[Rationale for early rehabilitation of patients with uterine corpus cancer]. / Obosnovanie rannei reabilitatsii bol'nykh rakom tela matki.

OBJECTIVE: To study the dynamics of hemorheologic changes and the frequency of early complications of laparoscopic radical hysterectomy in patients with uterine corpus cancer depending on conducting rehabilitation activities in the early postoperative period. MATERIAL AND METHODS: The number of patients with uterine corpus cancer equal 49 (mean age 54.8±2.2 years), divided into 2 comparable groups, was examined: experimental group - 23 patients, who received local magnetotherapy since the first day after surgery for 5-6 days, and control group - 26 patients without physiotherapy. Comparative group included 24 healthy women. The basic rheological parameters, namely blood viscosity at high and low shear rate, hematocrit, erythrocytes' aggregation and deformability, erythrocytes and platelets electrophoretic mobility, were evaluated in all patients initially, on the 1st and 5th days after surgery and in comparison group. RESULTS: There were changes in the rheological properties of the blood before surgery in patients of both groups: increase of blood viscosity, enhancement of aggregation activity of its formed elements, decrease of erythrocytes' deformability properties. The laparoscopic radical hysterectomy was accompanied by the exacerbation of these disorders. The early magnetotherapy in patients reduced hemorheological abnormalities up to the preoperative parameters (p<0.05) for 5 days, as well as reduced the incidence of early postoperative complications by 2.4 times compared to the control group. CONCLUSION: The application of local low-frequency low-intensity magnetotherapy since the first postoperative day allows to reduce the level of postoperative hemorheological abnormalities up to the level of preoperative parameters, as well as the frequency of early postoperative complications.

Incidence and prevalence of drugs used for chronic diseases in survivors of adult-onset gynaecological cancer - A nationwide cohort study.

OBJECTIVES: To evaluate both incidence and prevalence of drugs used for chronic diseases in survivors of adult-onset gynaecological cancer. DESIGN: A prospective study. SETTING: Population-based registries. POPULATION: 1.76 million women, including 17 500 women with gynaecological cancers. METHODS: Data from the Cancer Registry of Norway was linked to the Norwegian Prescription Database and other national databases. MAIN OUTCOME MEASURES: Prevalence ratios (PRs) and hazard ratios (HRs), with 95% confidence intervals (CIs), of dispensed drugs in gynaecological cancer patients (up to 15 years after diagnosis) were estimated by log-binomial and Cox regression, respectively, with cancer-free women as reference. RESULTS: For gynaecological cancer patients, the incidence of drugs used for pain control was higher than in cancer-free women, especially the first 5 years after diagnosis, and the prevalence was high at least 10 years after. The prevalence of sex hormones was high in women with gynaecological cancer at least 10 years after diagnosis (cervical and ovarian cancer PR = 23, 95% CI 18-30 and PR = 29, 95% CI 15-38, respectively), but low in cancer-free women (0.3%). Patients with uterine corpus cancer had a higher prevalence of antidiabetics before and at least 10 years after diagnosis, most pronounced in women diagnosed before age 50 (PR = 10, 95% CI 5.0-21). The prevalence of antidepressants was moderately elevated in women with gynaecological cancers. CONCLUSIONS: Gynaecological cancer survivors, particularly cervical and ovarian cancer survivors, had an increased long-term use of drugs for pain control and sex hormones. Survivors of uterine corpus cancer used antidiabetics more often, both before and after diagnosis.

Improved long-term survival of corpus cancer in Japan: A 40-year population-based analysis.

The incidence of uterine corpus cancer has been increasing globally due to increase in obesity. However, a detailed analysis of long-term epidemiological trends of corpus cancer in Japan, where obesity is relatively minimal, has not been conducted. In this retrospective, population-based study using the Osaka Cancer Registry, we analyzed 15 255 cases of corpus neoplasia registered between 1977 and 2016. We determined the age-standardized incidence, mortality, relative survival and conditional survival rates, and the treatment trends for corpus cancer over the last 40 years in Japan. The age-standardized incidence rate of corpus neoplasia increased sharply in 2000-2011 (APC = 9.9, 95% CI: 8.4-11.3), whereas the mortality rate trended to a much more modest increase (APC = 3.3, 95% CI: 2.7-3.8). Compared to 1977-2000, 10-year survival rates for post-2000 cases of localized and regional corpus cancers significantly improved (from 87.7% [95% CI: 85.8-89.4] to 94.2% [95% CI: 92.7-95.7] and from 47.5% [95% CI: 43.3-51.6] to 64.4% [95% CI: 61.0-67.6], respectively). This was largely associated with the significant increase in the percentage of localized and regional patients who received chemotherapy instead of radiation as an adjuvant therapy combined to surgery (P < .001 for both). We found that each histological type (endometrioid carcinoma, serous carcinoma, clear cell carcinoma and carcinosarcoma) has different characteristics of trend of age-standardized incidence rate, relative survival and distribution of extent of disease. In endometrioid carcinoma, the age-standardized incidence rate increased consistently after 1990, but the rate of increase was decreasing after 1997.

Efficacy and safety of nivolumab in Japanese patients with uterine cervical cancer, uterine corpus cancer, or soft tissue sarcoma: Multicenter, open-label phase 2 trial.

Nivolumab is a human monoclonal antibody against the immune checkpoint receptor programmed death-1, inhibiting binding to programmed death-ligand 1 or 2 (PD-L1 or PD-L2). This phase 2 study evaluated the efficacy and safety of nivolumab in patients with advanced/recurrent uterine cervical cancer, uterine corpus cancer, or soft tissue sarcoma (STS). Patients received nivolumab 240 mg at 2-week intervals. Primary endpoint was objective response rate; secondary endpoints included overall survival, progression-free survival, and safety. PD-L1 expression and microsatellite-instability (MSI) status were analyzed as potential efficacy biomarkers. Objective response rate was 25%, 23%, and 0% in patients with cervical cancer (n = 20), corpus cancer (n = 22), and STS (n = 21), respectively. The lower 80% confidence intervals of objective response rates in patients with cervical or corpus cancer exceeded the threshold rate (5%); the primary endpoint was met in cervical and corpus cancer, but not in STS. Median progression-free survival was 5.6, 3.4, and 1.4 months, and 6-month overall survival was 84%, 73%, and 86% in cervical cancer, corpus cancer, and STS, respectively. The objective response rate was higher in patients with cervical cancer with PD-L1-positive (n = 5/15; 33%) versus PD-L1-negative (n = 0/5; 0%) tumors. The two patients with corpus cancer classified as MSI-high responded; the six patients classified as microsatellite stable did not respond. Overall, nivolumab showed acceptable toxicity in all cohorts, with evidence of clinical activity in uterine cervical or corpus cancer, but not in STS. PD-L1 expression in cervical cancer and MSI-high in corpus cancer may predict clinical activity of nivolumab in these cancers.

Chronological Changes in the Gastric Cancer Subsite in Akita, Japan: The Trends from the Data of a Hospital-Based Registration System.

With the decreasing global trend in the Helicobacter pylori infection rate, compositional changes in the gastric cancer subsites have occurred worldwide. However, the compositional changes in Asian countries, including Japan, remain to be clarified. The aim of this study is to investigate the latest chronological changes in the gastric cancer subsite using a hospital-based registration system in Akita prefecture in Japan. From 2007-2015, subsites of gastric cancers were coded according to the International Classification of Diseases for Oncology (ICD-03). The nine-year registration period was divided into the three 3-year periods: 2007-2009, 2010-2012, and 2013-2015. A total of 10,804 cases of gastric cancer were registered. The proportion of cardiac cancer among total gastric cancer slightly but significantly declined from 12.1% in 2007-2009 to 9.2% in 2013-2015 (P < 0.01). Among non-cardia cancer, the proportion of corpus cancer significantly increased from 41.3% to 50.2% during the study period (P < 0.01), while that of antropylorus cancer significantly decreased from 37.6% to 34.3% (P < 0.05). Such compositional changes in the gastric cancer subsite were observed largely in men, regardless of the histologic subtype of cancer. With the decreasing H. pylori infection rate, compositional changes in the gastric cancer subsite are occurring in Japan. While the proportion of cardia and antropylorus cancer is declining, that of corpus cancer is increasing, indicating diverse etiology of gastric carcinogenesis depending on the subsites. Identifying the most common sites of occurrence, may help to improve the efficiency of screening for gastric cancer.

A nationwide multi-institutional retrospective study to identify prognostic factors and develop a graded prognostic assessment system for patients with brain metastases from uterine corpus and cervical cancer.

BACKGROUND: The prevalence of brain metastases (BM) from uterine cancer has recently increased because of the improvement of overall survival (OS) of patients with uterine cancer due to its early detection and improved local control as a result of new effective treatments. However, little information is available regarding their clinical characteristics and prognosis, because oncologists have encountered BM from uterine cancer on rare occasions. METHODS: Records from 81 patients with uterine BM were collected from 10 institutes in Japan. These were used in a multi-institutional study to identify prognostic factors and develop a graded prognostic assessment (GPA) for patients with BM from uterine cancer. RESULTS: Median OS after the development of BM was 7 months (95% confidence interval, 4 to 10 months). Multivariate analysis revealed that there were survival differences according to the existence of extracranial metastases and number of BM. In the present uterine-GPA, a score of 0 was assigned to those patients with ≥5 BM and extracranial metastasis, a score of 2 was assigned to those patients with one to four BM or without extracranial metastasis, and a score of 4 was assigned to those patients with one to four BM and without extracranial metastasis. The median OS for patients with a uterine-GPA scores of 0, 2, and 4 was 3, 7, and 22 months, respectively. A survival analysis confirmed the presence of statistically significant differences between these groups (p < 0.05). The results were validated by data obtained from the National Report of Brain Tumor Registry of Japan. CONCLUSION: Uterine GPA incorporates two simple clinical parameters of high prognostic significance and can be used to predict the expected survival times in patients with BM from uterine cancer. Its use may help in determining an appropriate treatment for individual patients with BM.

Comorbidity is an independent prognostic factor in women with uterine corpus cancer: a nationwide cohort study.

OBJECTIVE: To determine whether comorbidity independently affects overall survival in women with uterine corpus cancer. DESIGN: Cohort study. SETTING: Denmark. STUDY POPULATION: A total of 4244 patients registered in the Danish Gynecologic Cancer database with uterine corpus cancer from 1 January 2005 until 13 October 2011. METHODS: All patients included in the study were assigned a comorbidity score according to the Charlson Comorbidity Index. Multivariate survival analyses were performed to investigate the prognostic impact of comorbidity adjusting for known prognostic factors. As performance status might capture the prognostic impact of comorbidity and because information on the variable grade was missing in some special histological subtypes, we included different models in the multivariate analyses with and without PS and grade, respectively. MAIN OUTCOME MEASURES: Overall survival. RESULTS: Univariate survival analysis showed a significant (p < 0.001) negative association between increasing level of comorbidity and overall survival. Multivariate analyses adjusting for other prognostic factors showed that comorbidity is a significant independent prognostic factor with hazard ratios ranging from 1.27 to 1.42 in mild, 1.69 to 1.74 in moderate, and 1.72 to 2.48 in severe comorbidity. Performance status was independently associated to overall survival and was found to slightly reduce the prognostic impact of comorbidity. CONCLUSION: Comorbidity is an independent prognostic factor in uterine corpus cancer and increasing levels of comorbidity are associated with shorter survival.

Trends in gynaecologic cancer mortality and the impact of the COVID-19 pandemic in the United States.

OBJECTIVES: Our aim was to assess the trend in gynaecologic cancer (GC) mortality in the period from 2010 to 2022 in the United States, with focus on the impact of the pandemic on increased deaths. METHODS: GC mortality data were extracted from the Center for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) platform. We analysed mortality trends and evaluated observed vs. predicted mortality for the period from 2020 to 2022 with joinpoint regression and prediction modelling analyses. RESULTS: A total of 334,382 deaths among adults aged 25 years and older with gynaecologic cancer were documented from 2010 to 2022. The overall age-standardised mortality rate (ASMR, per 100,000 persons) for ovarian cancer-related death decreased gradually from 7.189 in 2010 to 5.517 in 2019, yielding an APC (annual percentage change) of -2.8%. However, the decrease in ovarian cancer-related mortality slowed down by more than 4-fold during the pandemic. Cervical cancer -related mortality decreased slightly prior to the pandemic and increased during the pandemic with an APC of 0.6%, resulting in excess mortality of 4.92%, 9.73% and 2.03% in 2020, 2021 and 2022, respectively. For uterine corpus cancer, the ASMR increased from 1.905 in 2010 to 2.787 in 2019, and increased sharply to 3.079 in 2021 and 3.211 in 2022. The ASMR rose steadily between 2013 and 2022, yielding an APC of 6.9%. CONCLUSIONS: Overall, we found that GC-related mortality increased during the COVID-19 pandemic, and this increase was not specific to age, race, or ethnicity.

Occult clear cell carcinoma arising from oxidative stress­exposed cystic adenomyosis: A case report.

Although adenomyosis is a benign uterine disease, it can turn malignant in rare instances. Cystic adenomyosis is a rare variation of adenomyosis, arising from which 8 cases of clear cell carcinoma have been reported. However, to the best of our knowledge, there have been no previous reports describing the mechanism by which clear cell carcinoma develops from cystic adenomyosis. The present report documents a case of a 73-year-old woman who was referred to Kanazawa University Hospital (Kanazawa, Japan) because of cystic adenomyosis, with a solid part inside the cyst. The patient was diagnosed with cystic adenomyosis at Shonan Obstetrics and Gynecology Hospital (Hakusan, Japan) 17 years prior; however, the size of the cyst increased after menopause. Therefore, malignant transformation was suspected, which warranted simple abdominal hysterectomy and bilateral salpingo-oophorectomy. The final diagnosis of the present case was uterine corpus cancer, clear cell carcinoma, stage IA. Immunohistochemical staining revealed that the normal and transitional atypical epithelial cells lining the cyst wall, in addition to the clear cell carcinoma cells (which were inside mural nodules located on the cyst wall), were positive for 8-hydroxy-20-deoxyguanosine. This observation suggested the presence of chronic oxidative stress around the cystic adenomyosis. Therefore, the present case suggests the possible involvement of chronic oxidative stress in the malignant transformation of cystic adenomyosis to clear cell carcinoma. This mechanism of malignant transformation of cystic adenomyosis appears to be similar to that of the malignant transformation of endometriotic cysts. Therefore, if the size of the cystic adenomyosis increases after menopause or if the solid part appears in the cyst in future cases, then the possibility of malignant transformation should be considered.

Gene Expression Analysis for Uterine Cervix and Corpus Cancer Characterization.

The analysis of gene expression quantification data is a powerful and widely used approach in cancer research. This work provides new insights into the transcriptomic changes that occur in healthy uterine tissue compared to those in cancerous tissues and explores the differences associated with uterine cancer localizations and histological subtypes. To achieve this, RNA-Seq data from the TCGA database were preprocessed and analyzed using the KnowSeq package. Firstly, a kNN model was applied to classify uterine cervix cancer, uterine corpus cancer, and healthy uterine samples. Through variable selection, a three-gene signature was identified (VWCE, CLDN15, ADCYAP1R1), achieving consistent 100% test accuracy across 20 repetitions of a 5-fold cross-validation. A supplementary similar analysis using miRNA-Seq data from the same samples identified an optimal two-gene miRNA-coding signature potentially regulating the three-gene signature previously mentioned, which attained optimal classification performance with an 82% F1-macro score. Subsequently, a kNN model was implemented for the classification of cervical cancer samples into their two main histological subtypes (adenocarcinoma and squamous cell carcinoma). A uni-gene signature (ICA1L) was identified, achieving 100% test accuracy through 20 repetitions of a 5-fold cross-validation and externally validated through the CGCI program. Finally, an examination of six cervical adenosquamous carcinoma (mixed) samples revealed a pattern where the gene expression value in the mixed class aligned closer to the histological subtype with lower expression, prompting a reconsideration of the diagnosis for these mixed samples. In summary, this study provides valuable insights into the molecular mechanisms of uterine cervix and corpus cancers. The newly identified gene signatures demonstrate robust predictive capabilities, guiding future research in cancer diagnosis and treatment methodologies.

A case of solitary lymph node recurrence 9 years after initial treatment for advanced premenopausal endometrioid endometrial cancer; clinical usefulness of hormonal replacement therapy.

There is no consensus on the use of hormone replacement therapy (HRT) after treatment of advanced corpus cancer. We report a case of advanced corpus cancer at a young age, in which HRT was initiated 7 years after surgery, and regional lymph node recurrence was later detected. The patient was 35 years old at the time of initial treatment in X year, when she was diagnosed with stageIIIC2 corpus cancer and underwent a hysterectomy with bilateral salpingo-oophorectomy and a retroperitoneal lymphadenectomy. HRT was started at X + 7 years, and at X + 9 years, a 25 × 12-mm-sized mass was found in the hilum of the right kidney. A laparoscopic resection revealed regional lymph node recurrence of the corpus cancer. A retrospective study further revealed that a tumor measuring 12 × 3 mm was found at X + 3 years and grew to 18 × 7 mm in X + 6 years, just before the start of the HRT. We hypothesize that HRT did not induce tumor recurrence; instead, it allowed for long-term follow-up and early diagnosis.

From Infection to Malignancy: Tracing the Impact of Human Papillomavirus on Uterine Endometrial Cancer in a Nationwide Population-Based Cohort Study.

Uterine endometrial cancer (EC) is the most common gynecological malignancy in Taiwan. This study aimed to investigate the association between human papillomavirus (HPV) infection and the development of uterine EC among Taiwanese women. A nationwide population cohort research approach was employed, leveraging longitudinal health insurance databases (LHID 2007 and 2015) from the National Health Insurance Research Database alongside data from the Taiwan Cancer Registry datasets. A comparative analysis examined 472,420 female patients with HPV infection and 944,840 without HPV infection. The results demonstrated that the HPV cohort exhibited a significantly elevated risk of uterine EC, as evidenced by an adjusted hazard ratio (aHR) of 1.588 (95% CI: 1.335-1.888). Furthermore, this elevated risk extended to type 1 EC with an aHR of 1.671 (95% CI: 1.376-2.029), specifically the endometrioid adenocarcinoma subtype with an aHR 1.686 (95% CI: 1.377-2.065). Importantly, these findings were statistically significant (p < 0.001). In conclusion, this research unveils a potential association between HPV infection and an increased risk of uterine EC, particularly the type 1 endometrial cancer subtype, within the Taiwanese female population. These findings have implications for preventive measures and screening programs targeting HPV infection to reduce the risk of this prevalent gynecological malignancy in Taiwan.

The Risk of Endometrial Cancer and Uterine Sarcoma Following Endometriosis or Pelvic Inflammatory Disease.

The relationship between uterine corpus cancer and endometriosis was conflicting. We aimed to determine the risk of uterine cancer in patients with endometriosis or pelvic inflammatory disease (PID). In this population-based cohort study, a total of 135,236 females with endometriosis (n = 20,510) or PID (n = 114,726), as well as 135,236 age-matched controls, were included. Cox regression models estimated the risk of uterine cancer in each group. Sub-outcomes of risk for uterine corpus cancer included endometrial cancer and uterine sarcoma were analyzed. An age subgroup analysis was performed to determine the moderator effect of age. A landmark analysis depicted the time varying effect of endometriosis and PID. A propensity score matching analysis was conducted to validate the findings. Patients with endometriosis had significantly higher risk of endometrial cancer (adjusted hazard ratio, aHR = 2.92; 95% CI = 2.12-4.03) and uterine sarcoma (aHR = 5.83; 95% CI = 2.02-16.89), while PID was not associated with the risk of uterine cancer. The increased risk of uterine cancer in patients with endometriosis persisted after propensity score matching (aHR = 2.83, 95%CI = 1.70-4.71). The greatest risk of endometrial cancer occurred in patients who had endometriosis for 37 to 60 months (adjusted relative risk, aRR = 9.15, 95% CI = 4.40-19.02). Females aged 12 to 35 years were at the greatest risk of endometriosis-associated uterine cancer (RR = 6.97, 95% CI = 3.41-14.26). In conclusion, patients with endometriosis were at great risk of uterine cancer, including endometrial cancer and uterine sarcoma, compared with propensity score-matched populations and compared with patients of PID. Younger females with endometriosis and patients who had endometriosis for three to five years were at the greatest risk of endometriosis-associated uterine cancer.

MicroRNA-21 expression in cancer cells is an independent biomarker of progression-free survival of endometrioid endometrial carcinoma.

Endometrial carcinoma is one of the most common gynecological cancers. MicroRNA-21 (miR-21) is the most consistently overexpressed miRNA in almost all human cancer types, and it might be a useful clinical biomarker and therapeutic target. However, its precise localization and significance in endometrial carcinoma have not been clarified. This study aimed to examine miR-21 expression in endometrial carcinoma and reveal its clinicopathological importance. We investigated miR-21 expression by in situ hybridization (ISH) using locked nucleic acid (LNA)-modified probes in 230 endometrial carcinoma patients. We evaluated miR-21 expression in cancer cells and stroma separately. High miR-21 expression in cancer cells was significantly associated with higher histological grade and lymph node metastasis. In Kaplan-Meier analysis, high miR-21 expression in cancer cells was significantly associated with poor progression-free survival. In particular, in endometrioid carcinoma, high miR-21 expression in cancer cells was an independent prognostic factor associated with poor progression-free survival, as well as older age and higher International Federation of Gynecology and Obstetrics (FIGO) stage.

Correlation of high LAT1 expression with the prognosis of endometrioid carcinoma of the uterine corpus.

The expression of L-type amino acid transporter 1 (LAT1) has been described to play essential roles in cancer cell growth and survival. To determine the significance of LAT1 in the prognosis of endometrial endometrioid carcinoma, we investigated LAT1 expression in 353 endometrioid carcinoma patients by immunohistochemical analysis using tissue microarray. The tumors in which stained tumor cells made up more than 25% of the tumor were graded as high expression. High expression of LAT1 was detected in 29 (8.2%) of patients. The ratio of high LAT1 expression did not significantly differ by age (< 60 vs. ≥ 60), FIGO stage (stage I/II vs. III/IV), histological grade (grade 1 vs. grade 2/3), or lymph node metastasis (positive vs. negative). However, high LAT1 expression in endometrioid carcinoma was associated with a poorer progression-free survival and overall survival, as per the results of the log-rank test (P = 0.0263 and 0.0404, respectively). Cox univariate and multivariate analyses revealed that high LAT1 expression is an independent marker of poor progression-free survival (hazard ratio = 2.598, P = 0.0137), in addition to a higher age (≥ 60 years vs. < 60 years), FIGO stage (stage III/IV vs. I/II), and histological grade (grade 2/3 vs. grade 1). In conclusion, we demonstrate that LAT1 is associated with a poor prognosis of endometrioid carcinoma of the uterine corpus.

Laparoscopic Repair of Vaginal Evisceration after Abdominal Hysterectomy for Uterine Corpus Cancer: A Case Report and Literature Review.

Vaginal cuff dehiscence is a rare but serious complication that can develop after hysterectomy. Emergent surgical intervention is required for vaginal cuff dehiscence due to the potential subsequent vaginal evisceration, which may lead to necrosis of the small bowel. A 62-year-old nulliparous woman with a 30-year history of smoking, diabetes mellitus, and rheumatoid arthritis (treated with oral steroids) presented with a vaginal cuff dehiscence. Thirty-eight days before the admission, she had undergone a radical operation including total abdominal hysterectomy for uterine corpus cancer at another hospital. We performed emergent laparoscopic surgery to reduce the prolapsed small bowel into the abdominal cavity and repaired the vaginal cuff with a two-layer continuous closure using absorbable barbed sutures. The patient experienced no postoperative complications, and no recurrence of the vaginal cuff dehiscence occurred. Vaginal cuff dehiscence and evisceration can be surgically managed using an abdominal, vaginal, or laparoscopic approach, and the choice of method should be based on patient characteristics and the surgeon's skills. Laparoscopic vaginal cuff repair with a two-layer continuous closure using absorbable barbed sutures is a minimally invasive technique that is safe and effective for medically stable patients with no small bowel injury or vascular compromise and no pelvic abscess.

An ecological study of cancer incidence and mortality rates in France with respect to latitude, an index for vitamin D production.

France has unexplained large latitudinal variations in cancer incidence and mortality rates. Studies of cancer rate variations in several other countries, as well as in multicountry studies, have explained such variations primarily in terms of gradients in solar ultraviolet-B (UVB) doses and vitamin D production. To investigate this possibility in France, I obtained data on cancer incidence and mortality rates for 21 continental regions and used this information in regression analyses with respect to latitude. This study also used dietary data. Significant positive correlations with latitude emerged for breast, colorectal, esophageal (males), lung (males), prostate, both uterine cervix and uterine corpus, all and all less lung cancer. Although correlations with latitude were similar for males and females, the regression variance for all and all less lung cancer was about twice as high for males than for females. Lung cancer incidence and mortality rates for females had little latitudinal gradient, indicating that smoking may have also contributed to the latitudinal gradients for males. On the basis of the available dietary factor, micro- and macronutrient data, dietary differences do not significantly affect geographical variation in cancer rates. These results are consistent with solar UVB's reducing the risk of cancer through production of vitamin D. In the context of serum 25-hydroxyvitamin D level-cancer incidence relations, cancer rates could be reduced significantly in France if everyone obtained an additional 1,000 IU/day of vitamin D. Many other benefits of vitamin D exist as well.