Evidence is accumulating regarding a role of micronutrients in folate metabolism in cancer risk. We investigated the associations of plasma folate, vitamin B12, and homocysteine with upper gastrointestinal (GI) cancers in a population-based case-control study in Taixing City, China. With informed consent, we recruited cases with cancers of esophagus (n = 218), stomach (n = 206), and liver (n = 204), and one common healthy control group (n = 405). A standardized epidemiologic questionnaire was used in face-to-face interviews, and blood samples were collected during interviews. We observed an inverse association between plasma folate levels and liver cancer. The adjusted odds ratio (aOR) was 0.46 [95% confidence interval (CI) = 0.24-0.88] comparing individuals in the highest quartile to those in the lowest. We found a positive association between plasma vitamin B12 levels and all three cancers. The aORs for those in the highest quartile were 2.80 (95% CI = 1.51-5.18) for esophageal cancer, 2.17 (1.21-3.89) for stomach cancer, and 9.97 (4.82-20.60) for liver cancer, comparing to those in the lowest quartile. We further observed interaction between plasma folate and vitamin B12 on these cancers. Our data indicated associations between plasma folate and vitamin B12 with upper GI cancers in Chinese population. Further research is warranted considering the debate over the necessity of food fortification.

Genetic variation at 8q24 is associated with prostate, bladder, breast, colorectal, thyroid, lung, ovarian, UADT, liver and stomach cancers. However, a role for variation at 8q24 in familial clustering of upper gastrointestinal cancers has not been studied. In order to explore potential inherited susceptibility, we analyzed epidemiologic data from a population-based case-control study of upper gastrointestinal cancers from Taixing, China. The study population includes 204 liver, 206 stomach, and 218 esophageal cancer cases and 415 controls. Associations between 8q24 rs1447295, rs16901979, rs6983267 and these cancers were stratified by family history of cancer. Odds ratios and 95% confidence intervals were adjusted for potential confounders: age, sex, education, tobacco smoking, alcohol consumption, and BMI at interview. We also adjusted for hepatitis B and aflatoxin (liver cancer) and Helicobacter pylori (stomach cancer). In a dominant model, among those with a family history of cancer, rs1447295 was positively associated with liver cancer (OR(adj) 2.80; 95% CI 1.15-6.80). Heterogeneity was observed (P(heterogeneity) = 0.029) with rs6983267 and liver cancer, with positive association in the dominant model among those with a family history of cancer and positive association in the recessive model among those without a family history of cancer. When considered in a genetic risk score model, each additional 8q24 risk genotype increased the odds of liver cancer by two-fold among those with a family history of cancer (OR(adj) 2.00; 95% CI 1.15-3.47). These findings suggest that inherited susceptibility to liver cancer may exist in the Taixing population and that variation at 8q24 might be a genetic component of that inherited susceptibility.

Garlic consumption has been associated inversely with esophageal cancer (EC); however, its interactions with tobacco smoking and alcohol consumption have never been evaluated in an epidemiological study. We evaluated the potential interactions between garlic intake and tobacco smoking as well as alcohol consumption in a population-based case-control study with 2969 incident EC cases and 8019 healthy controls. Epidemiologic data were collected by face-to-face interviews using a questionnaire. The adjusted odds ratio (OR) and 95% confidence interval (CI) were estimated and additive and multiplicative interactions were evaluated using unconditional logistic regression models, adjusting for potential confounding factors. Semi-Bayes (SB) adjustments were used to reduce potential false-positive findings. EC was associated inversely with raw garlic intake [SB-adjusted OR for more than once a week=0.68, 95% CI: 0.57-0.80], with a strong dose-response pattern in the overall analysis and in the stratified analyses by smoking and drinking. EC was associated positively with smoking and alcohol drinking, with SB-adjusted OR of 1.73 (95% CI: 1.62-1.85) and 1.37 (95% CI: 1.28-1.46) in dose-response effects of increased intensity and longer duration of smoking/drinking. Moreover, garlic intake interacts with smoking [synergy index (S)=0.83, 95% CI: 0.67-1.02; ratio of OR=0.88, 95% CI: 0.80-0.98] and alcohol drinking (S=0.73, 95% CI: 0.57-0.93; ratio of OR=0.86, 95% CI: 0.77-0.95) both multiplicatively and additively. Our findings suggested that high intake of raw garlic may reduce EC risk and may interact with tobacco smoking and alcohol consumption, which might shed a light on the development of EC as well as a potential dietary intervention among high-risk smokers and drinkers for EC prevention in the Chinese population.

Although the major risk factors for liver cancer have been established, preventive factors for liver cancer have not been fully explored. We evaluated the association between raw garlic consumption and liver cancer in a large population-based case-control study in Eastern China. The study was conducted in Jiangsu, China, from 2003 to 2010. A total of 2011 incident liver cancer cases and 7933 randomly selected population-controls were interviewed. Epidemiological data including raw garlic intake and other exposures were collected, and serum markers of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection were assayed. Overall, eating raw garlic twice or more per week was inversely associated with liver cancer, with an adjusted odds ratio (aOR) of 0.77 (95% confidence interval (CI): 0.62-0.96) compared to those ingesting no raw garlic or less than twice per week. In stratified analyses, high intake of raw garlic was inversely associated with liver cancer among Hepatitis B surface antigen (HBsAg) negative individuals, frequent alcohol drinkers, those having history of eating mold-contaminated food or drinking raw water, and those without family history of liver cancer. Marginal interactions on an additive scale were observed between low raw garlic intake and HBsAg positivity (attributable proportion due to interaction (AP) = 0.31, 95% CI: -0.01-0.62) and heavy alcohol drinking (AP = 0.28, 95% CI: 0.00-0.57). Raw garlic consumption is inversely associated with liver cancer. Such an association shed some light on the potential etiologic role of garlic intake on liver cancer, which in turn might provide a possible dietary intervention to reduce liver cancer in Chinese population.

Inconsistent evidence has been reported on the role of female hormonal factors in the development of lung cancer. This population-based case-control study evaluated the main effect of menstrual/reproductive factors on the risk of lung cancer, and the effect modification by smoking status. Multivariable unconditional logistic regression models were applied adjusted for age, income, education, county of residence, body mass index, smoking status, pack-years of smoking, and family history of lung cancer. Among 680 lung cancer cases and 1,808 controls, later menopause (at >54 vs. <46 years old) was associated with increased risk of lung cancer (SBOR, semi-Bayes adjusted odds ratio = 1.61, 95% PI, posterior interval = 1.10-2.36). More pregnancies (2 or 3 vs. 0 or 1) was associated with decreased risk (SBOR = 0.71, 95% PI = 0.53, 0.95). Ever being a smoker and having two or fewer pregnancies in one's lifetime could jointly increase the odds of lung cancer (RERI, relative excess risk due to interaction = 1.71, 95% CI = 0.03, 3.38). An increased number of ovulatory cycles was associated with increased risk of lung cancer (SBOR for 13 ovulatory cycles = 1.02, 95% CI = 1.00+, 1.04).

Although tobacco smoking has been reported as a risk factor for liver cancer, few studies have specifically explored the association among Chinese females and the potential interaction between smoking and other risk factors. A population-based case-control study was conducted and 2,011 liver cancer cases and 7,933 healthy controls were enrolled in Jiangsu, China from 2003 to 2010. Epidemiological data were collected, and serum hepatitis B surface antigen (HBsAg) and anti-HCV antibody were measured. Unconditional logistic regression was used to examine association and potential interaction, while semi-Bayes (SB) method was employed to make estimates more conservative. The prevalence of serum HBsAg positivity was 43.2% among cases and 6.5% among controls. The adjusted odds ratios (OR) for ever smoking were 1.62 (95% confidence interval [CI]: 1.33-1.96) among male and 0.82 (95% CI: 0.53-1.26) among female. Age at first cigarette, duration of smoking and pack-years of smoking were all significantly associated with liver cancer among men. Compared to HBsAg-negative never smokers, the adjusted ORs were 1.25 (95% CI: 1.03-1.52) for HBsAg-negative ever smokers, 7.66 (95% CI: 6.05-9.71) for HBsAg-positive never smokers, and 15.68 (95% CI: 12.06-20.39) for HBsAg-positive ever smokers. These different odds ratios indicated super-additive (RERI: 7.77, 95% CI: 3.81-11.73) and super-multiplicative interactions (ROR: 1.64, 95% CI: 1.17-2.30) between hepatitis B virus (HBV) infection and tobacco smoking. Most associations and interactions detected remained statistically significant after SB adjustments. Tobacco smoking and HBV infection positively interact in the development of liver cancer.

Cancer is a major public health burden both globally and in China. The most common cancer-related deaths in China are attributable to cancers of the lung, liver, stomach, and esophagus. Previous epidemiologic studies on cancer in China have often been limited by small sample sizes, inconsistent measurements, and lack of precise and accurate data. The Jiangsu Four Cancers (JFC) Study is a population-based case-control study carried out in an effort to obtain consistent and high-quality data to investigate the life style, behavioral, environmental, and genetic factors associated with the four major cancers in China. The aim of this paper is to describe the overall design of the JFC Study and report selected findings on the major risk factors for cancers. Epidemiologic data were collected from 2003 to 2010 through in-person interviews using a structured questionnaire and blood samples were drawn. Unconditional logistic regression was used to estimate the associations of putative risk factors with risks of cancers of the lung, liver, stomach, and esophagus. The study included 2871 lung cancer cases, 2018 liver cancer cases, 2969 esophageal cancer cases, 2216 stomach cancer cases, and 8019 community controls. Low educational level, low income level, tobacco smoking, alcohol drinking, and family history of cancer were confirmed as risk factors for these major cancers. The JFC Study is one of the largest case-control studies of cancers in the Chinese population and will serve as a rich resource for future research on the four major cancers in China.

Background & aims

The potential interaction between family history of liver cancer and HBV infection on liver cancer has not been fully examined.

Methods

We conducted a population-based case-control study composed of 2011 liver cancer cases and 7933 controls in Jiangsu province, China from 2003 to 2010. Data on major risk or protective factors were collected and HBV/HCV sero-markers were assayed using blood samples. Semi-Bayes (SB) adjustments were applied to provide posterior estimates.

Results

Both family history of liver cancer (adjusted odds ratios [OR]: 4.32, 95% confidence intervals [CI]: 3.25-5.73) and hepatitis B surface antigen (HBsAg) positivity (adjusted OR: 9.94, 95% CI: 8.33-11.87) were strongly associated with liver cancer development. For individuals with different combinations of serological markers, the adjusted ORs were 8.45 (95% CI: 5.16-13.82) for HBsAg- and HBcAb-positive; 7.57 (95% CI: 4.87-11.77) for HBsAg-, HBeAg- and HBcAb-positive; and 3.62 (95% CI: 2.47-5.31) for HBsAg-, HBeAb- and HBcAb-positive, compared to all negatives in HBV serological markers. One log increase in HBV DNA level was associated with 17% increased risk (adjusted OR: 1.17, 95% CI: 1.03-1.32). The SB-adjusted OR of HBV-positive individuals with family history of liver cancer was 41.34 (95% posterior interval [PI]: 23.69-72.12) compared with those HBV-negative without family history. Relative excess risk due to additive interaction, the attributable proportion and synergy index were 73.13, 0.87 and 8.04 respectively. Adjusted ratio of OR for multiplicative interaction was 2.84 (95% CI: 1.41-5.75).

Conclusions

Super-additive and super-multiplicative interactions may exist between family history of liver cancer and HBV infection on the development of liver cancer.

Objectives

Dietary factors are of importance in the development of stomach cancer. This study aims to examine index-based dietary patterns associated with stomach cancer in a Chinese population.

Methods

Using data from a population-based case-control study conducted in Jiangsu Province, China, we included a total of 8432 participants (1900 stomach cancer cases and 6532 controls). Dietary data collected by food frequency questionnaire was evaluated by modified Chinese Healthy Eating Index-2016 (mCHEI-2016) and the US Healthy Eating Index-2015 (HEI-2015). Multiple logistic regression analyses were applied to examine the association of mCHEI-2016 and HEI-2015 with stomach cancer while adjusting for potential confounders. The possible interactions between mCHEI-2016 or HEI-2015 and established risk factors were explored.

Results

Among nonproxy interviews, after adjusting for potential confounding factors, a higher score of sodium, reflecting lower intake per day, was inversely associated with stomach cancer [odds ratio (OR), 0.95; 95% CI, 0.91-0.99 for mCHEI-2016; OR, 0.97; 95% CI, 0.94-0.99 for HEI-2015]. No clear associations with stomach cancer were identified for total scores of HEI-2015 (OR, 0.98; 95% CI, 0.87-1.10 with a 10-point increase, P trend = 0.98) and mCHEI-2016 (OR, 1.05; 95% CI, 0.94-1.17 with a 10-point increase, P trend = 0.22). However, the relation between stomach cancer and the mCHEI-2016 was modified by BMI, with a possible inverse association in normal-weight subjects.

Conclusions

Our findings highlight that reduced intake of dietary sodium would prevent the development of stomach cancer. The data indicate a heterogeneity between normal weight and overweight's dietary factors in relation to stomach cancer.

To investigate the associations between dietary fatty acids and cholesterol consumption and stomach cancer (SC), we analyzed data from a population-based case-control study with a total of 1900 SC cases and 6532 controls. Dietary data and other risk or protective factors were collected by face-to-face interviews in Jiangsu Province, China, from 2003 to 2010. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multiple unconditional logistic regression models and an energy-adjusted method. The joint associations between dietary factors and known risk factors on SC were examined. We observed positive associations between dietary saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), and total cholesterol and the development of SC, comparing the highest versus lowest quarters. Increased intakes of dietary SFAs (p-trend = 0.005; aOR, 1.11; 95% CI, 1.01-1.22 with a 7 g/day increase as a continuous variable) and total cholesterol (p-trend < 0.001; aOR, 1.13; 95% CI, 1.06-1.22 with a 250 mg/day increase as a continuous variable) were monotonically associated with elevated odds of developing SC. Our results indicate that dietary SFAs, MUFAs, and total cholesterol are associated with stomach cancer, which might provide a potential dietary intervention for stomach cancer prevention.