Longitudinal changes of the femoral bone mineral density from first to third trimester of pregnancy: bone health assessment by means of non-ionizing REMS technology.

BACKGROUND: Throughout the pregnancy, there is a substantial transfer of calcium from the maternal skeleton to the fetus, which leads to a transient net reduction of the maternal bone mineral density. AIMS: To assess longitudinally the changes in the bone mineral density at the femoral neck between the first and third trimester of pregnancy in a cohort of healthy participants using Radiofrequency Echographic Multi Spectrometry (REMS) technology. METHODS: Prospective, cohort study conducted at the University hospital of Parma, Italy between July 2022 and February 2023. We recruited healthy participants with an uncomplicated singleton pregnancy before 14 completed weeks of gestation. All included participants were submitted to a sonographic examination of the femoral neck to assess the bone mineral density (and the corresponding Z-score values) using REMS at 11-13 and 36-38 weeks of pregnancy. The primary outcome was the change in the bone mineral density values at the maternal femoral neck between the first and third trimester of pregnancy. RESULTS: Over a period of 7 months, a total of 65 participants underwent bone mineral density measurement at the femoral neck at first and third trimester of the pregnancy using REMS. A significant reduction of the bone mineral density at the femoral neck (0.723 ± 0.069 vs 0.709 ± 0.069 g/cm2; p < 0.001) was noted with a mean bone mineral density change of - 1.9 ± 0.6% between the first and third trimester of pregnancy. At multivariable linear regression analysis, none of the demographic or clinical variables of the study population proved to be independently associated with the maternal bone mineral density changes at the femoral neck. CONCLUSIONS: Our study conducted on a cohort of healthy participants with uncomplicated pregnancy demonstrates that there is a significant reduction of bone mineral density at femoral neck from early to late gestation.

Fragility Score: a REMS-based indicator for the prediction of incident fragility fractures at 5 years.

BACKGROUND: Accurate estimation of the imminent fragility fracture risk currently represents a challenging task. The novel Fragility Score (FS) parameter, obtained during a Radiofrequency Echographic Multi Spectrometry (REMS) scan of lumbar or femoral regions, has been developed for the non-ionizing estimation of skeletal fragility. AIMS: The aim of this study was to assess the performance of FS in the early identification of patients at risk for incident fragility fractures with respect to bone mineral density (BMD) measurements. METHODS: Data from 1989 Caucasians of both genders were analysed and the incidence of fractures was assessed during a follow-up period up to 5 years. The diagnostic performance of FS to discriminate between patients with and without incident fragility fracture in comparison to that of the BMD T-scores measured by both Dual X-ray Absorptiometry (DXA) and REMS was assessed through ROC analysis. RESULTS: Concerning the prediction of generic osteoporotic fractures, FS provided AUC = 0.811 for women and AUC = 0.780 for men, which resulted in AUC = 0.715 and AUC = 0.758, respectively, when adjusted for age and body mass index (BMI). For the prediction of hip fractures, the corresponding values were AUC = 0.780 for women and AUC = 0.809 for men, which became AUC = 0.735 and AUC = 0.758, respectively, after age- and BMI-adjustment. Overall, FS showed the highest prediction ability for any considered fracture type in both genders, resulting always being significantly higher than either T-scores, whose AUC values were in the range 0.472-0.709. CONCLUSION: FS displayed a superior performance in fracture prediction, representing a valuable diagnostic tool to accurately detect a short-term fracture risk.

Pulse-Echo Measurements of Bone Tissues. Techniques and Clinical Results at the Spine and Femur.

The aim of this chapter is to review the available pulse-echo approaches for the quantitative evaluation of bone health status, with a specific application to the assessment of possible osteoporosis presence and to the fracture risk prediction. Along with a review of the main in-vivo imaging approaches for skeletal robustness evaluation and fracture risk assessment, further understanding into Radiofrequency Echographic Multi Spectrometry (REMS), an ultrasound-based method measuring clinically relevant bone districts (i.e. lumbar vertebrae and proximal femur), is provided, and the further potentialities of this technology are discussed.Currently, the bone mineral density (BMD) provided by dual X-ray absorptiometry (DXA) is considered an established indicator for osteoporosis status assessment and fracture risk prediction, however, in order to obtain more accurate results, an additional step beyond BMD would be necessary, which means including data on bone quality for an improved evaluation of the disease and its consequences.REMS is a technology which allows both osteoporosis diagnosis, through the BMD estimation, and the prediction of fracture risk, through the computation of the Fragility Score; both measures are obtained by the automatic processing of unfiltered ultrasound signals acquired in correspondence of anatomical reference sites.

New perspectives in echographic diagnosis of osteoporosis on hip and spine.

Currently, the accepted "gold standard" method for bone mineral density (BMD) measurement and osteoporosis diagnosis is dual-energy X-ray absorptiometry (DXA). However, actual DXA effectiveness is limited by several factors, including intrinsic accuracy uncertainties and possible errors in patient positioning and/or post-acquisition data analysis. DXA employment is also restricted by the typical issues related to ionizing radiation employment (high costs, need of dedicated structures and certified operators, unsuitability for population screenings). The only commercially-available alternative to DXA is represented by "quantitative ultrasound" (QUS) approaches, which are radiation-free, cheaper and portable, but they cannot be applied on the reference anatomical sites (lumbar spine and proximal femur). Therefore, their documented clinical usefulness is restricted to calcaneal applications on elderly patients (aged over 65 y), in combination with clinical risk factors and only for the identification of healthy subjects at low fracture risk. Literature-reported studies performed some QUS measurements on proximal femur, but their clinical translation is mostly hindered by intrinsic factors (e.g., device bulkiness). An innovative ultrasound methodology has been recently introduced, which performs a combined analysis of B-mode images and corresponding "raw" radiofrequency signals acquired during an echographic scan of the target reference anatomical site, providing two novel parameters: Osteoporosis Score and Fragility Score, indicative of BMD level and bone strength, respectively. This article will provide a brief review of the available systems for osteoporosis diagnosis in clinical routine contexts, followed by a synthesis of the most promising research results on the latest ultrasound developments for early osteoporosis diagnosis and fracture prevention.

Automatic measurement of head-perineum distance during intrapartum ultrasound: description of the technique and preliminary results.

OBJECTIVES: To evaluate the accuracy and reliability of a new ultrasound technique for the automatic assessment of the head-perineum distance (HPD) during childbirth. METHODS: HPD was measured on a total of 40 acquisition sessions in 30 laboring women both automatically by an innovative algorithm and manually by trained sonographers, assumed as gold standard. RESULTS: A significant correlation was found between manual and automatic measurements (Intra-CC = 0.994). High values of the coefficient of determination (r2=0.98) and low residual errors: RMSE = 2.01 mm (4.9%) were found. CONCLUSION: The automatic algorithm for the assessment of the HPD represents a reliable technique.

Marriage and parenthood among childhood cancer survivors: a report from the Italian AIEOP Off-Therapy Registry.

BACKGROUND: The aim of this study was to describe the patterns of marriage and parenthood in a cohort of childhood cancer survivors included in the Off-Therapy Registry maintained by the Italian Association of Pediatric Hematology and Oncology. DESIGN AND METHODS: We analyzed a cohort of 6,044 patients diagnosed with cancer between 1960 and 1998, while aged 0 to 14 years and who were 18 years old or older by December 2003. They were followed up through the regional vital statistics registers until death or the end of follow up (October 30, 2006), whichever occurred first, and their marital status and date of birth of their children were recorded. The cumulative probabilities of being married and having a first child were computed by gender and compared by tumor type within the cohort. Marriage and fertility rates (the latter defined as the number of live births per woman-year) were compared with those of the Italian population of the same age, gender, area of residence and calendar period by means of the observed to expected (O/E) ratios. RESULTS: During the follow-up period, 4,633 (77%) subjects had not married. The marriage O/E ratios were 0.56 (95% CI: 0.51-0.61) and 0.70 (95% CI: 0.65-0.76) among men and women, respectively. Overall, 263 men had 367 liveborn children, and 473 women had 697 liveborn children. The female fertility O/E ratio was 0.57 (95% CI: 0.53-0.62) overall, and 1.08 (95% CI: 0.99-1.17) when analyses were restricted to married/cohabiting women CONCLUSIONS: Childhood cancer survivors are less likely to marry and to have children than the general population, confirming the life-long impact of their previous disease on their social behavior and choices. The inclusion of counseling in the strategies of management and long-term surveillance of childhood cancer patients could be beneficial to survivors as they approach adulthood.

The cancer burden and cancer control in developing countries.

Substantial changes in large parts of the developing world have materialised in the last three decades. These are extremely diverse countries with respect to culture, societal values and political arrangements, but sharing one feature--prevalent poverty and limited resources to protect the health of individuals. The control of emerging chronic diseases in low-resource countries is a formidable challenge. For this reason any intervention should be kept logistically simple and incorporated into a general plan aiming at building gradually the infrastructure that is necessary to bring care to the population at large. The present contribution summarizes some of the priorities in cancer prevention in developing countries and the underlying evidence base, and addresses some of the challenges.

The role of parents, friends and teachers in adolescents' cigarette smoking and tombak dipping in Sudan.

OBJECTIVE: To assess the influence of smoking and tombak (local smokeless tobacco) dipping by parents, teachers and friends on cigarette smoking and tombak dipping by school-going Sudanese adolescents. METHODS: This was a school-based cross-sectional survey was conducted in 2005-2006. Logistic regression was used for the analysis. A total of 4277 Sudanese school-going adolescents (aged 11-17 years) from 23 schools who completed an anonymous self-administered questionnaire on the use of tobacco products. Main outcome measures were self-reported tobacco use during the previous month defined current tobacco use. Ever smoking, tombak dipping and other tobacco products were also considered as outcomes. RESULTS: After adjusting for sex, age and school grade, adolescents' smoking habits were strongly associated with the habit in their parents and friends and, more weakly, with tombak dipping by teachers. When adjusted for each other, the association with smoking in friends was unaffected and remained significant (prevalence OR (POR) of having ever smoked was 1.94, 95% CI 1.64 to 2.29; OR of being current smoker was 3.77, 95% CI 2.80 to 5.07). Tobacco smoking in friends was positively associated with adolescents ever tombak dipping (POR 1.81, 95% CI 1.41 to 2.33) and current dipping (OR 3.33, 95% CI 2.20 to 5.05). The association with parental habits was reduced but still significantly elevated. Tombak dipping by teachers was only associated with adolescents ever tobacco smoking. CONCLUSIONS: Tobacco use by parents, teachers and friends was associated with adolescents' tobacco habits. The influence of friends was the strongest. In developing programmes against adolescents' tobacco habits, there is need to target the influence of these 'significant others'. Sudan needs to develop and implement comprehensive anti-smoking and anti-tombak dipping legislation to reduce the growing prevalence of such habits.

First assessment of bone mineral density in healthy pregnant women by means of Radiofrequency Echographic Multi Spectrometry (REMS) technology.

OBJECTIVE: The maternal bone structure is the largest calcium reserve for the fetus during pregnancy, and this is claimed to lead to a bone mineral density (BMD) reduction in pregnant women. The primary outcome of the present work was to assess the BMD in a group of healthy pregnant women. STUDY DESIGN: In this prospective case - control observational study, a non-consecutive group of pregnant women with uncomplicated pregnancy at or >37 weeks were enrolled at the unit of Obstetrics and Gynecology, University of Parma, from February to December 2020. The study subjects were submitted to a sonographic examination of the proximal femur with Radiofrequency Echographic Multi Spectrometry (REMS) technology to quantify the BMD of the femur. The BMD values obtained in the study group were compared with those of a control group of non-pregnant women matched for age, ethnicity and pre-pregnant body mass index (BMI). RESULTS: Overall, 78 pregnant women at 39.1 ±â€¯1.5 weeks were assessed. Compared with non-pregnant women, the femoral BMD values measured in pregnancy using REMS were significant lower (0.769 ±â€¯0.094 g/cm2 vs 0.831 ±â€¯0.101 g/cm2, p = 0.0001) with a mean BMD reduction of 8.1%. The femoral neck BMD presented a positive correlation with the pre-pregnant BMI (p = 0.0004) and a negative correlation with the maternal age (p < 0.0001). In addition, a lower femoral neck BMD in Caucasian ethnicity compared with non-Caucasian was noted (p < 0.0001). CONCLUSION: In this exploratory and proof of concept study, for the first time, a decreased BMD has been objectively demonstrated in pregnant compared with non-pregnant women by means of REMS technology. New studies are required to assess the longitudinal changes of maternal bone density throughout the pregnancy.

Risk factors for breast cancer among Filipino women in Manila.

Age-adjusted incidence rates of breast cancer vary greatly worldwide with highest rates found in the typically 'westernised' countries of North America and Europe. Much lower rates are observed in Asian and African populations but an exception to this has been reported for the Manila Cancer Registry in the Philippines. The reason for this high rate is unknown but may be associated with the change in lifestyle that has occurred in urban Manila since the 1960s. In 1995, a randomised controlled trial was set up in Manila to evaluate the feasibility of a screening intervention by clinical breast examination as an alternative to mammography. The cohort of 151,168 women was followed-up to 2001 for cancer incidence and a nested case-control study carried out. This aimed to evaluate the increase in breast cancer risk associated with known risk factors. Increased risks were seen for a high level of education (OR = 1.9 95%CI 1.1-3.3 for education stopped at > or =13 versus <13 years), nulliparity (OR = 5.0 95% CI 2.5-10.0 for nulliparity versus five or more children), and late age at first birth (OR = 3.3 95% CI 1.3-8.3 for age > or =30 versus <20 years). We found no association with excess body weight, height, use of exogenous hormones or alcohol consumption. From this study, the recognised "classical" risk factors do not fully explain the high breast cancer incidence in Metro Manila, especially when compared to other urban Asian populations. We conclude that it is too simplistic to ascribe the high risk to 'westernisation'.

Minimally invasive video-assisted thyroidectomy (MIVAT): what is the real advantage?

BACKGROUND: The evolution of video-assisted or laparoscopic surgical techniques in the last several years has changed the surgical treatment approach to many diseases, also in endocrine surgery. MATERIALS AND METHODS: From July 2005 to March 2009, we treated 211 patients with minimally invasive video-assisted thyroidectomy (MIVAT). The procedure was performed in accordance with Miccoli's technique using an Ultracision CS 14 (Ethicon Endosurgery) and/or Single Use Automatic Clip Applier S-90 (Autosuture). In all cases, we recorded the incidence of postoperative hypocalcaemia as a serum calcium value lower than 8 mg/dl with or without hypocalcaemic symptoms, postoperative haemorrhage or nerve palsy, mean operative time. All patients were also assessed for postoperative pain and given a visual analogue score from 0 to 10 at 1 and 24 h after surgery. We matched these results with a group of 587 patients treated during the same period with traditional thyroidectomy. RESULTS: The female/male ratio was 4:1; the mean age of the patients was 50.6 years. In the MIVAT group, the mean time of surgical procedure decreased by 52.4 min. We observed 16 hypocalcaemic cases with clinical symptoms (7.58%) (six of these cases were published in a previous article and were among the first 100 cases treated) and 59 cases of serologic hypocalcaemia (27.9%) (serum calcium lower than 8 mg/dl); the mean value of calcium concentration was 7.5 +/- 0.27 mg/dl. We observed six cases of monolateral nerve palsy, and after 6 months, a definitive palsy in two cases (0.9%); these two cases were in the first 25 cases treated. Comparisons with traditional thyroidectomy group showed statistically significant differences in postoperative serologic hypocalcaemia (p < 0.001), no difference in mean calcium value (p = 0.41) and no statistical difference in the incidences of nerve palsy and haemorrhage. CONCLUSIONS: Patients treated with MIVAT showed an improvement in incidence of postoperative hypocalcaemia, postoperative pain, postoperative stay, psychophysical recovery and cosmetic result.

CYP1A1, GSTM1, and GSTT1 polymorphisms, smoking, and lung cancer risk in a pooled analysis among Asian populations.

To evaluate the roles of CYP1A1 polymorphisms [Ile 462Val and T 6235C (MspI)] and deletion of GSTM1 and GSTT1 in lung cancer development in Asian populations, a pooled analysis was conducted on 13 existing studies included in Genetic Susceptibility to Environmental Carcinogenesis database. This pooled analysis included 1,971 cases and 2,130 controls. Lung cancer risk was estimated as odds ratios (OR) and 95% confidence intervals (95% CI) using unconditional logistic regression model adjusting for age, sex, and pack-year. The CYP1A1 6235C variant was associated with squamous cell lung cancer (TC versus TT: OR, 1.42; 95% CI, 0.96-2.09; CC versus TT: OR, 1.97; 95% CI, 1.26-3.07; P trend = 0.003). In haplotype analysis, 462Val-6235T and Ile-C haplotypes were associated with lung cancer risk with reference to the Ile-T haplotype (OR, 3.41; 95% CI, 1.78-6.53 and OR, 1.39; 95% CI, 1.12-1.71, respectively). The GSTM1-null genotype increased squamous cell lung cancer risk (OR, 1.36; 95% CI, 1.05-1.77). When the interaction was evaluated with smoking, increasing trend of lung cancer risk as pack-year increased was stronger among those with the CYP1A1 6235 TC/CC genotype compared with those with TT genotype (P interaction = 0.001) and with the GSTM1-null genotype compared with the present type (Pinteraction = 0.08, when no genotype effect with no exposure was assumed). These results suggest that genetic polymorphisms in CYP1A1 and GSTM1 are associated with lung cancer risk in Asian populations. However, further investigation is warranted considering the relatively small sample size when subgroup analyses were done and the lack of environmental exposure data other than smoking.

Hyper-insulinaemia and cancer, meta-analyses of epidemiological studies.

BACKGROUND: A substantial body of evidence links sex hormones, diet, excess body weight and physical activity to the risk of developing cancer at several sites common in affluent countries. The hypothesis that high circulating levels of insulin could be the underlying factor increasing cancer risk has been proposed. Epidemiological studies on markers of hyper-insulinaemia and cancer are reviewed and summarized. METHODS: Studies of cancers of the colon and rectum, pancreas, breast, and endometrium examining the association with blood levels of C-peptide, insulin, glucose, glycated haemoglobin (HbA1c) were searched in PubMed. Multivariate, adjusted relative risks (RR) and their 95% confidence intervals were abstracted and summarized by meta-analyses. RESULTS: Most of the studies identified were cohorts that relied on measurements obtained at baseline or assessed in blood stored at low temperature several years before the onset of cancer. The meta-analyses showed excess risks of colorectal and pancreatic cancers associated with higher levels of circulating C-peptide/insulin and with markers of glycaemia. Significant heterogeneity was found among four epidemiological studies of endometrial cancer and C-peptide giving a summary RR compatible with no association. Overall breast cancer risk was significantly higher in the upper categories of C-peptide/insulin, however, the excess derived entirely from retrospective studies. CONCLUSION: Current evidence suggests that subjects who develop colorectal and pancreatic cancers have increased pre-diagnostic blood levels of insulin and glucose.

Di- and tripeptide transport in vertebrates: the contribution of teleost fish models.

Solute Carrier 15 (SLC15) family, alias H+-coupled oligopeptide cotransporter family, is a group of membrane transporters known for their role in the cellular uptake of di- and tripeptides (di/tripeptides) and peptide-like molecules. Of its members, SLC15A1 (PEPT1) chiefly mediates intestinal absorption of luminal di/tripeptides from dietary protein digestion, while SLC15A2 (PEPT2) mainly allows renal tubular reabsorption of di/tripeptides from ultrafiltration, SLC15A3 (PHT2) and SLC15A4 (PHT1) possibly interact with di/tripeptides and histidine in certain immune cells, and SLC15A5 has unknown function. Our understanding of this family in vertebrates has steadily increased, also due to the surge of genomic-to-functional information from 'non-conventional' animal models, livestock, poultry, and aquaculture fish species. Here, we review the literature on the SLC15 transporters in teleost fish with emphasis on SLC15A1 (PEPT1), one of the solute carriers better studied amongst teleost fish because of its relevance in animal nutrition. We report on the operativity of the transporter, the molecular diversity, and multiplicity of structural-functional solutions of the teleost fish orthologs with respect to higher vertebrates, its relevance at the intersection of the alimentary and osmoregulative functions of the gut, its response under various physiological states and dietary solicitations, and its possible involvement in examples of total body plasticity, such as growth and compensatory growth. By a comparative approach, we also review the few studies in teleost fish on SLC15A2 (PEPT2), SLC15A4 (PHT1), and SLC15A3 (PHT2). By representing the contribution of teleost fish to the knowledge of the physiology of di/tripeptide transport and transporters, we aim to fill the gap between higher and lower vertebrates.

The surgical approach to nodule Thyr 3-4 after the 2.2014 NCCN and 2015 ATA guidelines.

BACKGROUND: The incidence of palpables thyroid nodules in general population is 5% and the prevalence of non -palpable nodules is higher (35-60%) in the endemic goiter area. In the last years the new guidelines and new classification related to thyroid nodule have changed the indication to treat it. MATERIAL AND METHOD: We analyzed the patients treated from January 2013 to June 2016 for Thyr 3 and Thyr 4 thyroid nodule sec. Bethesda system. We have divided in I and II period related to the 2.2014 and 2015 ATA guidelines and we have evaluated the indication to treat, the type of surgical procedure, the incidence of thyroid carcinoma and the adverse events. RESULTS: We selected from 909 cases, 252 cases surgically treated with preoperative diagnosis of Thyr 3(80 cases) and Thyr 4(172 cases); carcinoma was found in 21/80 (26.2%) and in 62/172 (26.05%). The period was divided from January 2013 to December 2014 and from January 2015 to june 2016 (first and second period). In II period we found carcinoma in 8/40 Thyr3 and in 26/88 Thyr 4. The incidence of lobectomy in II period was higher than I period (p < 0.0001) sec.guidelines indications. No difference in adverse events. The number of cancer is lower in patients treated with lobectomy than those who underwent total thyroidectomy (12,5%vs 21,8% in Thyr 3; 15,3% vs 32% in Thyr 4). CONCLUSIONS: The indications to treat related to Thyr 3 and Thyr4 are changed in the two periods. The number of cancer is lower in patients treated with lobectomy. The new guidelines have changed the surgical approach to thyroid nodule.

GSTM1 and CYP1A1 polymorphisms, tobacco, air pollution, and lung cancer: a study in rural Thailand.

OBJECTIVES: The Lampang Province is situated in the northern region of Thailand. Incidence rates of lung cancer are high for Asian standards, particularly in women. This study was conducted to quantify the risk of lung cancer associated with exposures prevalent in the area and to investigate possible interactions with genetic susceptibility. The presence of several large open-cast coal mines from 1955 close to electricity-generating plants was a particular focus of concern. METHODS: Two-hundred and eleven cases of primary lung cancers diagnosed in 1993 to 1995 and residents in the province were recruited at the Lampang Provincial Hospital (main referral center for treatment of the disease). Two sets of controls, frequency-matched to the cases by sex and age, were recruited (a) from the resident population (202 interviewed) and (b) from patients admitted to the hospital for diseases predominantly unrelated to tobacco smoking (211 interviewed). Sociodemographic information, complete residential history, and characteristics of the household (place of cooking, cooking fuel, and heating fuels), occupational history, and history of tobacco smoking were obtained by interview. Cases and controls ( approximately 50% of the population-based series) provided a blood sample. A point source air pollution exposure index was calculated for each village/township reported in residential histories based on the linear distance from the Mae Moh Center (the area of the electricity-generating plants), the year-specific gaseous (SO(2) and NO(2)) or total suspended particulate emissions from the Mae Moh Power Plant, and the percentage of wind from the center. Odds ratios (OR) for the disease associated with categorical variables were estimated within unconditional logistic regression. Extraction of genomic DNA and genotyping of variants in CYP1A1 and GSTM1 were conducted to assess the extent of modification of risk by these genes that are involved in the metabolism of polycyclic aromatic hydrocarbons, a common component of the exposures. RESULTS: Overall, there was no evidence of relevant differences in the socioeconomic level of the three groups. The two control sets were similar with respect to lifelong tobacco habit and were subsequently pooled in analyses. Never-smokers were 7% of men and 33% of women. Smoking of local traditional products unfiltered and high in tar content is a common habit in the rural female population. ORs associated with smoking increased with duration of the habit and average daily amount, being 4.9 [95% confidence interval (95% CI), 2.5-9.7] for smokers of > or =7 cigarettes/d and 3.3 (95% CI, 1.7-6.2) for duration of 41 years or longer compared with nonsmokers. Smoking of local products was associated with an independent OR of 3.1 (95% CI, 1.7-5.6) adjusted for lifelong cumulative amount of tobacco smoked. Although most smokers had the habit for at least 16 years, the daily consumption was low compared with Western standards. Other potential sources of exposure to lung carcinogens (emission from the power-generating plants and domestic burning of coal and wood for cooking and heating) were not associated with increased risk of lung cancer. None of the three polymorphisms examined increased the risk of lung cancer or modified the risk associated with tobacco smoking. CONCLUSION: In this rural population, 96% of male and 64% of female lung cancer incidence were explained by tobacco smoking. None of the potential sources of air pollution deriving from the combustion of coal and wood, or polymorphisms in the CYP1A1 gene or deletion of the GSTM1 had an effect on the risk of lung cancer, either together or separately.

ATM haplotypes and cellular response to DNA damage: association with breast cancer risk and clinical radiosensitivity.

The ATM gene, mutated in the cancer-prone and radiation-sensitive syndrome ataxia-telangiectasia (AT), could predispose to breast cancer (BC) development and adverse radiotherapy responses. Sixteen ATM variants were genotyped in 254 BC cases, 70 of whom were adverse radiotherapy responders (RS-BC), and 312 control subjects and the ATM haplotypes were constructed. Constitutive ATM protein, cell survival, and the p53 response after exposure to ionizing radiation were compared in lymphoblastoid cell lines (LCLs) established from the BC cases, AT, and normal individuals. The tightly linked intronic ATM polymorphisms IVS22-77 T>C and IVS48 + 238 C>G, in the homozygote state were associated with increased BC risk [IVS22-77 CC versus TT odds ratio (OR), 1.67; 95% confidence interval (CI), 1.00-2.81], and in the heterozygote state with clinical radioprotection (IVS22-77 CT versus TT OR, 0.45; 95% CI, 0.24-0.85). Homozygote carriers of the G5557A variant were over-represented in RS-BC cases compared with non-RS-BC cases (OR, 6.76; 95% CI, 1.19-38.43). These three single nucleotide polymorphisms were associated with the three major ATM haplotypes present in >80% of the study population. BC LCLs treated with ionizing radiation exhibited an intermediate cell survival and p53 response between that of normal and AT LCLs, with the response in the RS-BC LCLs being more compromised than in the non-RS-BC LCLs. Our study suggests a general pattern of increased BC risk associated with carrying any one of the ATM variants studied, with a significant association being observed in individuals carrying variants on both ATM alleles (OR, 1.75; 95% CI, 1.09-2.81) and that ATM variants may impact on radiation sensitivity.