Of the various genetic alterations in lung cancer, the abnormalities of the TP53 gene (p53) are among the most frequent and important events. Because of its importance, many aspects of TP53 have been studied, including preneoplastic lesions and TP53as a marker for early detection and prognosis and as a therapeutic option. We summarize recent knowledge of TP53 in lung cancer with a special emphasis on the relationship between smoking exposure (e.g, cigarette, etc.) and specific mutational pattern of TP53by analyzing the latest version of the International Agency for Research on Cancer (IARC) database on TP53 mutations in human cancer. Our analysis confirmed several other studies showing significant differences in the frequencies of G:C to T:A transversions between ever‐smokers and never‐smokers. Furthermore, when comparing the mutational spectrum by gender, important differences were noted between male and female never‐smokers. We concluded that the previously noted G:C to T:A transversions were mainly due to female smokers having a high frequency of these changes compared to female never‐smokers. There was no relationship between adenocarcinomas and squamous cell carcinomas independent of gender. We also examined the seven codons which have been previously identified as hot spots, that is, the sites of frequent G:C to T:A transversions in smoking‐related lung cancers. However, there was no specific codon which was strongly related to smoke exposure despite a moderate relationship. We considered the term “warmspot” may be more appropriate. While mutations of TP53 are frequent in lung cancers, further investigation is necessary to understand their role for lung carcinogenesis, especially as they relate to gender differences, and to translate our laboratory knowledge to clinical applications. Hum Mutat 21:229–239, 2003.

Background: After the Great East Japan Earthquake and Tsunami in March 2011, radioactive elements were released from the Fukushima Daiichi Nuclear Power Plant. Based on prior knowledge, concern emerged about whether an increased incidence of thyroid cancer among exposed residents would occur as a result. Methods: After the release, Fukushima Prefecture performed ultrasound thyroid screening on all residents ages ≤18 years. The first round of screening included 298,577 examinees, and a second round began in April 2014. We analyzed the prefecture results from the first and second round up to December 31, 2014, in comparison with the Japanese annual incidence and the incidence within a reference area in Fukushima Prefecture. Results: The highest incidence rate ratio, using a latency period of 4 years, was observed in the central middle district of the prefecture compared with the Japanese annual incidence (incidence rate ratio = 50; 95% confidence interval [CI] = 25, 90). The prevalence of thyroid cancer was 605 per million examinees (95% CI = 302, 1,082) and the prevalence odds ratio compared with the reference district in Fukushima Prefecture was 2.6 (95% CI = 0.99, 7.0). In the second screening round, even under the assumption that the rest of examinees were disease free, an incidence rate ratio of 12 has already been observed (95% CI = 5.1, 23). Conclusions: An excess of thyroid cancer has been detected by ultrasound among children and adolescents in Fukushima Prefecture within 4 years of the release, and is unlikely to be explained by a screening surge.

Background: It is well known that large-scale poisonings caused by methylmercury occurred in Japan (Minamata, in the 1950s) and Iraq. However, in contrast to Iraq, there have been few sound epidemiologic studies in Minamata. We evaluated the effect of methylmercury on neurologic signs using data from a 1971 population-based study. Methods: Villages in 3 areas were selected for study: the Minamata area (a high-exposure area), the Goshonoura area (a medium-exposure area), and the Ariake area (a low-exposure area). We used place of residence as the exposure indicator. We examined associations between methylmercury exposure and the following neurologic signs measured on clinical examination: paresthesia of whole body, paresthesia of extremities, paresthesia around the mouth, ataxia, dysarthria, tremors, and pathologic reflexes. Results: Total population was 1120 in the high-exposure villages, 1845 in the medium-exposure villages, and 1165 in the low-exposure villages. In the Minamata area, 87% (n=833) of the eligible population (age 10 years and older) participated in the 1971 investigations, in the Goshonoura area, 93% (n = 1450), and in the Ariake area, 77% (n = 755). Compared with subjects in the Ariake area, the subjects in the Minamata area manifested neurologic signs more frequently. The highest prevalence odds ratio was observed for paresthesia around the mouth (110; 95% confidence interval = 16–820). Although residents in the Goshonoura area had been exposed less heavily than those in the Minamata area, Goshonoura residents also had increased prevalence of neurologic signs. Conclusion: Long-term exposure to methylmercury has a strong adverse impact on neurologic signs among residents in a local community.

Objectives Long-term exposure to inorganic arsenic is related to increased risk of cancer in the lung, skin, bladder, and, possibly, other sites. However, little is known about the consequences of developmental exposures in regard to cancer risk. During early summer in 1955, mass arsenic poisoning of infants occurred in the western part of Japan because of contaminated milk powder. Okayama Prefecture was most severely affected. We examined whether the affected birth cohorts in this prefecture experienced increased cancer mortality. Methods We targeted subjects who were born from September 1950 to August 1960 and died in Okayama Prefecture between January 1969 and March 2008 due to malignant neoplasm (N = 3,141). We then compared cancer mortality (total, liver, pancreatic, lung, bladder/kidney, and hematopoietic cancers) between cohorts born before the milk poisoning (exposed group) and cohorts born after the poisoning (nonexposed group). We estimated mortality ratios and 95% confidence intervals. Results Total and liver cancers were elevated in the cohort up to 1 year of age at time of the poisoning. In addition, pancreatic and hematopoietic cancers were elevated in the cohorts up to 5 years of age, and mortality ratios were approximately twice those of the nonexposed group. Increased risk of lung and bladder/kidney cancers was not apparent. Conclusions Although dilution is present in these cohort-based data, our study highlights the notion that developmental arsenic exposure may lead to a different pattern of cancer, including increases in pancreatic and hematopoietic cancer, as compared with adult or lifetime exposures to inorganic arsenic.

Oseltamivir is a neuraminidase inhibitor that inhibits influenza virus proliferation, and is used as an antiviral drug against influenza A and B viruses. Recently, concerns have been raised about hallucinations, delirium, and abnormal activity after administration of oseltamivir for treatment of infection with influenza virus. A large epidemiologic study was conducted in Japan in the winter of 2006-2007 to assess the relationship between oseltamivir intake and adverse behaviors, and an interim report was released on 10 July 2008. In the report, the research group concluded that no positive associations were detected between oseltamivir intake and abnormal behaviors. However, the analytic method used in the study was flawed. A correct analysis (based on person-time) shows a rate ratio of 1.57 (95% confidence interval = 1.34-1.83). This example clearly illustrates the importance of person-time in the analysis of cohort studies.

Background/Objectives: Obesity is a risk factor for chronic kidney disease (CKD) in Asians. The Asia-Pacific body mass index (BMI) classification sets lower obesity cutoffs than the conventional BMI classification for all races, generally reflecting the lower BMIs in Asians. This longitudinal study evaluated the association between BMI, as classified by the Asia-Pacific BMI system, and CKD development in non-diabetic Asian adults. Methods: A population-based longitudinal study (1998–2023) was conducted in non-diabetic Japanese adults (hemoglobin A1c < 6.5%) in Zentsuji City (Kagawa Prefecture, Japan). The generalized gamma model was used to assess the relationship between time-varying BMI categories and CKD development, stratified by sex. CKD was defined as an estimated glomerular filtration rate of <60 mL/min/1.73 m². BMI was calculated as weight (kg) divided by the square of height (m²) and categorized per the Asia-Pacific classification as overweight (23.0–24.9 kg/m²), obesity class I (25.0–29.9 kg/m²), and obesity class II (≥30.0 kg/m²). Results: CKD developed in 34.2% of 3098 men and 34.8% of 4391 women. The mean follow-up times were 7.41 years for men and 8.25 years for women. During follow-up, the BMI distributions for men were 5.0% underweight, 43.3% normal weight, 25.6% overweight, 24.1% obesity class I, and 2.0% obesity class II; those for women were 7.7%, 50.5%, 20.5%, 18.3%, and 2.9%, respectively. Compared with normal weight, obesity class I was associated with a 6% (95% confidence interval [CI]: 2–10%) shorter time to CKD onset in men and 5% (95% CI: 2–7%) in women. In both sexes, obesity class II showed shorter survival times than normal weight by point estimates, although all 95% CIs crossed the null value. Conclusions: Obesity, as classified by the Asia-Pacific BMI system, shortened the time to CKD onset in non-diabetic Asians. The conventional BMI cutoff for obesity (≥30.0 kg/m²) may be too high to identify CKD risk in this population. The findings of this study may be useful for public health professionals in designing interventions to prevent CKD.