Normative Values for Electrochemical Skin Conductance Measurements for Quantitative Assessment of Sudomotor Function in Healthy Indian Adults.

CONTEXT: Electrochemical skin conductance (ESC) test is a widely accepted objective technique for quantitatively assessing sudomotor dysfunction, which is one of the earliest-detected neurophysiologic abnormalities in diabetic patients with distal symmetric polyneuropathy. AIMS: This study aimed to provide normative data for ESC values among healthy Indian participants and assess the potential influence of age, sex, and body mass index (BMI) on ESC measurements. SETTINGS AND DESIGN: A sample of 217 healthy participants aged 18-75 years were recruited and assessed for parameters including age, gender, BMI, and ESC measurements of the hands and feet. STATISTICAL ANALYSIS USED: The Shapiro-Wilk test was used to assess the normality of the data. Pearson's correlation was used to evaluate the association between age, gender, and BMI, and ESC measurements. RESULTS: The mean age of the participants was 43.3 ± 13.2 years, and mean BMI was 26.0 ± 4.3 kg/m2. Mean ESC for the hands and feet was 68.9 ± 13.1 and 71 ± 12.9 micro-Siemens, respectively, and there was a significant correlation between values from the right and left hands and feet (r = 0.9, P < 0.0001). A significant correlation was also observed between ESC measurements of the hands and feet (r = 0.94, P < 0.0001). ESC values of both hands and feet declined with age. A weak but significant inverse correlation between ESC and age was observed for the hands (r = 0.02, P = 0.01) and for the feet (r = 0.12, P < 0.0001). There was no significant difference in hand or feet ESC measurement between male and female participants. No significant correlation was observed between BMI and ESC of hands or feet. Only age was identified as a significant determinant of ESC on multivariate logistic regression analysis. CONCLUSIONS: Normative values for Indians are lower than that reported for Caucasians.

Quick, non-invasive and quantitative assessment of small fiber neuropathy in patients receiving chemotherapy.

Chemotherapy-induced peripheral neurotoxicity (CIPN) is a common, potentially severe and dose-limiting adverse effect; however, it is poorly investigated at an early stage due to the lack of a simple assessment tool. As sweat glands are innervated by small autonomic C-fibers, sudomotor function testing has been suggested for early screening of peripheral neuropathy. This study aimed to evaluate Sudoscan, a non-invasive and quantitative method to assess sudomotor function, in the detection and follow-up of CIPN. Eighty-eight patients receiving at least two infusions of Oxaliplatin only (45.4%), Paclitaxel only (14.8%), another drug only (28.4%) or two drugs (11.4%) were enrolled in the study. At each chemotherapy infusion the accumulated dose of chemotherapy was calculated and the Total Neuropathy Score clinical version (TNSc) was carried out. Small fiber neuropathy was assessed using Sudoscan (a 3-min test). The device measures the Electrochemical Skin Conductance (ESC) of the hands and feet expressed in microSiemens (µS). For patients receiving Oxaliplatin mean hands ESC changed from 73 ± 2 to 63 ± 2 and feet ESC from 77 ± 2 to 66 ± 3 µS (p < 0.001) while TNSc changed from 2.9 ± 0.5 to 4.3 ± 0.4. Similar results were observed in patients receiving Paclitaxel or another neurotoxic chemotherapy. During the follow-up, ESC values of both hands and feet with a corresponding TNSc < 2 were 70 ± 2 and 73 ± 2 µS respectively while they were 59 ± 1.4 and 64 ± 1.5 µS with a corresponding TNSc ≥ 6 (p < 0.0001 and p = 0.0003 respectively). This preliminary study suggests that small fiber neuropathy could be screened and followed using Sudoscan in patients receiving chemotherapy.

The association of body shape trajectories over the life course with type 2 diabetes risk in adulthood: a group-based modeling approach.

PURPOSE: Low birth weight is a well-recognized risk factor for type 2 diabetes (T2D), but less is known about risks associated with the evolution of body shape throughout life with incident T2D in adulthood. METHODS: In 80,110 women from the Etude Epidémiologique auprès de femmes de la Mutuelle Générale de l'Education Nationale (E3N) cohort study, trajectories of self-reported body shapes from age 8 years to 35-40 years were derived using a group-based modeling approach and studied in relation with incident T2D. RESULTS: Compared with women who maintained a stable midrange body shape trajectory from 8 to 40 years, women in all other observed trajectories were at a higher risk of developing T2D in adulthood: The highest risk was observed for women who were lean at age 8 years and had a sharp increase in body shape (hazards ratio = 2.91 [2.35-3.62]); their T2D risk was higher (P for homogeneity = .059) than for women who maintained the largest body shape (hazards ratio = 2.18 [1.76-2.69]). CONCLUSIONS: A group-based modeling approach has identified trajectories of body shape evolution with different risks of developing T2D in adulthood. A sharp increase in body shape after puberty in previously lean girls is a risk factor for the subsequent development of diabetes.

Alcohol consumption and breast cancer risk subtypes in the E3N-EPIC cohort.

The aim of this study was to obtain an overview of the associations between alcohol consumption and breast cancer risk at adulthood, by type of alcohol and subtype of breast cancer. Between 1993 and 2008, 66,481 women from the French E3N-EPIC cohort were followed up and asked to report their alcohol consumption, by type of alcohol, through a 208-item diet-history questionnaire. A total of 2812 breast cancer cases were validated during the follow-up session. No association was found between high alcohol consumption, whatever its type, and increase in breast cancer risk in the premenopausal period. During the postmenopausal period, a linear association between total alcohol consumption and breast cancer risk was found (P<0.0001), mainly driven by the associations with wine and beer [hazard ratio=1.33 (1.11-1.58) and 1.85 (1.19-2.89)] for more than two glasses per day of wine and beer, respectively, compared with nondrinkers] and with ER+/PR+ breast cancer subtypes. In the postmenopausal period, we observed interactions between total alcohol and folate intake levels (P=0.1192) and BMI (P=0.0367), with higher increased risks observed for high alcohol intake among women with low folate intake or who were overweight or obese. Our results make precise the current body of knowledge on the relationship between alcohol and breast cancer subtypes. Interactions between alcohol and other factors should further be taken into account in public health nutrition programs.

Wine consumption throughout life is inversely associated with type 2 diabetes risk, but only in overweight individuals: results from a large female French cohort study.

Alcohol has previously been shown to have a U-shaped association with type 2 diabetes (T2D) risk, but less is known regarding the specific association with wine. To evaluate for the first time the associations between T2D risk and both baseline wine consumption and trajectories of wine consumption frequency throughout life, estimated using an innovative group-based trajectory modeling strategy. A total of 66,485 women from the French prospective E3N-EPIC cohort were followed between 1993 and 2007; 1,372 incident cases of T2D were diagnosed during the follow-up. Multivariable Cox regression models were used to estimate hazard ratios (HRs) and 95 % confidence intervals (95 % CI) for T2D risk. The average consumption of wine, among alcohol consumers, was 0.81 drinks/day (1 drink = 150 mL). Associations between wine and T2D were restricted to overweight women (P interaction = 0.0084). Among them, wine consumption was inversely associated with T2D risk (P trend = 0.0022). A lower risk was observed for overweight women having two or more drinks/day [HR 0.59 (0.43-0.82)] when compared with non-alcohol consumers. Women who started to drink wine early in life (around age 10-15 years) were at a significantly lower risk than lifetime abstainers. In our study, wine drinking was inversely associated with T2D risk but only in overweight women. Our results also suggest a potential beneficial, cumulative effect of moderate wine consumption throughout life for overweight women, who would already be at higher risk of T2D. We encourage other cohort studies with information on wine consumption to investigate these associations.

Anthropometric features and cutaneous melanoma risk: a prospective cohort study in French women.

BACKGROUND: Epidemiological studies on anthropometric features and cutaneous melanoma risk in women yielded inconsistent results, with few analyses involving prospective cohort data. Our objective was to explore several anthropometric characteristics in relation to the risk of melanoma in women. METHODS: We prospectively analysed data from E3N, a French cohort involving 98,995 women born in 1925-1950. Participants completed self-administered questionnaires sent biennially over 1990-2008. Relative risks (RRs) and 95% confidence intervals (CIs) were computed using Cox proportional hazards regression models, adjusted for age, number of naevi, freckling, skin and hair colour, skin sensitivity to sun exposure, residential sun exposure, and physical activity. RESULTS: Height was positively associated with melanoma in age-adjusted models only (RR=1.27, 95% CI=1.05-1.55 for ≥ 164 cm vs. <160 cm; P for trend=0.02). After full adjustment, there was a significantly positive relationship between sitting-to-standing height ratio and melanoma risk (RR=1.40, 95% CI=1.06-1.86 for ≥ 0.533 vs. <0.518; P for trend=0.02). A large body shape at menarche was inversely associated with the risk of melanoma (RR=0.78, 95% CI=0.62-0.98; compared with lean). However, weight, body mass index, body surface area, waist or hip circumference, sitting height or leg length were not significantly associated with risk. CONCLUSION: These results suggest that height, sitting-to-standing height ratio and body shape at menarche may be associated with melanoma risk. Further research is required to confirm these relationships and better understand the underlying mechanisms.

Risks of endometrial cancer associated with different hormone replacement therapies in the E3N cohort, 1992-2008.

We assessed whether different oral progestogens in hormone replacement therapy may differentially affect the risk of endometrial cancer, using data from the Etude Epidémiologique auprès de femmes de l'Education Nationale (E3N), a French cohort study (1992-2008). Hazard ratios and their confidence intervals were derived from Cox models. Among 65,630 postmenopausal women (mean follow-up: 10.8 years), 301 endometrial cancers occurred. Compared with never use, ever use of estrogen + micronized progesterone was associated with an increased risk of endometrial cancer (hazard ratio (HR) = 1.80, 95% confidence interval (CI): 1.38, 2.34) that was significantly more marked with longer duration of use (for ≤5 years, HR = 1.39 (95% CI: 0.99, 1.97); for >5 years, HR = 2.66 (95% CI: 1.87, 3.77)). Although use of estrogen + dydrogesterone was not associated overall with endometrial cancer risk (HR = 1.05, 95% CI: 0.76, 1.45), there was a significantly increased risk with long-term use compared with never use (for >5 years, HR = 1.69, 95% CI: 1.06, 2.70). Users of preparations containing other progesterone derivatives or a norsteroid derivative were not at significantly increased risk (HR = 0.79 (95% CI: 0.60, 1.05) and HR = 1.30 (95% CI: 0.85, 1.99), respectively). In conclusion, micronized progesterone and, to a lesser extent, dydrogesterone at the doses used in France may not be sufficient to prevent estrogen-induced endometrial cancers.

Association between melanocytic nevi and risk of breast diseases: The French E3N prospective cohort.

BACKGROUND: While melanocytic nevi have been associated with genetic factors and childhood sun exposure, several observations also suggest a potential hormonal influence on nevi. To test the hypothesis that nevi are associated with breast tumor risk, we explored the relationships between number of nevi and benign and malignant breast disease risk. METHODS AND FINDINGS: We prospectively analyzed data from E3N, a cohort of French women aged 40-65 y at inclusion in 1990. Number of nevi was collected at inclusion. Hazard ratios (HRs) for breast cancer and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models. Associations of number of nevi with personal history of benign breast disease (BBD) and family history of breast cancer were estimated using logistic regression. Over the period 15 June 1990-15 June 2008, 5,956 incident breast cancer cases (including 5,245 invasive tumors) were ascertained among 89,902 women. In models adjusted for age, education, and known breast cancer risk factors, women with "very many" nevi had a significantly higher breast cancer risk (HR = 1.13, 95% CI = 1.01-1.27 versus "none"; ptrend = 0.04), although significance was lost after adjustment for personal history of BBD or family history of breast cancer. The 10-y absolute risk of invasive breast cancer increased from 3,749 per 100,000 women without nevi to 4,124 (95% CI = 3,674-4,649) per 100,000 women with "very many" nevi. The association was restricted to premenopausal women (HR = 1.40, ptrend = 0.01), even after full adjustment (HR = 1.34, ptrend = 0.03; phomogeneity = 0.04), but did not differ according to breast cancer type or hormone receptor status. In addition, we observed significantly positive dose-response relationships between number of nevi and history of biopsy-confirmed BBD (n = 5,169; ptrend<0.0001) and family history of breast cancer in first-degree relatives (n = 7,472; ptrend = 0.0003). The main limitations of our study include self-report of number of nevi using a qualitative scale, and self-reported history of biopsied BBD. CONCLUSIONS: Our findings suggest associations between number of nevi and the risk of premenopausal breast cancer, BBD, and family history of breast cancer. More research is warranted to elucidate these relationships and to understand their underlying mechanisms.

Active and passive cigarette smoking and breast cancer risk: results from the EPIC cohort.

Recent cohort studies suggest that increased breast cancer risks were associated with longer smoking duration, higher pack-years and a dose-response relationship with increasing pack-years of smoking between menarche and first full-term pregnancy (FFTP). Studies with comprehensive quantitative life-time measures of passive smoking suggest an association between passive smoking dose and breast cancer risk. We conducted a study within the European Prospective Investigation into Cancer and Nutrition to examine the association between passive and active smoking and risk of invasive breast cancer and possible effect modification by known breast cancer risk factors. Among the 322,988 women eligible for the study, 9,822 developed breast cancer (183,608 women with passive smoking information including 6,264 cases). When compared to women who never smoked and were not being exposed to passive smoking at home or work at the time of study registration, current, former and currently exposed passive smokers were at increased risk of breast cancer (hazard ratios (HR) [95% confidence interval (CI)] 1.16 [1.05-1.28], 1.14 [1.04-1.25] and 1.10 [1.01-1.20], respectively). Analyses exploring associations in different periods of life showed the most important increase in risk with pack-years from menarche to FFTP (1.73 [1.29-2.32] for every increase of 20 pack-years) while pack-years smoked after menopause were associated with a significant decrease in breast cancer risk (HR = 0.53, 95% CI: 0.34-0.82 for every increase of 20 pack-years). Our results provide an important replication, in the largest cohort to date, that smoking (passively or actively) increases breast cancer risk and that smoking between menarche and FFTP is particularly deleterious.

Dietary acid load and risk of type 2 diabetes: the E3N-EPIC cohort study.

AIMS/HYPOTHESIS: The objective of this study was to evaluate the prospective relationship between dietary acid load, assessed with both the potential renal acid load (PRAL) and the net endogenous acid production (NEAP) scores, and type 2 diabetes risk. METHODS: A total of 66,485 women from the E3N-EPIC cohort were followed for incident diabetes over 14 years. PRAL and NEAP scores were derived from nutrient intakes. HRs for type 2 diabetes risk across quartiles of the baseline PRAL and NEAP scores were estimated with multivariate Cox regression models. RESULTS: During follow-up, 1,372 cases of incident type 2 diabetes were validated. In the overall population, the highest PRAL quartile, reflecting a greater acid-forming potential, was associated with a significant increase in type 2 diabetes risk, compared with the first quartile (HR 1.56, 95% CI 1.29, 1.90). The association was stronger among women with BMI <25 kg/m2 (HR 1.96, 95% CI 1.43, 2.69) than in overweight women (HR 1.28, 95% CI 1.00, 1.64); statistically significant trends in risk across quartiles were observed in both groups (p trend < 0.0001 and p trend = 0.03, respectively). The NEAP score provided similar findings. CONCLUSIONS/INTERPRETATION: We have demonstrated for the first time in a large prospective study that dietary acid load was positively associated with type 2 diabetes risk, independently of other known risk factors for diabetes. Our results need to be validated in other populations, and may lead to promotion of diets with a low acid load for the prevention of diabetes. Further research is required on the underlying mechanisms.

Air pollution and lung cancer incidence in 17 European cohorts: prospective analyses from the European Study of Cohorts for Air Pollution Effects (ESCAPE).

BACKGROUND: Ambient air pollution is suspected to cause lung cancer. We aimed to assess the association between long-term exposure to ambient air pollution and lung cancer incidence in European populations. METHODS: This prospective analysis of data obtained by the European Study of Cohorts for Air Pollution Effects used data from 17 cohort studies based in nine European countries. Baseline addresses were geocoded and we assessed air pollution by land-use regression models for particulate matter (PM) with diameter of less than 10 µm (PM10), less than 2·5 µm (PM2·5), and between 2·5 and 10 µm (PMcoarse), soot (PM2·5absorbance), nitrogen oxides, and two traffic indicators. We used Cox regression models with adjustment for potential confounders for cohort-specific analyses and random effects models for meta-analyses. FINDINGS: The 312 944 cohort members contributed 4 013 131 person-years at risk. During follow-up (mean 12·8 years), 2095 incident lung cancer cases were diagnosed. The meta-analyses showed a statistically significant association between risk for lung cancer and PM10 (hazard ratio [HR] 1·22 [95% CI 1·03-1·45] per 10 µg/m(3)). For PM2·5 the HR was 1·18 (0·96-1·46) per 5 µg/m(3). The same increments of PM10 and PM2·5 were associated with HRs for adenocarcinomas of the lung of 1·51 (1·10-2·08) and 1·55 (1·05-2·29), respectively. An increase in road traffic of 4000 vehicle-km per day within 100 m of the residence was associated with an HR for lung cancer of 1·09 (0·99-1·21). The results showed no association between lung cancer and nitrogen oxides concentration (HR 1·01 [0·95-1·07] per 20 µg/m(3)) or traffic intensity on the nearest street (HR 1·00 [0·97-1·04] per 5000 vehicles per day). INTERPRETATION: Particulate matter air pollution contributes to lung cancer incidence in Europe. FUNDING: European Community's Seventh Framework Programme.

Consumption of artificially and sugar-sweetened beverages and incident type 2 diabetes in the Etude Epidemiologique aupres des femmes de la Mutuelle Generale de l'Education Nationale-European Prospective Investigation into Cancer and Nutrition cohort.

BACKGROUND: It has been extensively shown, mainly in US populations, that sugar-sweetened beverages (SSBs) are associated with increased risk of type 2 diabetes (T2D), but less is known about the effects of artificially sweetened beverages (ASBs). OBJECTIVE: We evaluated the association between self-reported SSB, ASB, and 100% fruit juice consumption and T2D risk over 14 y of follow-up in the French prospective Etude Epidémiologique auprès des femmes de la Mutuelle Générale de l'Education Nationale-European Prospective Investigation into Cancer and Nutrition cohort. DESIGN: A total of 66,118 women were followed from 1993, and 1369 incident cases of T2D were diagnosed during the follow-up. Cox regression models were used to estimate HRs and 95% CIs for T2D risk. RESULTS: The average consumption of sweetened beverages in consumers was 328 and 568 mL/wk for SSBs and ASBs, respectively. Compared with nonconsumers, women in the highest quartiles of SSB and ASB consumers were at increased risk of T2D with HRs (95% CIs) of 1.34 (1.05, 1.71) and 2.21 (1.56, 3.14) for women who consumed >359 and >603 mL/wk of SSBs and ASBs, respectively. Strong positive trends in T2D risk were also observed across quartiles of consumption for both types of beverage (P = 0.0088 and P < 0.0001, respectively). In sensitivity analyses, associations were partly mediated by BMI, although there was still a strong significant independent effect. No association was observed for 100% fruit juice consumption. CONCLUSIONS: Both SSB consumption and ASB consumption were associated with increased T2D risk. We cannot rule out that factors other than ASB consumption that we did not control for are responsible for the association with diabetes, and randomized trials are required to prove a causal link between ASB consumption and T2D.

Anthropometrics, body shape over 12 years and risk of cancer events in pre- and post-menopausal women.

Studies of anthropometry and cancer have focused on body mass index (BMI). Relations between weight, waist (WC) and hip circumferences (HC), birth length and adult height with cancer are less well studied. Women from the French E3N study, born between 1925 and 1950, were followed biennially from 1995 until 2008. Body shape was classed into four groups based on median WC and HC at baseline. Hazard ratios (HRs) were estimated by Cox proportional hazards regression models. Over the 12 years of follow-up, 7,247 of 63,798 women developed cancer. As WC increased, we found a trend for decreasing cancer risk in pre-menopausal women, which reversed to an increasing risk in post-menopausal women. This remained unchanged after further adjustment for HC /or height [HR: 0.72 (0.52-1.00) before menopause and 1.17 (1.04-1.31) in the 5th vs. 1st quintile of HC], and were similar after exclusion of breast cancer. We showed that large body shape decreased cancer risk before menopause and increased it after [HR: 0.87 (0.73-1.02) and 1.11 (1.04-1.17), respectively, in women with large waist and hips compared to small waist and hips]. Adult height was associated with an non-significant increase in cancer in pre-menopause and a significant cancer risk in menopause, independent of other anthropometric characteristics [5th vs. 1st quintile [HR: 1.24 (0.98-1.56) and 1.20 (1.10-1.30)], respectively as was long birth length in post-menopausal women [HR: 1.18 (1.07-1.30) compared to medium birth length]. These results suggest independent roles of height and WC on cancer risk, through different pathways.

Height, sitting height, and leg length in relation with breast cancer risk in the E3N cohort.

BACKGROUND: If height is a well-established risk factor for breast cancer, leg length and sitting height are usually considered as better candidate biomarkers of growth hormone exposure than height, respectively, in pre- and postpuberty. METHODS: Risk of breast cancer associated with quartiles of height, sitting height, and leg length were estimated in the French E3N cohort (N = 50,704, including 2,065 breast cancer cases), stratified on both menopausal and hormone receptor statuses. RESULTS: Height was associated with an increased postmenopausal breast cancer risk [HR = 1.22 (1.06-1.41) when comparing extreme categories, P(trend) = 0.002], which was exclusively driven by the association with leg length [HR = 1.21 (1.05-1.39), P(trend) = 0.013] and not sitting height [HR = 1.03 (0.89-1.18), P(trend) = 0.379]. Leg length was associated with an increased ER(+) breast cancer risk in postmenopausal [HR = 1.24 (1.06-1.46), P(trend) = 0.004], whereas sitting height was associated with a borderline decreased ER(-) premenopausal breast cancer risk [HR = 0.45 (0.20-1.01), P(trend) = 0.011]. The positive associations observed in the overall population between leg length and breast cancer risk were actually restricted to women who had a short birth length [HR = 1.82 (1.22-2.72), P(trend) = 0.022] and those with a low birth weight [HR = 1.43 (1.00-2.04), P(trend) = 0.054]. CONCLUSION: The two components of height risk are differentially associated with breast cancer risk: leg length with an increased risk of postmenopausal ER(+) tumors and sitting height with a decreased risk of premenopausal ER(-) tumors. IMPACT: Future prospective studies should no longer consider height a single risk factor for breast cancer risk.