Acute Kidney Injury and Hair-Straightening Products: A Case Series.

RATIONALE & OBJECTIVE: Keratin-based hair-straightening treatment is a popular hair-styling method. The majority of keratin-based hair-straightening products in Israel contain glycolic acid derivatives, which are considered safe when used topically. Systemic absorption of these products is possible, and anecdotal reports have described kidney toxicity associated with their use. We report a series of cases of severe acute kidney injury (AKI) following use of hair-straightening treatment in Israel during the past several years. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: We retrospectively identified 26 patients from 14 medical centers in Israel who experienced severe AKI and reported prior treatment with hair-straightening products in 2019-2022. FINDINGS: The 26 patients described had a median age of 28.5 (range, 14-58) years and experienced severe AKI following a hair-straightening procedure. The most common symptoms at presentation were nausea, vomiting, and abdominal pain. Scalp rash was noted in 10 (38%) patients. Two patients experienced a recurrent episode of AKI following a repeat hair-straightening treatment. Seven patients underwent kidney biopsies, which demonstrated intratubular calcium oxalate deposition in 6 and microcalcification in tubular cells in 1. In all biopsies, signs of acute tubular injury were present, and an interstitial infiltrate was noted in 4 cases. Three patients required temporary dialysis. LIMITATIONS: Retrospective uncontrolled study, small number of kidney biopsies. CONCLUSIONS: This series describes cases of AKI with prior exposure to hair-straightening treatments. Acute oxalate nephropathy was the dominant finding on kidney biopsies, which may be related to absorption of glycolic acid derivatives and their metabolism to oxalate. This case series suggests a potential underrecognized cause of AKI in the young healthy population. Further studies are needed to confirm this association and to assess the extent of this phenomenon as well as its pathogenesis.

Persistent Asymptomatic Isolated Microscopic Hematuria in Adolescents is not Associated With an Increased Risk for Early Onset Urinary Tract Cancer.

OBJECTIVE: To elucidate the association between adolescent microscopic hematuria and early onset urothelial carcinoma and renal cell carcinoma. METHODS: Nationwide, population-based, retrospective cohort study using medical data of 970,366 adolescents aged 16 through 19 years (58.6% male) examined for fitness for military service between 1980 and 1997. Diagnoses of persistent isolated microscopic hematuria were given after thorough work up process excluding any other renal abnormalities. Incident cases of urothelial carcinoma and renal cell carcinoma diagnosed during the years of 1982-2012 were retrieved from the Israeli National Cancer Registry. Cox proportional hazards models were used to estimate the hazard ratio (HR) separately for urothelial carcinoma and renal cell carcinoma. RESULTS: During a cumulative follow-up of 22,115,629 person-years (median follow-up, 22.8), persistent isolated microscopic hematuria was diagnosed among 5509 (0.6%) adolescents. Urothelial carcinoma and renal cell carcinoma developed in 332 (3 among those with persistent isolated microscopic hematuria) and 292 (2) individuals, respectively. The adjusted HR for incident urothelial carcinoma among adolescents with isolated microscopic hematuria was 1.17 (95% CI, 0.38-3.66) and the adjusted HR for renal cell carcinoma was 1.02 (95% CI, 0.25-4.12). CONCLUSION: Persistent asymptomatic isolated microscopic hematuria at adolescence was not associated with increased risk for urothelial carcinoma nor renal cell carcinoma.

The Relationship between Hypertension and Cancer.

BACKGROUND: Hypertension and cancer are both common due to the aging of the population and the advances in medical treatment which result in increased survival of cancer patients today. More patients with cancer; therefore, present with hypertension, which is attributed to different factors, including genetics and age as well as the type of tumor and cancer-related treatments. Given the increased cardiovascular and mortality risk related to hypertension, it is important to appropriately identify and treat hypertension, particularly in the population of vulnerable cancer patients. In this article we discuss the epidemiology, different etiologies, and approaches to the management of hypertension in cancer patients.

Adolescent overweight and obesity and the risk for pancreatic cancer among men and women: a nationwide study of 1.79 million Israeli adolescents.

BACKGROUND: There is growing concern regarding the impact of adolescent obesity on adult health. The objective of this study was to evaluate the association between body mass index (BMI) in late adolescence and the incidence of pancreatic cancer during adulthood. METHODS: The authors analyzed a cohort of 1087,358 Israeli Jewish men and 707,212 Jewish women who underwent a compulsory physical examination between ages 16 and 19 years from 1967 to 2002. Pancreatic cancer incidence through December 31, 2012 was identified by linkage to the national cancer registry. Multivariable-adjusted Cox regression was used to estimate hazard ratios (HRs) for pancreatic cancer according to the US Centers for Disease Control and Prevention (CDC) BMI percentiles at baseline. RESULTS: Over a median 23 year follow-up, 551 incident cases of pancreatic cancer cases occurred (423 men; 128 women). Compared with normal weight (5th to-<85th percentile), obesity (≥95th percentile) was associated with an increased risk of cancer among both men (HR, 3.67; 95% confidence interval [CI], 2.52-5.34) and women (HR, 4.07; 95% CI, 1.78-9.29). Among men, compared with low-normal BMI (≥5th to <25th percentile), high-normal BMI (≥75th to <85th percentile) and overweight (85th to 95th percentile) also were associated with a higher risk for cancer(high-normal BMI: HR, 1.49; 95% CI, 1.05-2.13; overweight: HR, 1.97; 95% CI, 1.39-2.80). The estimated population-attributable fraction because of overweight and obesity was 10.9% (95% CI, 6.1%-15.6%). CONCLUSIONS: Men and women who were obese or overweight as adolescents are at an increased risk for subsequent pancreatic cancer.

Risk factors associated with gastroenteropancreatic neuroendocrine tumors in a cohort of 2.3 million Israeli adolescents.

We investigated whether obesity and sociodemographic factors at adolescence are associated with incident gastroenteropancreatic neuroendocrine tumors (GEP-NET).Our cohort included 2.3 million Israeli adolescents examined at ages 16 to 19 years between 1967 and 2010. The baseline database included sex, country of birth, residential socioeconomic status (SES), body-mass index (BMI) and height. Participants were followed through linkage with the National Cancer Registry up to 2012. We identified 221 cases of GEP-NET (66 pancreatic, 52 gastric, 39 rectal, 27 appendiceal, 23 small bowel and 14 colonic). Immigration from the Former Soviet Union (FSU) was associated with the risk of small bowel and rectal NET's, [Hazard Ratio (HR) 4.79, 95% Confidence Interval (CI) 1.37-16.76 and 3.43, 95% CI 1.20-9.83, respectively].Height >75th percentile and BMI ≥ 85th percentile were associated with increased risk of gastric NET (HR 2.25 95% CI 1.14-4.42 and HR 2.38, 95% CI 1.19-4.75, respectively). Female sex was associated with appendiceal NET (HR 2.30, 95% CI 1.06-4.96) while male gender was associated with an increased risk for NET of the small bowel [HR 4.72 (95% CI 1.10-20.41)].In conclusion, our findings suggest different risk factor associations with the various GEP-NETS: immigrants from the FSU were at increased risk for small bowel and rectal NET; increased height and weight were associated with the risk of gastric NET and females were at increased risk for appendiceal NET. Further focus on the FSU population is indicated in addition to studies verifying the association of BMI and height with gastric NET.

Body mass index at adolescence and risk of noncardia gastric cancer in a cohort of 1.79 million men and women.

BACKGROUND: This study assessed adolescent predictors of noncardia gastric cancer (NCGC) with a focus on the body mass index (BMI) in late adolescence. METHODS: This study analyzed a cohort of 1,087,358 Israeli Jewish males and 707,212 Israeli Jewish females who underwent a compulsory physical examination between the ages of 16 and 19 years from 1967 to 2002. By linkage to the national cancer registry, participants were followed for NCGC through December 31, 2012. With a median follow-up of 23 years, 515 NCGC cases occurred (379 men and 136 women), and the median age was 47.0 years (interquartile range, 39.3-53.4 years). Multivariate-adjusted Cox regression was used to estimate hazard ratios (HRs) for NCGC according to the US Centers for Disease Control and Prevention BMI percentiles at the baseline (normal weight, 5th to <85th percentile; overweight, 85th to <95th percentile; and obesity, ≥95th percentile) as well as the country of birth, residential socioeconomic status (SES), and education. RESULTS: In comparison with normal weight, adolescent obesity, but not overweight, was associated in both men and women with the risk of subsequent NCGC (unadjusted HR, 1.95; 95% confidence interval [CI], 1.25-3.06; adjusted HR, 1.78; 95% CI, 1.12-2.83). Immigration from the former Soviet Union (FSU), a low education level, and a low residential SES were also associated with the risk for NCGC with adjusted HRs of 2.67 (95% CI, 1.86-3.83), 1.85 (95% CI, 1.53-2.25), and 1.48 (95% CI, 1.13-1.93), respectively. CONCLUSIONS: The findings suggest that adolescent obesity, but not overweight, is associated with an increased risk for NCGC. Immigration from the FSU, a low residential SES, and a low education level are also significantly associated with the risk for NCGC. Cancer 2018;124:356-63. © 2017 American Cancer Society.

Adolescent obesity and adult male breast cancer in a cohort of 1,382,093 men.

Male breast cancer (MBC) accounts for 1% of all breast cancer. Adult obesity and tallness are risk factors for MBC, but the role of adolescent fatness is largely unknown. We aimed to assess the association between body mass index (BMI) in adolescence and the incidence of MBC in a large cohort of 16- to 19-year-old Israeli males. 1,382,093 Jewish Israeli males aged 16-19 who underwent anthropometric measurements, a general intelligence test (GIT) and other examinations during 1967-2011, were followed up to December 31, 2012 for MBC incidence. Cox proportional hazards models assessed the association between adolescent BMI (as WHO BMI categories and as age-specific CDC percentiles) and time to MBC diagnosis, adjusting for sociodemographic covariates. Of 100 MBC cases diagnosed during 29,386,233 person-years of follow-up, 97 were included in multivariable analyses. Compared to "healthy" BMI (18.5-24.9 kg/m2 ) and adjusted for year of birth, country of origin and GIT score, higher adolescent BMI was associated with higher MBC risk: hazard ratio (HR) = 2.01 (95% confidence interval [CI] 1.14-3.55, p = 0.015) in overweight (25.0 ≤ BMI < 30.0 kg/m2 ) adolescents; and HR = 4.97 (95%CI 2.14-11.53, p = 0.0002) in obese (BMI ≥ 30.0 kg/m2 ) adolescents. When CDC age-specific BMI percentiles were assessed results were similar and statistically significant for obesity. In addition, low (vs. high) GIT score (HR = 4.76, 95%CI 1.96-12.50, p = 0.001) and European (vs. west-Asian) origin (HR = 1.99, 95%CI 1.19-3.34, p = 0.009) were independent predictors of MBC. Measured adolescent overweight and obesity are associated with increased risk of MBC, suggesting a modifiable risk factor potentially allowing for early intervention. The novel association with cognitive function should be further explored.

Adolescent body mass index and risk of colon and rectal cancer in a cohort of 1.79 million Israeli men and women: A population-based study.

BACKGROUND: This study examined the association between the body mass index (BMI) in late adolescence and the risk of colon and rectal cancer. METHODS: This study analyzed a cohort of 1,087,358 Jewish men and 707,212 Jewish women who underwent health examinations at the ages of 16 to 19 years between 1967 and 2002 and were followed by linkage to the national cancer registry up to 2012. Cox regression was used to estimate hazard ratios (HRs) for cancer according to age- and sex-adjusted BMI percentiles from the US Centers for Disease Control and Prevention (overweight, 85th percentile to <95th percentile; obesity, ≥95th percentile). RESULTS: Over a median follow-up of 23 years, 2967 incidence cases of colorectal cancer, including 1977 among men (1403 in the colon and 574 in the rectum) and 990 among women (764 in the colon and 226 in the rectum), were identified. Overweight and obesity were associated with the risk for colon cancer among both men (HR for overweight, 1.53; 95% confidence interval [CI], 1.28-1.84; HR for obesity, 1.54; 95% CI, 1.15-2.06; statistically significant from a BMI of 23.4 kg/m2 [spline analysis]) and women (HR for overweight, 1.54; 95% CI, 1.22-1.93; HR for obesity, 1.51; 95% CI, 0.89-2.57; significant from a BMI of 23.6 kg/m2 ). Obesity, but not overweight, was associated with a risk for rectal cancer among men (HR, 1.71; 95% CI, 1.11-2.65; significant from a BMI of 29.6 kg/m2 ) and women (HR, 2.03; 95% CI, 0.90-4.58; significant from a BMI of 30.6 kg/m2 ). CONCLUSIONS: Being overweight or obese in adolescence was associated with an increased risk of subsequent colon cancers in men and women, whereas obesity was associated with rectal cancer. Cancer 2017;123:4022-30. © 2017 American Cancer Society.

Obesity and related risk of myeloproliferative neoplasms among israeli adolescents.

OBJECTIVE: Obesity has been associated with various malignancies, but a clear association between overweight and myeloproliferative neoplasms (MPN) has not been established. METHODS: This study assessed the association between adolescent obesity and future risk for MPN. Data on 2,516,256 Israeli adolescents, who underwent a compulsory general health examination at ages 16 to 19, between 1967 and 2011, were linked to the National Cancer Registry in this nationwide, population-based cohort study. Cox proportional hazards models were used to estimate the hazard ratio (HR) for MPN associated with BMI measured at adolescence. RESULTS: The mean follow-up of 19.86 ± 12.15 years reflected 49,977,521 person years, during which 433 examinees developed MPN, primarily chronic myelogenous leukemia, polycythemia vera, and essential thrombocythemia. Obesity (BMI ≥ 95th percentile) in adolescence significantly predicted increased risk of MPN with HR (adjusted for sex) of 1.81 (95% confidence interval 1.13-2.92, P = 0.014). CONCLUSIONS: Adolescent obesity might be related to an increased incidence of myeloproliferative neoplasms.

Risk of Hodgkin lymphoma according to immigration status and origin: a migrant cohort study of 2.3 million Jewish Israelis.

Hodgkin Lymphoma (HL), a common early adulthood malignancy, has a complex etiology. We conducted a migrant cohort study to assess immigration status and origin as predictors of HL in Israel, which has among the highest rates of HL worldwide. Nationwide data on 2,285,009 16-19-year-old Jewish adolescents, collected from 1967-2011, were linked to Israel's Cancer Registry to obtain the incidence of HL until 2012. Two thousand and ninety-three HL cases were detected during 47.0 million person-years of follow-up. Using multivariable-adjusted Cox proportional hazards modeling, risk was higher for Israeli-born compared to immigrants, similarly across origin groups (HR = 1.59; 95%CI 1.32-1.92 for the dominant nodular sclerosis subtype). Risk of HL was greater for more recent year of birth, higher BMI, taller stature, and apparently for women. These findings suggest that exposure to as yet unidentified elements of the Israeli environment increase the risk of nodular sclerosis HL, and should aid in directing research efforts.

Risk of nasopharyngeal carcinoma penetrates across immigrant generations: A migrant cohort study of 2.3 million Jewish Israeli adolescents.

Nasopharyngeal cancer (NPC) incidence varies widely across geographic regions and ethnic groups. We conducted a large-scale migrant cohort study to assess origin and migrant generation as predictors of NPC, controlling for possible confounders. Data on 2.3 million Jewish Israeli adolescents, who underwent a compulsory general health examination at ages 16-19 between the years 1967 and 2011 were linked to the Israel National Cancer Registry to obtain incident NPC up to 2012. Cox proportional hazards were used to model time to event. During 46.5 million person-years of follow-up, 276 incident cases were identified. Origin was a strong independent predictor of NPC with high rates for first generation North African born (adjusted HR 5.52; 95% CI 2.43-12.52; p < 0.000044) and Asian born (adjusted HR 3.79; 95% CI 1.43-10.00; p = 0.007) compared to European-born, adjusted for sex, year of birth, residential socio-economic position, years of education, rural residence, body mass index and height. The magnitude of the associations was similar in the Israeli-born of North African and Asian origin, with these second and third generation immigrants showing elevated HRs (adjusted HR 6.09; 95% CI 2.81-13.20; p = 4.72.10-6 and 3.86; 95% CI 1.77-8.41; p = 0.00067, respectively). These findings suggest a strong genetic predisposition and/or efficient cultural transmission of environmental exposures in the etiology of NPC.

The novel compound STK405759 is a microtubule-targeting agent with potent and selective cytotoxicity against multiple myeloma in vitro and in vivo.

Despite advances in treatment, multiple myeloma (MM) remains incurable. Here we propose the use of STK405759, a novel microtubule targeting agent (MTA) and member of the furan metotica family for MM therapy.STK405759 inhibited tubulin polymerization in a cell-free system and in myeloma cells. This molecule had potent cytotoxic activity against several MM cell lines and patient-derived MM cells. Moreover, STK405759 demonstrated cytotoxicity against drug-resistant myeloma cells that overexpressed the P-glycoprotein drug-efflux pump. STK405759 was not cytotoxic to peripheral blood mononuclear cells, including activated B and T lymphocytes. This compound caused mitotic arrest and apoptosis of myeloma cells characterized by cleavage of poly (ADP-ribose) polymerase-1 and caspase-8, as well as decreased protein expression of mcl-1. The combination of STK405759 with bortezomib, lenalidomide or dexamethasone had synergistic cytotoxic activity. In in vivo studies, STK405759-treated mice had significantly decreased MM tumor burden and prolonged survival compared to vehicle treated- mice.These results provide a rationale for further evaluation of STK405759 as monotherapy or part of combination therapy for treating patients with MM.

High Normal Uric Acid Levels Are Associated with an Increased Risk of Diabetes in Lean, Normoglycemic Healthy Women.

CONTEXT: The risk associated with serum uric acid (SUA) levels within the normal range is unknown, especially among lean and apparently healthy adults. OBJECTIVE: Evaluating whether high-normal SUA levels, 6.8 mg/dL and below, are associated with an increased diabetes risk, compared with low-normal SUA. DESIGN AND SETTING: This was a cohort study with 10 years of followup involving all clinics of the largest nationally distributed Health Maintenance Organization in Israel. PARTICIPANTS: Participants included 469,947 examinees, 40-70 years old at baseline, who had their SUA measured during 2002. We excluded examinees who had hyperuricemia (SUA > 6.8 mg/dL), impaired fasting glucose, overweight or obesity and chronic cardiovascular or renal disorders. The final cohort was composed of 30 302 participants. INTERVENTIONS: Participants were followed up to a new diagnosis of diabetes during the study period. MAIN OUTCOME MEASURES: Odds ratio of developing diabetes among participants with high-normal baseline SUA were compared with low-normal (2 ≤ uric acid < 3 and 3 ≤ uric acid < 4 in women and men, respectively). RESULTS: In a logistic regression model adjusted for age, body mass index, socioeconomic status, smoking, baseline estimated glomerular filtration rate, and baseline glucose, SUA levels of 4-5 mg/dL for women were associated with 61% increased risk for incident diabetes (95% confidence interval, 1.1-2.3). At the highest normal levels for women (SUA, 5-6 mg/dL) the odds ratio was 2.7 (1.8-4.0), whereas men had comparable diabetes risk at values of 6-6.8 mg/dL (hazard ratio, 1.35; 95% confidence interval, 0.9-2.1). CONCLUSIONS: SUA levels within the normal range are associated with an increased risk for new-onset diabetes among healthy lean women when compared with those with low-normal values.

Adolescent weight and height are predictors of specific non-Hodgkin lymphoma subtypes among a cohort of 2,352,988 individuals aged 16 to 19 years.

BACKGROUND: The age-adjusted annual incidence of non-Hodgkin lymphoma (NHL) has risen worldwide. This trend may be affected by the secular increase in height and the sharp upswing in adolescent overweight; these drive increased insulinlike growth factor 1 and chronic inflammation, which may play an etiologic role. This study examined the association of the body mass index (BMI) and height of adolescents with NHL subtypes, which have been insufficiently evaluated. METHODS: Health-related data on 2,352,988 Israeli adolescents, aged 16 to 19 years, who were examined between 1967 and 2011 were linked to the Israel National Cancer Registry to derive the NHL incidence up to December 31, 2012 (4021 cases). Cox proportional hazards modeling was used to estimate the multivariate-adjusted hazard ratio (HR) for NHL subtypes associated with the BMI and height of adolescents. RESULTS: Adolescent overweight and obesity were associated with an HR of 1.25 (95% confidence interval [CI], 1.13-1.37; P = 1.14 × 10(-5) ) for NHL in comparison with normal weight. There was a graded association of height with NHL (P = 4.29 × 10(-9) ), with the tallest adolescents (≥ 95th percentile vs 25th to < 50th percentiles [US Centers for Disease Control and Prevention]) exhibiting an HR of 1.28 (95% CI, 1.04-1.56). Marginal zone lymphoma, primary cutaneous lymphoma (PCL), and diffuse large B-cell lymphoma (DLBCL) showed the strongest associations for overweight/obesity, and DLBCL and PCL showed the strongest associations for height. CONCLUSIONS: The findings of this large cohort study add to the growing body of evidence showing that higher body weight and taller stature during adolescence are associated with an increased risk of NHL and may modestly contribute to its increasing incidence. Further studies are needed to elucidate the mechanisms linking anthropometric measures and NHL risk.

Israeli-born offspring of Jewish immigrants of Middle Eastern origin have a lower incidence of multiple myeloma than those of European origin: a cohort study of 746 200 Israeli men followed from late adolescence.

Differences in the prevalence of multiple myeloma across races have been observed, with a two- to three-fold greater prevalence in African Americans compared with Caucasians. Little is known about the incidence or prevalence of multiple myeloma in other populations. The association between father's country of origin and the incidence of multiple myeloma was examined in a nationwide population-based cohort. Health-related data on 746 200 16-19-year-old Jewish males examined between 1967 and 1998 were linked to the Israel National Cancer Registry to derive multiple myeloma incidence up to 2006. During 17 352 349 person-years of follow-up, 109 examinees developed plasma cell dyscrasias. Middle Eastern origin was protective compared to European origin (hazard ratio [HR] 0.39; 95% confidence interval [CI] 0.22-0.68; p = 0.001, adjusted for year of birth), and also when restricted to Israeli-born males (HR 0.44; 95% CI 0.24-0.82; p = 0.01). In conclusion, second-generation adolescents of Middle Eastern origin are at persistently lower risk of developing multiple myeloma compared to those of European origin, supporting a genetic component in the pathogenesis of multiple myeloma.

Hypertension in adolescence is not an independent risk factor for renal cancer: a cohort study of 918,965 males.

BACKGROUND: Hypertension has been repeatedly linked to renal cell cancer, independent of overweight and anti-hypertensive drug use, but its role remains unclear, especially within the growing group of relatively young-middle aged renal cancer patients. In order to delineate the role of hypertension in early onset renal cancer, we examined the association of blood pressure measured at age 17 with the incidence of renal cancer. METHODS: Sociodemographic and medical data of 918,965 adolescent males examined for fitness for military service from 1967 to 2005 were linked to the National Cancer Registry in this nationwide population-based cohort study (12,910,585 person years) to obtain cancer incidence. A single measurement of blood pressure at age 17 was stratified as optimal (<120/80), normal (≥ 120/80 < 130/85), high normal (≥ 130/85 < 140/90), or high (≥ 140/90). We used Cox proportional hazards modeling to estimate the hazard ratio of the blood pressure categories for renal cancer, adjusted for year of birth, body mass index, origin of parents, and height. We also assessed the role of a clinical diagnosis of persistent hypertension (n = 4223, based on multiple measurements). RESULTS: Of those who had their blood pressure recorded, 90 examinees developed renal cancer. In a multivariable model, the higher categories of blood pressure were associated with a decreased risk of renal cancer (hazard ratio, 0.32; 95% confidence interval, 0.12-0.84; P = .021 for blood pressure ≥ 140/90 vs < 120/80). Furthermore, there was no evidence of increased risk for those with an established diagnosis of hypertension (hazard ratio, 1.28; 95% confidence interval, 0.17-9.50; P = .81). CONCLUSIONS: It is unlikely that hypertension in adolescents carries an increased risk for renal cancer.

Adolescent obesity and paternal country of origin predict renal cell carcinoma: a cohort study of 1.1 million 16 to 19-year-old males.

PURPOSE: The incidence of renal cell carcinoma has increased in recent decades, particularly among middle-aged adults. Early precursors of renal cancer remain unclear. We evaluated the association of body mass index and height determined in late adolescence, and paternal or grandpaternal country of origin with the risk of renal cell carcinoma. MATERIALS AND METHODS: Health related data on 1,110,835 males at ages 16 to 19 years who were examined for fitness for military service between 1967 and 2005 were linked to the Israel National Cancer Registry in this nationwide, population based cohort study. We used Cox proportional hazards modeling to estimate the HR of renal cell carcinoma associated with birth year, body mass index, height, father country of origin and socioeconomic indicators. RESULTS: During 19,576,635 person-years of followup renal cancer developed in 274 examinees. Substantial excess risk was conferred by a body mass index of greater than 27.5 kg/m(2) compared to less than 22.5 kg/m(2) (HR 2.43, 95% CI 1.54-3.83, p <0.0001). Asian or African origin was protective compared to European origin (African origin HR 0.67, 95% CI 0.49-0.92). CONCLUSIONS: Overweight in late adolescence is a substantial risk factor for renal cell carcinoma. European origin is independently associated with excess risk and it persists among Israeli born males. Preventing childhood obesity may be a promising target for decreasing the burden of renal cancer.