A Century of Change: Unraveling the Impact of Socioeconomic/Historical Milestones on Age at Menarche and Other Female Reproductive Factors in Japan.

BACKGROUND: Reproductive factors such as age at menarche are known to be associated with disease risk, but data on trends in these factors in Japan are limited. In this study, we investigated secular trends in reproductive factors and explored their potential association with socioeconomic and historical events. METHODS: We conducted a retrospective analysis of 62,005 Japanese women born between 1890 and 1991 using a survey conducted over 25 years. Trends in reproductive factors were analyzed using linear and joinpoint regression models, and their associations with major historical events involving Japan were evaluated. RESULTS: We found that the age at menarche showed a significant downward trend (P-value<0.001) over the century. Three joinpoints were identified, in 1932 (15.23 years old), 1946 (13.48 years old), and 1959 (12.71 years old), which indicated that average age at menarche decreased by approximately 0.8% per year between 1932 and 1946, and then by 0.4% per year between 1946 and 1959, both of which were statistically significant. However, after 1959, age of menarche remained stable. Analyses of other reproductive factors found significant changes, including a decrease in parity and the number of babies breastfed, and an increase in age at first birth. CONCLUSION: Age at menarche showed a long-term downward trend in Japan, with significant change points in annual percent change. Other factors showed secular changes in trends as well. These change points were observed at the same time as historical events, namely wars and economic development, suggesting that socioeconomic and environmental changes at the population level affect reproductive factors in females.

Cigarette smoking and pancreatic cancer risk: a revisit with an assessment of the nicotine dependence phenotype.

BACKGROUND: Cigarette smoking is a well-established risk factor of pancreatic cancer (PC). Although an association between nicotine dependence phenotype, namely time to first cigarette (TTFC) after waking, and the risk of several smoking-related cancers has been reported, an association between TTFC and PC risk has not been reported. We assessed the impact of smoking behavior, particularly TTFC, on PC risk in a Japanese population. MATERIALS AND METHODS: We conducted a case-control study using 341 PC and 1,705 non-cancer patients who visited Aichi Cancer Center in Nagoya, Japan. Exposure to risk factors, including smoking behavior, was assessed from the results of a self-administered questionnaire. The impact of smoking on PC risk was assessed with multivariate logistic regression analysis adjusted for potential confounders to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Cigarettes per day (CPD) and/or smoking duration were significantly associated with PC risk, consistent with previous studies. For TTFC and PC risk, we found only a suggestive association: compared with a TTFC of more than 60 minutes, ORs were 1.15 (95%CI, 0.65- 2.04) for a TTFC of 30-60 minutes and 1.35 (95%CI, 0.85-2.15) for that of 0-30 minutes (p trend=0.139). After adjustment for CPD or smoking duration, no association was observed between TTFC and PC. CONCLUSIONS: In this study, we found no statistically significant association between TTFC and PC risk. Further studies concerning TTFC and PC risk are warranted.

Risk factors differ for non-small-cell lung cancers with and without EGFR mutation: assessment of smoking and sex by a case-control study in Japanese.

The present study aimed to assess the impact of smoking and sex for the risk of non-small-cell lung cancer (NSCLC) with or without epidermal growth factor receptor (EGFR) mutation. We conducted a case-control study using 152 patients with EGFR-mutated (EGFRmut) NSCLC, 283 with EGFR-wild-type (EGFRwt) NSCLC and 2175 age- and sex-frequency-matched controls. Smoking was a significant risk factor for EGFRwt NSCLC (odds ratio [OR] for ever-smokers, 4.05; 95% confidence interval [CI], 2.79-5.88) but not for EGFRmut NSCLC (OR, 0.73; CI, 0.46-1.14). Sex did not affect this association. The association was observed consistently with other smoking-related parameters including pack-years. Sex was the sole risk factor for EGFRmut NSCLC (OR for women relative to men, 2.19; CI, 1.41-3.39) and there was no significant interaction between women and smoking. In contrast, sex, smoking and their interaction were significant in EGFRwt NSCLC. The impact of sex on EGFR mutation status was assessed by several indicators of reproductive history among women. Total fertile years showed a significant positive association with EGFRmut NSCLC but not with EGFRwt NSCLC. Other indicators showed similar trends and this result may partly explain the sexual difference in the acquisition of EGFR mutation. In conclusion, our case-control study clearly demonstrated that the impacts of smoking and sex on the risk of EGFRmut NSCLC are different from those for EGFRwt NSCLC. Further epidemiological evaluation is warranted.