Biomedical subjects

R Alexandra Goldbohm

Publications and source records attributed to R Alexandra Goldbohm.

At least 19 recordsLinked to original sources

PubMed2006

Dietary carotenoids and risk of colorectal cancer in a pooled analysis of 11 cohort studies.

Dietary carotenoids have been hypothesized to protect against epithelial cancers. The authors analyzed the associations between intakes of specific carotenoids (alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein + zeaxanthin, and lycopene) and risk of colorectal cancer using the primary data from 11 cohort studies carried out in North America and Europe. Carotenoid intakes were estimated from food frequency questionnaires administered at baseline in each study. During 6-20 years of follow-up between 1980 and 2003, 7,885 incident cases of colorectal cancer were diagnosed among 702,647 participants. The authors calculated study-specific multivariate relative risks and then combined them using a random-effects model. In general, intakes of specific carotenoids were not associated with colorectal cancer risk. The pooled multivariate relative risks of colorectal cancer comparing the highest quintile of intake with the lowest ranged from 0.92 for lutein + zeaxanthin to 1.04 for lycopene; only for lutein + zeaxanthin intake was the result borderline statistically significant (95% confidence interval: 0.84, 1.00). The associations observed were generally similar across studies, for both sexes, and for colon cancer and rectal cancer. These pooled data did not suggest that carotenoids play an important role in the etiology of colorectal cancer.

Carotenoids↗

PubMed2006

Intake of the major carotenoids and the risk of epithelial ovarian cancer in a pooled analysis of 10 cohort studies.

Carotenoids, found in fruits and vegetables, have the potential to protect against cancer because of their properties, including their functions as precursors to vitamin A and as antioxidants. We examined the associations between intakes of alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein/zeaxanthin and lycopene and the risk of invasive epithelial ovarian cancer. The primary data from 10 prospective cohort studies in North America and Europe were analyzed and then pooled. Carotenoid intakes were estimated from a validated food frequency questionnaire administered at baseline in each study. Study-specific relative risks (RR) were estimated using the Cox proportional hazards model and then combined using a random-effects model. Among 521,911 women, 2,012 cases of ovarian cancer occurred during a follow-up of 7-22 years across studies. The major carotenoids were not significantly associated with the risk of ovarian cancer. The pooled multivariate RRs (95% confidence intervals) were 1.00 (0.95-1.05) for a 600 microg/day increase in alpha-carotene intake, 0.96 (0.93-1.03) for a 2,500 microg/day increase in beta-carotene intake, 0.99 (0.97-1.02) for a 100 microg/day increase in beta-cryptoxanthin intake, 0.98 (0.94-1.03) for a 2,500 microg/day increase in lutein/zeaxanthin intake and 1.01 (0.97-1.05) for a 4,000 microg/day increase in lycopene intake. These associations did not appreciably differ by study (p-values, tests for between-studies heterogeneity >0.17). Also, the observed associations did not vary substantially by subgroups of the population or by histological type of ovarian cancer. These results suggest that consumption of the major carotenoids during adulthood does not play a major role in the incidence of ovarian cancer.

Breast Neoplasms↗

PubMed2006

Methods for pooling results of epidemiologic studies: the Pooling Project of Prospective Studies of Diet and Cancer.

With the growing number of epidemiologic publications on the relation between dietary factors and cancer risk, pooled analyses that summarize results from multiple studies are becoming more common. Here, the authors describe the methods being used to summarize data on diet-cancer associations within the ongoing Pooling Project of Prospective Studies of Diet and Cancer, begun in 1991. In the Pooling Project, the primary data from prospective cohort studies meeting prespecified inclusion criteria are analyzed using standardized criteria for modeling of exposure, confounding, and outcome variables. In addition to evaluating main exposure-disease associations, analyses are also conducted to evaluate whether exposure-disease associations are modified by other dietary and nondietary factors or vary among population subgroups or particular cancer subtypes. Study-specific relative risks are calculated using the Cox proportional hazards model and then pooled using a random- or mixed-effects model. The study-specific estimates are weighted by the inverse of their variances in forming summary estimates. Most of the methods used in the Pooling Project may be adapted for examining associations with dietary and nondietary factors in pooled analyses of case-control studies or case-control and cohort studies combined.

Diet↗

PubMed2006

Risk estimation for carcinogens based on epidemiological data: a structured approach, illustrated by an example on chromium.

It is generally recognized that human, epidemiological data, if available, are preferred as the starting point for quantitative risk analysis above the use of data from animal studies. Although methods to obtain proper risk estimates from epidemiological data are available, several impediments prevent their widespread application. These impediments include unfamiliarity with epidemiological methods and the lack of a structured and transparent approach. We described a framework to conduct quantitative cancer risk assessment based on epidemiological studies in a structured, transparent, and reproducible manner. Important features of the process include a weight-of-the-evidence approach, estimation of the optimal exposure-risk function by fitting a regression model to the epidemiological data, estimation of uncertainty introduced by potential biases and missing information in the epidemiological studies, and calculation of excess lifetime risk through a life table to take into account competing risks. Sensitivity analyses are a useful tool to obtain insight into the impact of assumptions made and the variability of the underlying data. The framework is sufficiently flexible to allow many types of data, ranging from published, sometimes incomplete data to detailed individual data, while maintaining an optimal result, i.e., a state-of-the-art risk estimate with confidence intervals, based on all available evidence of sufficient quality.

Animals↗

PubMed2006

Intakes of vitamins A, C and E and folate and multivitamins and lung cancer: a pooled analysis of 8 prospective studies.

Intakes of vitamins A, C and E and folate have been hypothesized to reduce lung cancer risk. We examined these associations in a pooled analysis of the primary data from 8 prospective studies from North America and Europe. Baseline vitamin intake was assessed using a validated food-frequency questionnaire, in each study. We calculated study-specific associations and pooled them using a random-effects model. During follow-up of 430,281 persons over a maximum of 6-16 years in the studies, 3,206 incident lung cancer cases were documented. Vitamin intakes were inversely associated with lung cancer risk in age-adjusted analyses; the associations were greatly attenuated after adjusting for smoking and other risk factors for lung cancer. The pooled multivariate relative risks, comparing the highest vs. lowest quintile of intake from food-only, were 0.96 (95% confidence interval (CI) 0.83-1.11) for vitamin A, 0.80 (95% CI 0.71-0.91) for vitamin C, 0.86 (95% CI 0.76-0.99) for vitamin E and 0.88 (95% CI 0.74-1.04) for folate. The association with vitamin C was not independent of our previously reported inverse association with beta-cryptoxanthin. Further, vitamin intakes from foods plus supplements were not associated with a reduced risk of lung cancer in multivariate analyses, and use of multivitamins and specific vitamin supplements was not significantly associated with lung cancer risk. The results generally did not differ across studies or by sex, smoking habits and lung cancer cell type. In conclusion, these data do not support the hypothesis that intakes of vitamins A, C and E and folate reduce lung cancer risk.

Antioxidants↗

PubMed2006

Physical activity and risk of ovarian cancer: results from the Netherlands Cohort Study (The Netherlands).

OBJECTIVE: To investigate the association between nonoccupational physical activity and the risk of ovarian cancer among post-menopausal women. METHODS: The Netherlands Cohort Study on Diet and Cancer consists of 62,573 women aged 55-69 years at baseline. Information regarding baseline nonoccupational physical activity and history of sports activity was collected with a self-administered questionnaire in 1986. After 11.3 years of follow-up, 252 cases of invasive epithelial ovarian cancer were available for case-cohort analysis. RESULTS: In multivariate analysis and compared to women who spent less than 30 min per day on physical activity, the rate ratios (RRs) of ovarian cancer for women who spent up to 60, 90 and >90 min per day were 0.78, 0.86 and 0.72, respectively (95% confidence interval (CI) for the top category, 0.48-1.06; p-trend, 0.15). Women who spent more than 2 h per week on recreational biking and walking had a reduced risk of ovarian cancer (RR = 0.65; 95% CI: 0.41-1.01) compared to women who never participated in recreational biking or walking. CONCLUSIONS: These data suggest a modest inverse association between moderate physical activity and ovarian cancer risk. Vigorous physical activity was not associated with ovarian cancer risk.

Aged↗

PubMed2006

A pooled analysis of 12 cohort studies of dietary fat, cholesterol and egg intake and ovarian cancer.

Fat and cholesterol are theorized to promote ovarian carcinogenesis by increasing circulating estrogen levels. Although case-control studies have reported positive associations between total and saturated fat intake and ovarian cancer risk, two cohort studies have observed null associations. Dietary cholesterol and eggs have been positively associated with ovarian cancer risk. A pooled analysis was conducted on 12 cohort studies. Among 523,217 women, 2,132 incident epithelial ovarian cancer cases were identified. Study-specific relative risks (RR) and 95% confidence intervals (CI) were calculated by Cox proportional hazards models, and then pooled using a random effects model. Total fat intake was not associated with ovarian cancer risk (pooled multivariate RR = 1.08, 95% CI 0.86-1.34 comparing > or =45 to 30-<35% of calories). No association was observed for monounsaturated, polyunsaturated, trans-unsaturated, animal and vegetable fat, cholesterol and egg intakes with ovarian cancer risk. A weakly positive, but non-linear association, was observed for saturated fat intake (pooled multivariate RR = 1.29, 95% CI: 1.01-1.66 comparing highest versus lowest decile). Results for histologic subtypes were similar. Overall, fat, cholesterol and egg intakes were not associated with ovarian cancer risk. The positive association for saturated fat intake at very high intakes merits further investigation.

Cholesterol↗

PubMed2006

Nutrition in the prevention of gastrointestinal cancer.

Diet has been hypothesized to play a role in the etiology of gastrointestinal cancer for a long time. Initially, strong evidence of such effects was found in retrospective epidemiological studies. Dietary habits, in particular those from the distant past, are difficult to measure, however. Results from recent, prospective and larger studies of better quality did not always confirm these associations. Consumption of fruits and vegetables appear to have a modest role in the prevention of gastrointestinal cancers. In contrast, the roles of alcohol consumption and overweight on risk of gastrointestinal cancer have become much clearer. Overweight and obesity are important risk factors for adenocarcinoma (but not squamous carcinoma) of the esophagus, gastric cardia carcinoma (but not noncardia carcinoma), and colorectal cancer, the latter in particular among men. Alcohol consumption is a risk factor for squamous carcinoma (but not adenocarcinoma) of the esophagus, gastric cancer and colorectal cancer. Selenium may be inversely related to esophageal and gastric cancer.

Alcohol Drinking↗

PubMed2006

Dietary folate and APC mutations in sporadic colorectal cancer.

Folate deficiency has been associated with colorectal cancer risk and may be involved in colorectal carcinogenesis through increased chromosome instability, gene mutations, and aberrant DNA methylation. Within the Netherlands Cohort Study on diet and cancer, we investigated the associations between dietary folate intake and colorectal cancer risk with (APC(+)) and without (APC(-)) truncating APC mutations, accounting for hMLH1 expression and K-ras mutations. In total, 528 cases and 4200 subcohort members were available for data analyses of the study cohort (n = 120,852) from a follow-up period between 2.3 and 7.3 y after baseline. Adjusted gender-specific incidence rate ratios (RR) over tertiles of folate intake were calculated in case-cohort analyses for colon and rectal cancer. Although relatively high folate intake was not associated with overall colorectal cancer risk, it reduced the risk of APC(-)colon tumors in men (RR 0.58, 95% CI 0.32-1.05, P(trend) = 0.06 for the highest vs. lowest tertile of folate intake). In contrast, it was positively associated with APC(+) colon tumors in men (highest vs. lowest tertile: RR 2.77, 95% CI 1.29-5.95, P(trend) = 0.008) and was even stronger when the lack of hMLH1 expression and K-ras mutations were excluded (RR 3.99, 95% CI 1.43-11.14, P(trend) = 0.007). Such positive associations were not observed among women; nor was folate intake associated with rectal cancer when APC mutation status was taken into account. Relatively high folate consumption reduced the risk of APC(-) colon tumors, but folate intake was positively associated with APC(+) colon tumors among men. These opposite results may indicate that folate enhances colorectal carcinogenesis through a distinct APC mutated pathway.

Adaptor Proteins, Signal Transducing↗

PubMed2006

Dairy products and ovarian cancer: a pooled analysis of 12 cohort studies.

BACKGROUND: Dairy foods and their constituents (lactose and calcium) have been hypothesized to promote ovarian carcinogenesis. Although case-control studies have reported conflicting results for dairy foods and lactose, several cohort studies have shown positive associations between skim milk, lactose, and ovarian cancer. METHODS: A pooled analysis of the primary data from 12 prospective cohort studies was conducted. The study population consisted of 553,217 women among whom 2,132 epithelial ovarian cases were identified. Study-specific relative risks and 95% confidence intervals were calculated by Cox proportional hazards models and then pooled by a random-effects model. RESULTS: No statistically significant associations were observed between intakes of milk, cheese, yogurt, ice cream, and dietary and total calcium intake and risk of ovarian cancer. Higher lactose intakes comparing > or = 30 versus <10 g/d were associated with a statistically significant higher risk of ovarian cancer, although the trend was not statistically significant (pooled multivariate relative risk, 1.19; 95% confidence interval, 1.01-1.40; P(trend) = 0.19). Associations for endometrioid, mucinous, and serous ovarian cancer were similar to the overall findings. DISCUSSION: Overall, no associations were observed for intakes of specific dairy foods or calcium and ovarian cancer risk. A modest elevation in the risk of ovarian cancer was seen for lactose intake at the level that was equivalent to three or more servings of milk per day. Because a new dietary guideline recommends two to three servings of dairy products per day, the relation between dairy product consumption and ovarian cancer risk at these consumption levels deserves further examination.

Calcium, Dietary↗

PubMed2006

Heme and chlorophyll intake and risk of colorectal cancer in the Netherlands cohort study.

BACKGROUND: The evidence for red meat as a determinant of colorectal cancer remains equivocal, which might be explained by differences in heme content. Heme is the pro-oxidant, iron-containing porphyrin pigment of meat and its content depends on the type of meat. Chlorophyll from green vegetables might modify this association. METHODS: The Netherlands Cohort Study was initiated in 1986 when a self-administered questionnaire on risk factors for cancer was completed by 120,852 subjects ages 55 to 69 years. After 9.3 years of follow-up through the Cancer Registry, 1,535 incident colorectal cancer cases (869 men and 666 women) were available. Nineteen of the 150 items in the validated dietary questionnaire related to consumption of specific types of fresh and processed meat. Heme iron content was calculated as a type-specific percentage of the total iron content and chlorophyll content of vegetables was derived from the literature. RESULTS: Multivariate rate ratios for quintiles of heme iron intake and colon cancer were 1.00, 0.98, 1.04, 1.13, and 1.29 (P(trend) = 0.10) among men and 1.00, 1.31, 1.44, 1.18, and 1.20 (P(trend) = 0.56) among women, respectively. No consistent associations were observed for rectal cancer. Rate ratios for colon cancer increased across successive quintiles of the ratio of heme/chlorophyll among men only (1.00, 1.08, 1.01, 1.32, and 1.43; P(trend) = 0.01). No associations were observed between fresh meat and colorectal cancer. CONCLUSION: Our data suggest an elevated risk of colon cancer in men with increasing intake of heme iron and decreasing intake of chlorophyll. Further research is needed to confirm these results.

Aged↗

PubMed2006

Nitrate intake does not influence bladder cancer risk: the Netherlands cohort study.

OBJECTIVES: N-nitroso compounds, endogenously formed from nitrate-derived nitrite, are suspected to be important bladder carcinogens. However, the association between nitrate exposure from food or drinking water and bladder cancer has not been substantially investigated in epidemiologic studies. METHODS: We evaluated the associations between nitrate exposure and bladder cancer in the Netherlands Cohort Study, conducted among 120,852 men and women, 55-69 years of age at entry. Information on nitrate from diet was collected via a food frequency questionnaire in 1986 and a database on nitrate content of foods. Individual nitrate exposures from beverages prepared with tap water were calculated by linking the postal code of individual residence at baseline to water company data. After 9.3 years of follow-up and after excluding subjects with incomplete or inconsistent dietary data, 889 cases and 4,441 subcohort members were available for multivariate analyses. We calculated incidence rate ratios (RR) and corresponding 95% confidence intervals (CIs) using Cox regression analyses. We also evaluated possible effect modification of dietary intake of vitamins C and E (low/high) and cigarette smoking (never/ever). RESULTS: The multivariate RRs for nitrate exposure from food, drinking water, and estimated total nitrate exposure were 1.06 (95% CI, 0.81-1.31), 1.06 (95% CI, 0.82-1.37), and 1.09 (95% CI, 0.84-1.42), respectively, comparing the highest to the lowest quintiles of intake. Dietary intake of vitamins C and E (low/high) and cigarette smoking (never/ever) had no significant impact on these results. CONCLUSION: Although the association between nitrate exposure and bladder cancer risk is biologically plausible, our results in this study do not support an association between nitrate exposure and bladder cancer risk.

Aged↗

PubMed2005

Dietary fiber intake and risk of colorectal cancer: a pooled analysis of prospective cohort studies.

CONTEXT: Inconsistent findings from observational studies have continued the controversy over the effects of dietary fiber on colorectal cancer. OBJECTIVE: To evaluate the association between dietary fiber intake and risk of colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS: From 13 prospective cohort studies included in the Pooling Project of Prospective Studies of Diet and Cancer, 725,628 men and women were followed up for 6 to 20 years across studies. Study- and sex-specific relative risks (RRs) were estimated with the Cox proportional hazards model and were subsequently pooled using a random-effects model. MAIN OUTCOME MEASURE: Incident colorectal cancer. RESULTS: During 6 to 20 years of follow-up across studies, 8081 colorectal cancer cases were identified. For comparison of the highest vs lowest study- and sex-specific quintile of dietary fiber intake, a significant inverse association was found in the age-adjusted model (pooled RR = 0.84; 95% confidence interval [CI], 0.77-0.92). However, the association was attenuated and no longer statistically significant after adjusting for other risk factors (pooled multivariate RR = 0.94; 95% CI, 0.86-1.03). In categorical analyses compared with dietary fiber intake of 10 to <15 g/d, the pooled multivariate RR was 1.18 (95% CI, 1.05-1.31) for less than 10 g/d (11% of the overall study population); and RR, 1.00 (95% CI, 0.85-1.17) for 30 or more g/d. Fiber intake from cereals, fruits, and vegetables was not associated with risk of colorectal cancer. The pooled multivariate RRs comparing the highest vs lowest study- and sex-specific quintile of dietary fiber intake were 1.00 (95% CI, 0.90-1.11) for colon cancer and 0.85 (95% CI, 0.72-1.01) for rectal cancer (P for common effects by tumor site = .07). CONCLUSIONS: In this large pooled analysis, dietary fiber intake was inversely associated with risk of colorectal cancer in age-adjusted analyses. However, after accounting for other dietary risk factors, high dietary fiber intake was not associated with a reduced risk of colorectal cancer.

Colorectal Neoplasms↗

PubMed2005

Vegetable and fruit consumption and risk of renal cell carcinoma: results from the Netherlands cohort study.

Vegetable and fruit consumption is generally inversely associated with various cancer types, including renal cell carcinoma (RCC). The Netherlands cohort study on diet and cancer (NLCS) consists of 120,852 men and women, aged 55-69 years, who filled out a self-administered questionnaire that includes 150-item food-frequency questions and additional questions on lifestyle factors, at baseline in 1986. A case-cohort approach was used. After 9.3 years of follow-up, 275 microscopically confirmed incident cases were identified. Subjects with incomplete or inconsistent dietary data were excluded, leaving 260 RCC cases for analyses on fruit consumption and 249 RCC cases for analyses on vegetable consumption. Incidence rate ratios (RR) and corresponding 95% confidence intervals (CI) were estimated using Cox proportional hazard models. RRs for exposure variables are expressed per increment of 25 g/day and are adjusted for age, sex, smoking, body mass index and history of hypertension at baseline. The RRs for vegetable consumption were further adjusted for fruit consumption and vice versa. Total vegetable and fruit consumption (RR: 1.00; 95% CI 0.97-1.02), vegetable (RR: 1.00, 95% CI 0.96-1.06) and fruit consumption (RR: 1.00; 95% CI 0.97-1.03) were not associated with RCC risk. Also, no association existed for botanical subgroups of vegetables and fruit. For 30 individual vegetables and fruits, we observed one that significantly increased RR (mandarin consumption, RR: 1.76; 95% CI 1.28-2.42), which must be regarded cautiously because of multiple testing. These results suggest the absence of an association between vegetable and/or fruit consumption and RCC risk.

Carcinoma, Renal Cell↗

PubMed2005

Consumption of vegetables and fruits and risk of ovarian carcinoma.

BACKGROUND: To the authors' knowledge, only a few prospective studies to date have investigated the correlation between vegetable and fruit consumption and the risk of ovarian carcinoma and their results have been inconclusive. METHODS: Vegetable and fruit intake was assessed in relation to ovarian carcinoma, among 62,573 postmenopausal women participating in The Netherlands Cohort Study on Diet and Cancer. Women reported on dietary habits and on other risk factors for cancer in a self-administered questionnaire in 1986. Follow-up of cancer was implemented by annual record linkage with The Netherlands Cancer Registry and a pathology register. After 11.3 years of follow-up, data regarding 252 incident invasive epithelial ovarian carcinoma cases and of 2216 subcohort members were available for case-cohort analyses. RESULTS: Multivariable-adjusted rate ratios (RR) of ovarian carcinoma for women in the highest compared with the lowest quintile of intake (RR(Q5 vs. Q1)) were 0.98 (95% confidence interval [95% CI], 0.61-1.58) for total vegetables and 1.11 (95% CI, 0.70-1.78) for total fruit. The RR(Q5 vs. Q1) values of ovarian carcinoma with intake of cooked vegetables, raw vegetables, brassicas, legumes, cooked leafy vegetables, and raw leafy vegetables were 1.35 (95% CI, 0.83-2.21), 0.75 (95% CI, 0.48-1.18), 1.42 (95% CI, 0.88-2.29), 0.93 (95% CI, 0.60-1.44), 1.05 (95% CI, 0.66-1.67), and 1.23 (95% CI, 0.75-2.02), respectively. With the exception of raw endive (multivariable-adjusted RR, 0.24; 95% CI, 0.07-0.78), none of the individual vegetable or fruit items showed a statistically significant association with ovarian carcinoma. CONCLUSIONS: The results of the current study did not support a significant association between vegetable or fruit consumption and ovarian carcinoma risk in a cohort of postmenopausal women.

Adult↗

PubMed2005

Dietary folate intake and k-ras mutations in sporadic colon and rectal cancer in The Netherlands Cohort Study.

We studied the association between dietary folate and specific K-ras mutations in colon and rectal cancer in The Netherlands Cohort Study on diet and cancer. After 7.3 years of follow-up, 448 colon and 160 rectal cancer patients and 3,048 sub-cohort members (55-69 years at baseline) were available for data analyses. Mutation analysis of the K-ras gene was carried out on all archival adenocarcinoma specimens. Case-cohort analyses were used to compute adjusted incidence rate ratios (RR) and 95% confidence intervals (CI) for colon and rectal cancer overall and for K-ras mutation status subgroups according to 100 mug/day increased intake in dietary folate. Dietary folate intake was not significantly associated with colon cancer risk for men or women, neither overall nor with K-ras mutation status. For rectal cancer, folate intake was associated with a decreased disease risk in men and was most pronounced for K-ras mutated tumors, whereas an increased association was observed for women. Regarding the K-ras mutation status in women, an increased association was observed for both wild-type and mutated K-ras tumors. Specifically, folate intake was associated with an increased risk of G>T and G>C transversions in rectal tumors (RR = 2.69, 95% CI = 1.43-5.09), but inversely associated with G>A transitions (RR = 0.08, 95% CI = 0.01-0.53). Our data suggest that the effect of folate on rectal cancer risk is different for men and women and depends on the K-ras mutation status of the tumor.

Aged↗

PubMed2005

Cigarette smoking and colorectal cancer: APC mutations, hMLH1 expression, and GSTM1 and GSTT1 polymorphisms.

The contribution of cigarette smoking to sporadic colorectal cancer may differ according to molecular aspects of the tumor or according to glutathione S-transferase M1 (GSTM1) or glutathione S-transferase T1 (GSTT1) genotype. In the prospective Netherlands Cohort Study on Diet and Cancer, adjusted incidence rate ratios for 1986-1993 were computed for overall colorectal cancer, tumors with and without adenomatous polyposis coli (APC) mutations, and tumors with and without human mut-L homologue 1 (hMLH1) expression, according to cigarette smoking characteristics (661 cases, 2,948 subcohort members). Case-only analyses were performed to estimate odds ratios for interaction between cigarette smoking and GSTM1 and GSTT1 genotypes. In comparison with never smokers, a high smoking frequency increased the risk of colorectal cancer (for a five-cigarette/day increment, incidence rate ratio (IRR) = 1.07, 95% confidence interval (CI): 1.03, 1.12), and this association was stronger in 371 tumors without a truncating APC mutation (IRR = 1.11, 95% CI: 1.05, 1.17). Long-term smoking was associated with lack of hMLH1 expression in 56 tumors (for a 10-year increment, IRR = 1.17, 95% CI: 1.00, 1.37). No statistically significant interactions between smoking and GSTM1 or GSTT1 genotype were observed. These results indicate that cigarette smoking is associated with risk of colorectal cancer, and this association may depend on molecular characteristics of the tumor as defined by APC mutation and hMLH1 expression status.

Adaptor Proteins, Signal Transducing↗

PubMed2005

Meat and fish consumption, APC gene mutations and hMLH1 expression in colon and rectal cancer: a prospective cohort study (The Netherlands).

OBJECTIVE: The aim of this study was to investigate the associations between meat and fish consumption and APC mutation status and hMLH1 expression in colon and rectal cancer. METHODS: The associations were investigated in the Netherlands Cohort Study, and included 434 colon and 154 rectal cancer patients on whom case-cohort analyses (subcohort n = 2948) were performed. RESULTS: Total meat consumption was not associated with the endpoints studied. Meat product (i.e. processed meat) consumption showed a positive association with colon tumours harbouring a truncating APC mutation, whereas beef consumption was associated with an increased risk of colon tumours without a truncating APC mutation (incidence rate ratio (RR) highest versus lowest quartile of intake 1.61, 95% confidence interval (CI) 0.96-2.71, p-trend = 0.04 and 1.58, 95% CI 1.10-2.25, p-trend = 0.01, respectively). Consumption of other meat (horsemeat, lamb, mutton, frankfurters and deep-fried meat rolls) was associated with an increased risk of rectal cancer without a truncating APC mutation (RR intake versus no intake 1.79, 95% CI 1.10-2.90). No associations were observed for meat consumption and tumours lacking hMLH1 expression. CONCLUSIONS: Our data indicate that several types of meat may contribute differently to the aetiology of colon and rectal cancer, depending on APC mutation status but not hMLH1 expression of the tumour.

Adaptor Proteins, Signal Transducing↗