Meat intake, preparation methods, mutagens and colorectal adenoma recurrence

Red meat intake has been shown to be associated with higher risk of colorectal cancer. Though the exact mechanisms responsible for this association remain unknown, several tumorigenic properties of meat have been proposed. One well-supported biologic mechanism is elevated exposure to the genotoxic formation of heterocyclic amines (HCAs), which occur when meat is cooked at high temperatures for a long period of time. We prospectively assessed the relation between type of meat, meat preparation method, doneness, a metric of HCAs and other mutagens and colorectal adenoma recurrence among 869 participants in a chemoprevention trial of ursodeoxycholic acid. Unconditional logistic regression analyses were used to estimate odds ratios (ORs) and associated 95% confidence intervals (CIs). Most meat variables assessed were positively but weakly associated with recurrence of any adenoma. In contrast, recurrence of advanced or multiple adenomas was more strongly associated with a number of the meat exposure variables evaluated. For recurrence of advanced lesions, significant associations were detected among individuals in the highest when compared with the lowest tertile of intake for pan-fried red meat (OR = 1.85; 95% CI = 1.10-3.13) and well/very well done red meat (OR = 1.71; 95% CI = 1.02-2.86). Significant positive associations were shown for recurrence of multiple adenomas and the following variables: processed meat (OR = 1.83; 95% CI = 1.10-3.04), pan-fried red meat (OR = 1.63; 95% CI = 1.01-2.61), well/very well done red meat (OR = 1.68; 95% CI = 1.03-2.74), 2-amino-3,4,8-trimethylimidazo[4,5,-f]quinoxaline (OR = 1.74; 95% CI = 1.07-2.82) and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (OR = 1.68; 95% CI = 1.03-2.75). Our results support a meat mutagen exposure hypothesis as a potential mechanism for recurrence of clinically significant adenomatous polyps.     

Meat, cooking methods and colorectal cancer: a case-referent study in Stockholm

The associations between methods of cooking meats and colorectal cancer were examined in a population-based case-referent study performed in Stockholm in 1986-1988. The study included 559 cases and 505 referents. Total meat intake, frequent consumption of brown gravy, and a preference for a heavily browned meat surface each independently increased the risk for colorectal cancer. The relative risks (RR) were higher for rectal than for colon cancer, and for boiled meat (RR colon = 1.7, RR rectum = 2.7) than for meat fried with a medium or lightly browned surface (RR colon = 0.8, RR rectum = 1.1), but the highest risks were for meat fried with a heavily browned surface (RR colon = 2.8, RR rectum = 6.0). The analyses were adjusted for year of birth, gender and fat intake. Further adjustments for total energy, dietary fiber intake, body mass and physical activity had little or no influence on the results. The findings suggest that, in addition to frequent meat intake, a heavily browned meat surface formed when frying meat at high temperatures is important in the etiology of colorectal cancer.     

Processed meat intake, CYP2A6 activity and risk of colorectal adenoma

Red and processed meat intake is associated with increased risks of both colorectal adenoma and cancer. Processed meats contain nitrate and nitrite, precursors of N-nitroso compounds (NOCs); furthermore, meats cooked at high temperatures contain heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs). Specific NOC, HCA and PAH are mutagens and animal carcinogens. We conducted a case-control study of 146 cases of colorectal adenoma, diagnosed at sigmoidoscopy or colonoscopy, and 228 polyp-free controls. We calculated odds ratios (ORs) [and 95% confidence intervals (CIs)] and found a 2-fold increased risk in the highest, compared with the lowest, quartile of processed meat intake (95% CI = 1.0-4.0). We estimated nitrate and nitrite intake from meat using published data from the literature as well as from actual measurements of meats analyzed recently. We evaluated the interaction of processed meat and nitrate plus nitrite intake with CYP2A6 activity, an enzyme able to metabolize some NOC to their carcinogenic form. Results for both methods of estimating nitrate and nitrite intake were similar; compared with the lowest, the highest quartile based on measured values was associated with a 2-fold elevated risk (95% CI = 1.0-3.9). Adjustment for the HCA 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) attenuated the association (OR = 1.6, 95% CI = 0.8-3.2), but other HCA and PAH had minimal effect. Higher CYP2A6 activity was not associated with risk and there was no evidence of an interaction of CYP2A6 activity with nitrate and nitrite intake. Our results suggest that nitrite and nitrate intake from processed meat intake increases the risk of colorectal adenoma after accounting for HCA and PAH.     

Meat intake, cooking-related mutagens and risk of colorectal adenoma in a sigmoidoscopy-based case-control study

Reported habits of red meat consumption, particularly red meat that has been cooked to the degree termed 'well-done', is a positive risk factor for colorectal cancer. Under high, pyrolytic temperatures, heterocyclic amines (HCA) and benzo[a]pyrene (BP) molecules can form inside and on the surface of red meat, respectively. These compounds are precursors that are metabolically converted to compounds known to act as mutagens and carcinogens in animal models, yet their role in human colorectal carcinogenesis remains to be clarified. We investigated whether intake of these compounds is associated with risk of colorectal adenoma in the context of a polyp-screening study conducted in Southern California. Using a database of individual HCAs and BP in meats of various types and subjected to specified methods and degrees of cooking, we estimated nanogram consumption of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, 2-amino-3,4,8-trimethylimidazo[4,5-f] quinoxaline, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline and benzo[a]pyrene (BP). We observed a 6% increased risk of large (>1 cm) adenoma per 10 ng/day consumption of BP [OR = 1.06 (95% CI, 1.00-1.12), P (trend) = 0.04]. A major source of BP is red meat exposed to a naked flame, as occurs during the barbecuing process. Consistent with this finding an incremental increase of 10 g of barbecued red meat per day was associated with a 29% increased risk of large adenoma [OR = 1.29 (95% CI, 1.02-1.63), P (trend) = 0.04]. Individuals in the top quintile of barbecued red meat intake were at increased risk of large adenoma [OR = 1.90 (95% CI, 1.04-3.45)], compared with never consuming barbecued red meat. The consumption of oven-broiled red meat was inversely related to adenoma risk compared with non-consumers [OR = 0.49 (95% CI, 0.28-0.85)]. We did not identify any association with consumption of individual HCAs and colorectal adenoma risk. These results support the hypothesis that BP contributes to colorectal carcinogenesis.     

Meat, metabolic genotypes and risk for colorectal cancer.

Persuasive data exist as to the importance of environmental factors in the pathogenesis of sporadic colorectal cancer. One possibility is that the effect of environmental factors varies between individuals, perhaps on the basis of inherited variation (polymorphism) in genes which influence the activation or inactivation of dietary carcinogens. Thus far, the focus has been on acetylator genes (NAT1, NAT2) and the activation of heterocyclic amines, carcinogens generated by cooking meat for prolonged periods at high temperature. Three case-control studies and one prospective study have shown a consistent trend towards higher risks for cancer with higher intakes of meat in rapid acetylators for NAT1, NAT2 or both genotypes. Other links between meat, cooking methods, metabolic genotypes and risk for cancer might include enhanced activation of polycyclic aromatic hydrocarbons and N-nitroso compounds by variant genotypes of CYP1A1 and CYP2E1, respectively, and modulation by meat of the protective effect of the E4 allele of apolipoprotein E on risk for cancer of the proximal colon.     

No effect of meat,meat cooking preferences,meat mutagens or heme iron on lung cancer risk in the prostate,lung, colorectal and ovarian cancer screening trial

Recent epidemiological studies have suggested that red and processed meat may increase the risk of lung cancer. Possible underlying mechanisms include mutagens produced during high‐temperature cooking or preservation, or formed endogenously from heme iron in meat. We used data from 99,579 participants of both screened and nonscreened arms of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, aged 55–74 years, to investigate whether meat type, cooking method, doneness level, intake of specific meat mutagens 2‐amino‐3,8‐dimethylimidazo[4,5‐f]quinoxaline (MeIQx), 2‐amino‐3,4,8‐trimethylimidazo[4,5‐f]quinoxaline] (DiMeIQx), 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP) and benzo(a)pyrene (B(a)P)] and heme iron are associated with lung cancer. Participants' diet was assessed prospectively using a 124‐item food frequency questionnaire and an additional meat‐cooking module. Dietary data were used in conjunction with a database to estimate intake of MeIQx, DiMeIQx, PhIP, B(a)P and heme iron. After up to 8 years of follow‐up, 782 incident lung cancer cases were ascertained. Lung cancer risk was not associated with the consumption of either red (men: HR_{Q5 vs. Q1} = 1.11, 95% CI = 0.79–1.56, P_trend = 0.42; women: HR_{Q5 vs. Q1} = 1.30, 95% CI = 0.87–1.95, P_trend = 0.65) or processed meat (men: HR_{Q5 vs. Q1} = 1.12, 95% CI = 0.83–1.53, P_trend = 0.22; women: HR_{Q5 vs. Q1} = 0.98, 95% CI = 0.68–1.41, P_trend = 0.32) in multivariable models. High‐temperature cooking methods, level of meat doneness, meat mutagens and heme iron had no effect on lung cancer risk. In this population, we found no association between meat type, cooking method, doneness level or intake of specific meat mutagens or heme iron and lung cancer risk.     

Insulin resistance, apoptosis, and colorectal adenoma risk.

Compelling evidence from epidemiologic studies indicates that elevated circulating insulin-like growth factor (IGF)-I, insulin resistance, and associated complications, such as elevated fasting plasma insulin, glucose and free fatty acids, glucose intolerance, increased body mass index, and visceral adiposity, are linked with increased risk of colorectal cancer. However, the role of insulin and markers of glucose control in the development of adenomas, precursors to colorectal cancer, has not been fully explored. We evaluated the relationship between plasma insulin, glucose, IGF-I, IGF-II, IGF-binding protein-3 (IGFBP-3), apoptosis, and colorectal adenomas in a case-control study. Participants were drawn from consenting patients undergoing colonoscopy at the University of North Carolina hospitals (Chapel Hill, NC). Participants were classified as cases or controls based on whether they had one or more colorectal adenomatous polyps. Fasting plasma insulin, IGF-I, IGF-II, and IGFBP-3 levels were assessed by ELISA. Glucose was measured by glucose hexokinase assay. Apoptosis was assessed by morphology on H&E-stained sections. Dietary and lifestyle information were obtained by telephone interview. Logistic regression was used to examine the association between adenoma status and insulin-IGF markers. Adenoma cases (n = 239) and adenoma-free controls (n = 517) provided rectal biopsies and/or blood samples and interview data. Consistent with prior findings, cases were more likely to be males, older, have higher waist-to-hip ratio, lower calcium intake, lower apoptosis, and less likely to report nonsteroidal anti-inflammatory drug use. Those in the highest quartile of insulin (adjusted odds ratio, 2.2; 95% confidence interval, 1.1-4.2) and glucose (adjusted odds ratio, 1.8; 95% confidence interval, 0.9-3.6) were more likely to have an adenoma compared with the lowest quartile. Similarly, subjects in the highest two quartiles of insulin were more likely to be in the lowest two quartiles of apoptosis. Overall, there were no significant differences between mean circulating levels of glucose, IGF-I, IGF-II, and IGFBP-3 among cases and controls and no association between these variables and apoptosis. The results provide novel evidence that elevated insulin and glucose are associated with increased adenoma risk and decreased apoptosis in normal rectal mucosa. These findings suggest that insulin may act early in the adenoma-carcinoma sequence to promote the development of colorectal adenoma by decreasing apoptosis in the normal mucosa.     

Television watching and risk of colorectal adenoma

Background:

Prolonged TV watching, a major sedentary behaviour, is associated with increased risk of obesity and diabetes and may involve in colorectal carcinogenesis.

Methods:

We conducted a cross-sectional analysis among 31 065 men with ⩾1 endoscopy in the Health Professionals Follow-up Study (1988–2008) to evaluate sitting while watching TV and its joint influence with leisure-time physical activity on risk of colorectal adenoma. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs).

Results:

Prolonged sitting while watching TV was significantly associated with increased risk of colorectal adenoma (n=4280), and adjusting for physical activity or a potential mediator body mass index did not change the estimates. The ORs (95% CIs) across categories of TV watching (0–6, 7–13, 14–20, and 21+ h per week) were 1.00 (referent), 1.09 (1.01–1.17), 1.16 (1.06–1.27), and 1.10 (0.97–1.25) (OR per 14-h per week increment=1.11; 95% CI: 1.04–1.18; P_trend=0.001). Compared with the least sedentary (0–6 h per week of TV) and most physically active (highest quintile) men, the most sedentary (14+ h per week) and least active (lowest quintile) men had a significant increased risk of adenoma (OR=1.25; 95% CI: 1.05–1.49), particularly for high-risk adenoma.

Conclusions:

Prolonged TV viewing is associated with modest increased risk of colorectal adenoma independent of leisure-time physical activity and minimally mediated by obesity.     

Meat intake, heterocyclic amines and risk of colorectal cancer

A case-control study was conducted in Uruguay, in order to investigate the relationship between heterocyclic amine intake and colorectal cancer risk. The study included 250 cases of colorectal cancer and 500 controls, frequency-matched with the cases on age, sex, and residence. A significant increase in risk of colorectal cancer associated with red meat, beef and fried meat was observed. Heterocyclic amines were associated with a significant increase in the risk of colorectal cancer in males and females. This increased risk persisted after controlling for total energy, total meat and total fat intake. On the other hand, total meat and total fat intake were not longer significant. This latter finding suggests that heterocyclic amine exposure is central in colorectal carcinogenesis.     

Urinary prostaglandin E2 metabolite and risk for colorectal adenoma

COX-2 is upregulated in most colorectal cancers. Most of the COX-2 tumor-inducing effects are believed to be mediated through overproduction of prostaglandin E(2) (PGE(2)), which can be measured using a urinary metabolite of PGE(2), PGE-M. Urinary PGE-M was assessed in a case-control study of colorectal adenoma. Included in the analysis were 224 cases with at least one advanced adenoma, 152 cases with multiple small tubular adenomas, 300 cases with only a single small tubular adenoma, and 364 polyp-free controls. There were no statistical differences in PGE-M levels between controls and cases with a single small tubular adenoma. However, cases with either an advanced adenoma or multiple small tubular adenomas had more than 25% higher levels of PGE-M than controls. Participants with the highest quartile level of PGE-M were approximately 2.5-fold more likely to have advanced or multiple small tubular adenoma in comparison with those with the lowest level of PGE-M [OR = 2.53; 95% confidence interval (CI), 1.54-4.14; P(trend) < 0.001]. The association was strongest among women. PGE-M level was associated with increased risk for multiple or advanced adenoma but not single small adenoma. Our study suggests that PGE-M may be a useful risk marker for assessing the risk of harboring clinically more important versus less important colorectal neoplasia.     

Coffee intake and the risk of colorectal adenoma: The colorectal adenoma study in Tokyo

Coffee is a commonly consumed beverage which contains several potential anticarcinogenic and chemopreventive compounds, and has been hypothesized to have protective effects in colorectal neoplasia. However, the limited available data on coffee consumption in relation to colorectal adenoma (CRA), a precursor lesion to most colorectal cancers, remain largely inconsistent. In this study, we evaluated the association of coffee intake with the risk of CRA in a middle‐aged Japanese population. Study subjects were selected from examinees who underwent total colonoscopy as part of a cancer screening program and responded to self‐administered dietary and lifestyle questionnaires. A total of 738 patients with adenoma and 697 controls were included in the study. Coffee intake was assessed with a food frequency questionnaire, and divided into quartiles based on the distribution among controls. Unconditional logistic regression models were used to estimate odds ratio (OR) and 95% confidence interval (CI) of CRA, with adjustment for potential confounding factors. High coffee consumption was associated with a reduced risk of CRA, with a multivariate‐adjusted OR for the highest versus lowest quartile of coffee intake of 0.67 (95% CI = 0.48–0.93; p_trend = 0.02). The inverse association of coffee intake was limited to proximal (OR = 0.64; 95%CI = 0.44–0.95; p_trend = 0.04) and distal colon adenoma (OR = 0.62; 95%CI = 0.39–0.99; p_trend = 0.06), and appeared to be more evident with small (OR = 0.68; 95%CI = 0.49–0.96; p_trend = 0.04) and single adenomas (OR = 0.65; 95%CI = 0.44–0.95; p_trend = 0.02). Green tea intake was not found to be associated with CRA risk. This study provides support for the protective effect of coffee drinking on colon adenomas, a precursor of colon cancer.     

Leptin concentrations, leptin receptor polymorphisms, and colorectal adenoma risk.

Obesity has been shown to be associated with an increased risk of both colorectal cancer and adenomatous polyps. One mechanism underlying this relationship may involve the growth-promoting effects of the circulating hormones associated with obesity, such as leptin. We conducted a gastroenterology clinic-based, case-control study to evaluate the relationship between circulating leptin concentrations and colorectal adenoma risk; in addition, we evaluated the relationship between leptin receptor polymorphisms and adenoma risk. Individuals with adenomas (n = 157) and colonoscopy-negative controls (n = 191), who had a clinically indicated colonoscopy, were recruited from a large health maintenance organization in the Seattle metropolitan area from 1999 to 2003. Odds ratios and 95% confidence intervals were obtained using logistic regression, adjusting for age at diagnosis, body mass index, family history of colorectal cancer, smoking history, nonsteroidal anti-inflammatory drug use, physical activity, and, among women, menopausal status and postmenopausal hormone use. Among men, those in the highest tertile of leptin concentrations had a 3.3-fold (95% confidence interval, 1.2-8.7) increased adenoma risk compared with those in the lowest tertile (P trend = 0.01). There were no associations between leptin concentrations and adenoma risk in women. There were no associations of leptin receptor genotypes or haplotypes and adenoma risk. The results of this study suggest that, in men, leptin may be associated with risk of colorectal adenomas.     

Microsomal epoxide hydrolase polymorphisms and risk for advanced colorectal adenoma.

Cigarette smoking is a risk factor for colorectal adenoma, a precursor of colorectal cancer. Microsomal epoxide hydrolase (EPHX1) metabolizes polycyclic aromatic hydrocarbons, carcinogens found in cigarette smoke. Nonsynonymous variants of EPHX1 at Tyr(113)His (exon 3) and His(139)Arg (exon 4) are associated, respectively, with low ((113)His) and high ((139)Arg) predicted activity. Among participants randomized to the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, we evaluated risks for advanced adenoma in relation to cigarette use and these two EPHX1 variants. We compared 772 cases with advanced adenoma (adenoma >/=1 cm or containing high-grade dysplasia or villous, including tubulovillous, elements) of the distal colon (left-sided, descending colon and sigmoid or rectum) to 777 gender- and age-matched controls who were screen-negative for left-sided adenoma. Compared to those with homozygous genotypes predicting low EPHX1 activity, advanced adenoma risks tended to be elevated for carriers of (113)TyrTyr [odds ratios (OR), 1.5; 95% confidence intervals (CI), 1.0-2.2] and (139)ArgArg (OR, 1.4; 95% CI, 0.8-2.5) and for subjects who carried a greater number of the alleles ((113)Tyr or (139)Arg) associated with high predicted enzymatic activity (P(trend) = 0.03). The increased risk associated with the increasing number of putative high-activity alleles was most apparent among current and recent (quit <10 years) cigarette smokers (P(trend) = 0.02). In conclusion, EPHX1 variants at codon 113 and 139 associated with high predicted enzymatic activity appear to increase risk for colorectal adenoma, particularly among recent and current smokers.     

Meat intake, meat mutagens and risk of lung cancer in Uruguayan men

Objective  

To determine the role of meat consumption and related mutagens in the etiology of lung cancer, we conducted a case–control study among Uruguayan males in the time period 1996–2004.     

Is metabolic syndrome a risk factor for colorectal adenoma?

BACKGROUND AND AIMS: Epidemiologic studies provide evidence for a link between obesity or diabetes and the risk for colorectal cancer. However, there is a lack of information about the relationship between metabolic syndrome and colorectal adenoma. Therefore, we investigated whether metabolic syndrome is a risk factor for colorectal adenoma. METHODS: We did a study for consecutive subjects who underwent colonoscopy as a screening exam at the Center for Health Promotion, Samsung Medical Center, from March 2004 to December 2005. According to the modified ATP III criteria, metabolic syndrome was diagnosed. We classified a total of 2,531 subjects into the adenoma group (n = 731) and the control group (n = 1,800), including normal colonoscopic finding, nonpolyp benign lesions, or histologically confirmed hyperplastic polyp. RESULTS: The prevalence for metabolic syndrome was 17% in the adenoma group and 11% in the control group. On the multiple logistic regression analyses, metabolic syndrome was found to be associated with an increased risk of colorectal adenoma (odds ratio, 1.51; 95% confidence interval, 1.18-1.93). Also, waist circumference among the individual components of metabolic syndrome was an independent risk factor for colorectal adenoma. An increased risk for metabolic syndrome was more evident for proximal than distal colon, for multiple (>/=3), and for advanced adenoma in the adenoma group. CONCLUSION: Metabolic syndrome was associated with colorectal adenoma. Abdominal obesity of the individual components of metabolic syndrome was an important risk factor for colorectal adenoma.     

Thymidylate synthase polymorphisms, folate and B-vitamin intake, and risk of colorectal adenoma

The effects of polymorphisms in genes coding for key folate metabolism enzymes such as thymidylate synthetase (TS) on colorectal neoplasia risk are likely to be influenced by gene-gene and gene-nutrient interactions. We investigated the combined effects of three polymorphisms in the TS gene region, TSER, TS 3R G>C, and TS 1494del6, dietary intakes of folate and other B vitamins, and genotype for other folate metabolism variants, in a colorectal adenoma (CRA) case-control study. Individuals homozygous for TS 1494del6 del/del were at significantly reduced CRA risk compared to those with either ins/del or ins/ins genotypes (odds ratio 0.52; 95% confidence interval: 0.31-0.85, P=0.009). We also observed evidence of interactions between TS 1494del6 genotype and intake of folate, and vitamins B6 and B12, and MTHFR C677T genotype, with the reduction in risk in del/del homozygotes being largely confined to individuals with high nutrient intakes and MTHFR 677CC genotype (P interaction=0.01, 0.006, 0.03, and 0.07, respectively). TSER genotype, when considered either alone or in combination with TS 3R G>C genotype, did not significantly influence CRA risk. These findings support a role for TS in colorectal carcinogenesis, and provide further evidence that functional polymorphisms in folate metabolism genes act as low-risk alleles for colorectal neoplasia and participate in complex gene-gene and gene-nutrient interactions.     

Fumes from meat cooking and lung cancer risk in Chinese women.

Chinese women are recognized to have a high incidence of lung cancer despite a low smoking prevalence. Several studies have implicated domestic exposure to cooking fumes as a possible risk factor, although the exact carcinogens have yet to be identified. Heterocyclic amines are known carcinogens, which have been identified in cooked meat, and also in fumes generated during frying or grilling of meats. We conducted a case-control study of 303 Chinese women with pathologically confirmed, primary carcinomas of the lung and 765 controls to examine the association between exposure to meat cooking and lung cancer risk. Data on demographic background, smoking status, and domestic cooking exposure, including stir-frying of meat, were obtained by in-person interview while in hospital. The response rates among eligible cases and controls were 95.0 and 96.9%, respectively. The proportion of smokers (current or ex-smokers) among cases and controls was 41.7 and 13.1%, respectively. Adenocarcinomas comprised 31.5% of cancers among smokers and 71.6% among nonsmokers. When cases were compared with controls, the odds ratio (OR) for lung cancer (all subtypes) among ex-smokers was 4.3 [95% confidence interval (CI) 2.7-6.8] and that among current smokers was 5.0 (95% CI, 3.4-7.3). Among smokers, women who reported that they stir-fried daily in the past had a significantly increased risk of lung cancer (adjusted OR, 2.0; 95% CI, 1.0-3.8) and among these women, risk was enhanced for those who stir-fried meat daily (OR, 2.7; 95% CI, 1.3-5.5). Women who stir-fried daily but cooked meat less often than daily did not show an elevated risk (OR, 1.0. 95% CI, 0.5-2.4). Risk was further increased among women stir-frying meat daily who reported that their kitchen was filled with oily fumes during cooking (OR, 3.7; 95% CI, 1.8-7.5). These cooking practices on their own did not increase risk among nonsmokers in our study population. Our results suggest that inhalation of carcinogens, such as heterocyclic amines generated during frying of meat, may increase the risk of lung cancer among smokers. Further studies in different settings are warranted to examine this possibility, which may also help to explain the higher risk observed among women smokers compared with men.     

Associations between S-adenosylmethionine,S-adenosylhomocysteine,and colorectal adenoma risk are modified by sex

Methionine metabolism is an important component of one-carbon metabolism. S-adenosylmethionine (SAM), the methyl donor for nearly all methylation reactions, is irreversibly converted to S-adenosylhomocysteine (SAH), an inhibitor of methyltransferases, some of which are key enzymes for methylation. Changes in DNA methylation are common in colorectal cancers. We evaluated plasma SAM and SAH with colorectal adenoma risk in a matched case-control study conducted among individuals undergoing routine colonoscopy. 216 cases were individually matched to polyp-free controls in a 1:1 ratio on age (± 5 years), sex, race (white/non-white), study site (academic medical center/VA hospital) and date of sample collection (± 60 days). Sex-specific quantiles were evaluated based on the control distribution due to vastly different metabolite levels by sex. Conditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Among males, both higher SAM (OR = 0.38, 95% CI: 0.18-0.77, p for trend = 0.007) and higher SAH (OR = 0.45, 95% CI: 0.22-0.91, p for trend = 0.02) were associated with statistically significantly decreased risks of colorectal adenoma in comparison to lowest plasma SAM or SAH tertile. Conversely, among females, both higher SAM and higher SAH were associated with increased risk of colorectal adenoma, which was statistically significant for SAH (OR = 5.18, 95% CI: 1.09-24.62, p for trend = 0.04). The difference in these associations between men and women was statistically significant (p < 0.05). The ratio of SAM/SAH was not associated with colorectal adenoma risk among males or females. These findings suggest SAM and SAH may be involved in the development of colorectal adenoma and the association may be modified by sex.