate, gallbladder and breast in post‐menopausal women. The proportion of all cancers attributable to overweight has, however, never been systematically estimated. We reviewed the epidemiological literature and quantitatively summarised, by meta‐analysis, the relationship between excess weight and the risk of developing cancer at the 6 sites listed above. Estimates were then combined with sex‐specific estimates of the prevalence of overweight [body mass index (BMI) 25–29 kg/m2] and obesity (BMI ≥30 kg/m2) in each country in the European Union to obtain the proportion of cancers attributable to excess weight. Overall, excess body mass accounts for 5% of all cancers in the European Union, 3% in men and 6% in women, corresponding to 27,000 male and 45,000 female cancer cases yearly. The attributable proportion varied, in men, between 2.1% for Greece and 4.9% for Germany and, in women, between 3.9% for Denmark and 8.8% for Spain. The highest attributable proportions were obtained for cancers of the endometrium (39%), kidney (25% in both sexes) and gallbladder (25% in men and 24% in women). The largest number of attributable cases was for colon cancer (21,500 annual cases), followed by endometrium (14,000 cases) and breast (12,800 cases). Some 36,000 cases could be avoided by halving the prevalence of overweight and obese people in Europe.

Risk of hematological malignancies among Chernobyl liquidators

Abstract Kesminiene, A., Evrard, A-S., Ivanov, V. K., Malakhova, I. V., Kurtinaitis, J., Stengrevics, A., Tekkel, M., Anspaugh, L. R., Bouville, A., Chekin, S., Chumak, V. V., Drozdovitch, V., Gapanovich, V., Golovanov, I., Hubert, P., Illichev, S. V., Khait, S. E., Kryuchkov, V. P., Maceika, E., Maksyoutov, M., Mirkhaidarov, A. K., Polyakov, S., Shchukina, N., Tenet, V., Tserakhovich, T. I., Tsykalo, A., Tukov, A. R. and Cardis, E. Risk of Hematological Malignancies among Chernobyl Liquidators. Radiat. Res. 170, 721–735 (2008). A case-control study of hematological malignancies was conducted among Chernobyl liquidators (accident recovery workers) from Belarus, Russia and Baltic countries to assess the effect of low- to medium-dose protracted radiation exposures on the relative risk of these diseases. The study was nested within cohorts of liquidators who had worked around the Chernobyl plant in 1986–1987. A total of 117 cases [69 leukemia, 34 non-Hodgkin lymphoma (NHL) and 14 other malignancies of lymphoid and hematopoietic tissue] and 481 matched controls were included in the study. Individual dose to the bone marrow and uncertainties were estimated for each subject. The main analyses were restricted to 70 cases (40 leukemia, 20 NHL and 10 other) and their 287 matched controls with reliable information on work in the Chernobyl area. Most subjects received very low doses (median 13 mGy). For all diagnoses combined, a significantly elevated OR was seen at doses of 200 mGy and above. The excess relative risk (ERR) per 100 mGy was 0.60 [90% confidence interval (CI) −0.02, 2.35]. The corresponding estimate for leukemia excluding chronic lymphoid leukemia (CLL) was 0.50 (90% CI −0.38, 5.7). It is slightly higher than but statistically compatible with those estimated from A-bomb survivors and recent low-dose-rate studies. Although sensitivity analyses showed generally similar results, we cannot rule out the possibility that biases and uncertainties could have led to over- or underestimation of the risk in this study.

Prevalence and determinants of human papillomavirus infection and cervical lesions in HIV-positive women in Kenya.

Background:We assessed the association of human papillomavirus (HPV) infection and cervical intraepithelial neoplasia (CIN) with various characteristics, CD4 count and use of combination antiretroviral therapy (cART) among HIV-positive women.Methods:Cross-sectional study of 498 HIV-positive women who underwent HPV PCR-based testing, cytology, and systematic cervical biopsy.Results:In all, 68.7% of women were HPV-positive, 52.6% had high-risk (hr) HPV, and 40.2% multiple type infections. High-risk human papillomavirus-positivity did not vary significantly by age but it was negatively associated with education level. The most frequent types in 113 CIN2/3 were HPV16 (26.5%), HPV35 (19.5%), and HPV58 (12.4%). CD4 count was negatively associated with prevalence of hrHPV (P<0.001) and CIN2/3 among non-users of cART (P=0.013). Combination antiretroviral therapies users (⩾2 year) had lower hrHPV prevalence (prevalence ratio (PR) vs non-users=0.77, 95% confidence interval (CI): 0.61–0.96) and multiple infections (PR=0.68, 95% CI: 0.53–0.88), but not fewer CIN2/3. The positive predictive value of hrHPV-positivity for CIN2/3 increased from 28.9% at age <35 years to 53.3% in ⩾45 years.Conclusion:The burden of hrHPV and CIN2/3 was high and it was related to immunosuppression level. Combination antiretroviral therapies ( ⩾2 year) use had a favourable effect on hrHPV prevalence but cART in our population may have been started too late to prevent CIN2/3.

Prevalence of human papillomavirus in women with invasive cervical carcinoma by HIV status in Kenya and South Africa.

Data on the prevalence of human papillomavirus (HPV) types in cervical carcinoma in women with HIV are scarce but are essential to elucidate the influence of immunity on the carcinogenicity of different HPV types, and the potential impact of prophylactic HPV vaccines in populations with high HIV prevalence. We conducted a multicentre case–case study in Kenya and South Africa. During 2007–2009, frozen tissue biopsies from women with cervical carcinoma were tested for HPV DNA using GP5+/6+‐PCR assay. One hundred and six HIV‐positive (mean age 40.8 years) and 129 HIV‐negative women (mean age 45.7) with squamous cell carcinoma were included. Among HIV‐positive women, the mean CD4 count was 334 cells/μL and 48.1% were on combined antiretroviral therapy. HIV‐positive women had many more multiple HPV infections (21.6% of HPV‐positive carcinomas) compared with HIV‐negative women (3.3%) (p < 0.001) and the proportion of multiple infections was inversely related to CD4 level. An excess of HPV18 of borderline statistical significance was found in HIV‐positive compared with HIV‐negative cases (Prevalence ratio (PR) = 1.9, 95% confidence interval (CI): 1.0–3.7, adjusted for study centre, age and multiplicity of infection). HPV16 and/or 18 prevalence combined, however, was similar in HIV‐positive (66.7%) and HIV‐negative cases (69.1%) (PR = 1.0, 95% CI: 0.9–1.2). No significant difference was found for other HPV types. Our data suggest that current prophylactic HPV vaccines against HPV16 and 18 may prevent similar proportions of cervical SCC in HIV‐positive as in HIV‐negative women provided that vaccine‐related protection is sustained after HIV infection.

Risk of Thyroid Cancer among Chernobyl Liquidators

After the Chernobyl accident in 1986, the “liquidators” or clean-up workers were among those who received the highest radiation doses to the thyroid from external radiation. Some were also exposed to radioiodines through inhalation or ingestion. A collaborative case-control study nested within cohorts of Belarusian, Russian and Baltic liquidators was conducted to evaluate the radiation-induced risk of thyroid cancer. The study included 107 cases and 423 controls. Individual doses to the thyroid from external radiation and from iodine-131 (131I) were estimated for each subject. Most subjects received low doses (median 69 mGy). A statistically significant dose-response relationship was found with total thyroid dose. The Excess Relative Risk (ERR) per 100 mGy was 0.38 [95% confidence interval (CI): 0.10, 1.09]. The risk estimates were similar when doses from 131I and external radiation were considered separately, although for external radiation the ERR was not statistically significantly elevated. The ERR was similar for micro carcinomas and larger size tumors, and for tumors with and without lymph node involvement. Although recall bias and uncertainties in doses could have affected the magnitude of the risk estimates, the findings of this study contribute to a better characterization the risk of thyroid cancer after radiation exposure in adulthood.

Contribution of ATM and FOXE1 (TTF2) to risk of papillary thyroid carcinoma in Belarusian children exposed to radiation

A dramatic increase in the incidence of papillary thyroid carcinoma (PTC) after childhood exposure to ionizing radiation from the Chernobyl nuclear accident has been described as the largest number of tumors of one type due to one cause that have ever occurred. inter‐individual variations in response to radiation have been documented and the role of genetics in sporadic PTC is well established, suggesting that genetic factors may also affect the risk of radiation‐related PTC. To investigate how environmental and host factors interplay to modify PTC risk, we genotyped 83 cases and 324 matched controls sampled from children living in the area contaminated by fallout from the Chernobyl power plant accident for 19 polymorphisms previously associated with PTC, thyroid biology or radiation‐induced second primary tumors. Significant association with PTC was found for rs1801516 (D1853N) in ATM (odds ratio (OR) = 0.34, 95% confidence interval (CI) 0.16, 0.73) and rs1867277 in the promoter region of FOXE1 (OR = 1.55, 95% CI 1.03, 2.34). Analysis of additional polymorphisms confirmed the association between these two genes and PTC. Our findings suggest that both DNA double‐strand break repair pathway and thyroid morphogenesis pathway or dysregulation of thyroid differentiated state maintenance are involved in the etiology of PTC, and that the studied genetic polymorphisms and radiation dose appear to act as independent multiplicative risk factors for PTC.

RECONSTRUCTION OF RADIATION DOSES IN A CASE-CONTROL STUDY OF THYROID CANCER FOLLOWING THE CHERNOBYL ACCIDENT

A population-based case-control study of thyroid cancer was carried out in contaminated regions of Belarus and Russia among persons who were exposed during childhood and adolescence to fallout from the Chernobyl accident. For each study subject, individual thyroid doses were reconstructed for the following pathways of exposure: (1) intake of 131I via inhalation and ingestion; (2) intake of short-lived radioiodines (132I, 133I, and 135I) and radiotelluriums (131mTe, 132Te) via inhalation and ingestion; (3) external dose from radionuclides deposited on the ground; and (4) ingestion of 134Cs and 137Cs. A series of intercomparison exercises validated the models used for reconstruction of average doses to populations of specific age groups as well as of individual doses. Median thyroid doses from all factors for study subjects were estimated to be 0.37 and 0.034 Gy in Belarus and Russia, respectively. The highest individual thyroid doses among the subjects were 10.2 Gy in Belarus and 5.3 Gy in Russia. Iodine-131 intake was the main pathway for thyroid exposure. Estimated doses from short-lived radioiodines and radiotelluriums ranged up to 0.53 Gy. Reconstructed individual thyroid doses from external exposure ranged up to 0.1 Gy, while those from internal exposure due to ingested cesium did not exceed 0.05 Gy. The uncertainty of the reconstructed individual thyroid doses, characterized by the geometric standard deviation, varies from 1.7 to 4.0 with a median of 2.2.

Prevalence of human papillomavirus types in cervical lesions from women in rural Western India

Cervical cancer is the most common cancer among women in many areas of India which contributes for a fifth of the global burden of disease. Persistent infection with one of the high‐risk human papillomaviruses (HPV) has been established as the cause for cervical cancer and the documentation of the prevalence of HPV types in cervical cancer in different regions of India is useful for a prevention program combining both screening and vaccination. In this study, the HPV type distribution and the frequency of p16INK4a immunoexpression have been determined in 125 cases of inflammatory lesions or grade 1 cervical intraepithelial neoplasia, 74 cases of grade 2, 72 cases of grade 3, and 113 cervical cancer cases diagnosed among women from rural Solapur and Osmanabad districts, Maharashtra. The overall prevalence of high‐risk HPV was 37.6% in inflammatory lesions or grade 1 cervical intraepithelial neoplasia, 63.5% in grade 2, 97.2% in grade 3 and 92% in cervical cancer cases. HPV 16 and HPV 18 were detected in 80.6% of grade 3 cervical intraepithelial neoplasia and 86.5% of cervical cancer cases. 94.7% of the cervical cancer and 84.4% of the high grade lesions with a strong and full thickness staining for p16INK4a were positive for HPV infection; p16INK4a immunoexpression increased with worsening grade of cervical intraepithelial neoplasia. The HPV genotyping data showing a high HPV 16 and 18 prevalence in cancer specimens indicate that prophylactic HPV 16/18 vaccination would have a significant impact on the prevention of cervical cancer in India. J. Med. Virol. 84: 1054–1060, 2012.

Studies of cancer risk among Chernobyl liquidators: materials and methods

The current paper presents the methods and design of two case-control studies among Chernobyl liquidators-one of leukaemia and non-Hodgkin lymphoma, the other of thyroid cancer risk-carried out in Belarus, Estonia, Latvia, Lithuania and Russia. The specific objective of these studies is to estimate the radiation induced risk of these diseases among liquidators of the Chernobyl accident, and, in particular, to study the effect of exposure protraction and radiation type on the risk of radiation induced cancer in the low-to-medium- (0-500 mSv) radiation dose range. The study population consists of the approximately 10000 Baltic, 40000 Belarus and 51 000 Russian liquidators who worked in the 30 km zone in 1986-1987, and who were registered in the Chernobyl registry of these countries. The studies included cases diagnosed in 1993-1998 for all countries but Belarus, where the study period was extended until 2000. Four controls were selected in each country from the national cohort for each case, matched on age, gender and region of residence. Information on study subjects was obtained through face-to-face interview using a standardised questionnaire with questions on demographic factors, time, place and conditions of work as a liquidator and potential risk and confounding factors for the tumours of interest. Overall, 136 cases and 595 controls after receiving their consent were included in the studies. A method of analytical dose reconstruction has been developed, validated and applied to the estimation of doses and related uncertainties for all the subjects in the study. Dose-response analyses are underway and results are likely to have important implications to assess the adequacy of existing protection standards, which are based on risk estimates derived from analyses of the mortality of atomic bomb survivors and other high dose studies.

Comparison of HPV DNA testing in cervical exfoliated cells and tissue biopsies among HIV-positive women in Kenya

HIV‐positive women are infected with human papillomavirus (HPV) (especially with multiple types), and develop cervical intraepithelial neoplasia (CIN) and cervical cancer more frequently than HIV‐negative women. We compared HPV DNA prevalence obtained using a GP5+/6+ PCR assay in cervical exfoliated cells to that in biopsies among 468 HIV‐positive women from Nairobi, Kenya. HPV prevalence was higher in cells than biopsies and the difference was greatest in 94 women with a combination normal cytology/normal biopsy (prevalence ratio, PR = 3.7; 95% confidence interval, CI: 2.4–5.7). PR diminished with the increase in lesion severity (PR in 58 women with high‐grade squamous intraepithelial lesions (HSIL)/CIN2–3 = 1.1; 95% CI: 1.0–1.2). When HPV‐positive, cells contained 2.0‐ to 4.6‐fold more multiple infections than biopsies. Complete or partial agreement between cells and biopsies in the detection of individual HPV types was found in 91% of double HPV‐positive pairs. The attribution of CIN2/3 to HPV16 and/or 18 would decrease from 37.6%, when the presence of these types in either cells or biopsies was counted, to 20.2% when it was based on the presence of HPV16 and/or 18 (and no other types) in biopsies. In conclusion, testing HPV on biopsies instead of cells results in decreased detection but not elimination of multiple infections in HIV‐positive women. The proportion of CIN2/3 attributable to HPV16 and/or 18 among HIV‐positive women, which already appeared to be lower than that in HIV‐negative, would then further decrease. The meaning of HPV detection in cells and random biopsy from HIV‐positive women with no cervical abnormalities remains unclear.