Smoking and risk of colorectal cancer.

Tobacco smoking was studied in relation to colorectal cancer in 56 973 Finnish men and women initially free from cancer. Smoking status was determined by a health questionnaire. During a follow-up period of 28 years, from the baseline in 1966-72 to the end of 1994, 457 cases of colorectal cancer occurred. There was no significant association between baseline smoking status and colorectal cancer risk over the total follow-up period. The sex- and age-adjusted relative risk of colorectal cancer between smokers and non-smokers was 1.06 (95% confidence interval 0.84-1.33). For follow-up periods of 11-20 years, however, the relative risk was 1.57 (95% confidence interval 1.09-2.24). In a subgroup in which smoking habits were assessed twice, the relative risk of colorectal cancer among persistent smokers was 1.71 (95% confidence interval 1.09-2.68) compared with others. The results of the present prospective study are consistent with the possibility that smoking increases the risk of colorectal cancer after a relatively long induction period. To clarify the role of smoking in colorectal cancer development, further cohort studies are needed with long follow-up periods and allowing for control of dietary and other potential confounding factors.     

Multiple behavioral risk factors for colorectal cancer and colorectal cancer screening status.

BACKGROUND: Individuals who are not adherent to colorectal cancer screening have a greater prevalence of several other behavioral risk factors for colorectal cancer than adherent individuals. However, previous relevant studies have typically not considered the co-occurrence of such behavioral risk factors at the individual level. In the current study, we examined the prevalence, patterns, and predictors of multiple behavioral risk factors for colorectal cancer according to colorectal cancer screening status (adherent versus not adherent). METHODS: The study sample consisted of 11,090 individuals ages 50 years and older who participated in the 2000 National Health Interview Survey. Based on responses to survey questions, individuals were categorized as being adherent or not adherent to colorectal cancer screening guidelines and were also denoted as having or not having each of seven behavioral risk factors for colorectal cancer (smoking, low physical activity, low fruit and vegetable intake, high caloric intake from fat, obesity, high alcohol intake, and low intake of multivitamins). RESULTS: Individuals who were not adherent to screening reported having a greater number of risk factors than adherent individuals. For each screening group, there was a high prevalence of having low physical activity, low fruit and vegetable intake, and low intake of multivitamins. Demographic and health-related correlates of behavioral risk factor prevalence were identified in both screening groups. CONCLUSIONS: In combination with efforts to promote colorectal cancer screening uptake and adherence, there is a need to develop interventions to modify the colorectal cancer behavioral risk factors that are common among screening-adherent and nonadherent individuals.     

Meal frequency and risk of colorectal cancer.

The relation between meal frequency and the risk of colorectal cancer was investigated in a case-control study conducted in North Italy on 889 cases of colon cancer, 581 cases of rectal cancer, and 2475 controls admitted to hospital for acute, nonneoplastic, or digestive disorders. As compared to individuals who reported 2 or fewer meals per day, the multivariate colon cancer odds ratios were 1.7 [95% confidence interval (95% CI), 1.5-2.1] for 3, and 1.9 (95% CI, 1.1-3.3) for 4 meals or more. Corresponding rectal cancer odds ratios were 1.4 (95% CI, 1.1-1.7) for 3, and 1.9 (95% CI, 1.1-3.5) for 4 meals or more. The direct trends in risk of colorectal cancer with frequency of eating were not substantially modified by allowance for various dietary and nondietary potential confounding factors, including an approximate measure of total energy intake, and did not show significant effect modification across strata of age, sex, education, and other major risk covariates. A role of meal frequency in the etiology of colorectal cancer is biologically plausible, since when a meal is eaten, the gallbladder contracts and releases bile acids. Thus, eating patterns can influence the enterohepatic circulation and, consequently, the exposure time of intestinal mucosa to bile acids.     

Perceived risk of colorectal cancer: sources of risk judgments.

Perceived risk of disease plays a key role in health behaviors, making it an important issue for cancer-preventive behavior research. This study describes studies using complimentary methodologies to investigate the determinants of perceived risk of developing colorectal cancer. In study 1, questionnaires were mailed to a community sample of 1,056 adults ages 45 to 65 years. They assessed risk factors for colorectal cancer and perceived risk of colorectal cancer and asked respondents to explain why they had rated their risk as they had. Consistent with previous studies, risk factors for colorectal cancer were significantly correlated with perceived risk, although associations were relatively weak. The most frequently cited reasons for risk judgments were diet, family history, and symptoms/general health. Not surprisingly, correlations between each risk factor and perceived risk were stronger among participants who had attributed their risk to that factor. Study 2 used semi-structured interviews to explore individuals' explanations for their perceived risk of colorectal cancer. Adults (n = 18) ages 60 to 63 years volunteered a variety of explanations, but their experiences of cancer seemed to be most salient to their risk estimates. These studies suggest that attributions people make for their risk judgments are important in understanding how they conceptualize risk, but appreciation of experiential and affective influences may be useful in fully understanding perceptions of risk.     

Dietary flavonoids and the risk of colorectal cancer.

In vitro and in vivo laboratory data point to chemoprotective effects of flavonoids on colorectal cancer. However, there has been limited epidemiologic research on the dietary intake of flavonoids and risk of colorectal cancer. Recent expansions of dietary databases to include flavonoid data now make such studies feasible. Association between the six main classes of flavonoids and the risk of colorectal cancer was examined using data from a national prospective case-control study in Scotland, including 1,456 incident cases and 1,456 population-based controls matched on age, sex, and residence area. Dietary, including flavonoid data, were obtained from a validated, self-administered food frequency questionnaire. Risk of colorectal cancer was estimated using conditional logistic regression models in the whole sample and stratified by sex, smoking status, and cancer site and adjusted for established and putative risk factors. After energy adjustment, reductions in colorectal cancer risk associated with the highest quartiles of intake (versus the lowest quartile) were 27% for flavonols [odds ratio (OR), 0.73; P(trend) = 0.012], 32% for quercetin (OR, 0.68; P(trend) = 0.001), 32% for catechin (OR, 0.68; P(trend) < 0.0005); 26% for epicatechin (OR, 0.74; P(trend) = 0.019), and 22% for procyanidins (OR, 0.78; P(trend) = 0.031). The significant dose-dependent reductions in colorectal cancer risk that were associated with increased consumption of flavonols, quercetin, catechin, and epicatechin remained robust after controlling for overall fruit and vegetable consumption or for other flavonoid intake. The risk reductions were greater among nonsmokers, but no interaction beyond a multiplicative effect was present. Sex-specific or cancer-type differences were not observed. No risk reductions were associated with intake of flavones (P(trend) = 0.64), flavonones (P(trend) = 0.22), and phytoestrogens (P(trend) = 0.26). This was the first of several a priori hypotheses to be tested in this large study and showed strong and linear inverse associations of flavonoids with colorectal cancer risk.     

Family history of cancer and risk of colorectal cancer in Italy.

Subjects with a family history of colorectal cancer (CRC) are at increased risk of CRC, but quantification of the risk in different populations, the possible differences in risk according to localization of the cancer and the association of family history of other cancers with CRC risk are still open issues. We have therefore analysed data from a multicentric case-control study conducted in six Italian areas between 1992 and 1996 of 1225 incident cases of colon cancer, 728 cases of rectal cancer and 4154 controls admitted for acute conditions to the same network of hospitals as the cases. Unconditional logistic regression models including terms for gender, age, study centre, years of education and number of siblings were used to estimate the odds ratios (ORs) of CRC according to various aspects of history of CRC and other cancers in first-degree relatives. The OR for family history of CRC was 3.2 (95% confidence interval, CI, 2.5-4.1) for colon cancer and 2.2 (95% CI 1.6-3.1) for rectal cancer. Colon cancer was significantly associated with a family history of stomach (OR 1.4), bone (OR 2.1) and kidney (OR 2.3) cancers, while rectal cancer was significantly associated with a family history of lymphomas (OR 2.8). There was a 30% higher risk of colon and rectal cancer in subjects with a family history of any cancer, excluding intestine. The ORs for family history of CRC were 5.2 for colon and 6.3 for rectum when the proband''s age was below 45 years. The ORs were similar when the affected relative was a parent or a sibling and in different strata of age of relative(s). For subjects with two or more first-degree relatives with CRC, the risk was 6.9 for the right colon, 5.8 for the transverse and descending colon, 3.8 for the sigma, 3.2 for the rectosigmoid junction and 1.9 for the rectum. This study confirms that a family history of CRC in first-degree relatives increases the risk of both colon and rectal cancer, the association being stronger at younger ages and for right colon.     

Death receptor 4 variants and colorectal cancer risk.

The tumor necrosis factor-related apoptosis-inducing ligand receptor modulates apoptotic response by binding to the proapoptotic death receptor 4 (DR4). Perturbed apoptosis due to missense alterations in the candidate tumor suppressor gene DR4 leads to deregulated cell proliferation and cancer predisposition. Recent studies have discussed the association of DR4 variants with cancer risk. We evaluated, for the first time, the role of the Thr(209)Arg (626C>G) and Glu(228)Ala (683A>C) polymorphisms on colorectal cancer risk by genotyping 659 incident cases and 607 healthy controls drawn from the German population-based Darmkrebs: Chancen der Verhütung durch Screening (DACHS) study. Whereas DR4 Glu(228)Ala was not associated with colorectal cancer, Thr(209)Arg heterozygotes were at a significantly decreased colorectal cancer risk [odds ratio (OR), 0.73; 95% confidence interval (95% CI), 0.54-0.97]. Stratification according to sex and age exhibited a significant association of Thr(209)Arg with a decreased risk for male heterozygotes (OR, 0.68; 95% CI, 0.46-0.99) and for Arg(209) carriers > or =65 years of age (OR, 0.65; 95% CI, 0.46-0.92) as well as an enhanced risk for female Ala(228) carriers in a allele dose-dependent manner (P(trend) = 0.01). Subsite analysis revealed a protective effect of Thr(209)Arg for rectal cancer risk (OR, 0.67; 95% CI, 0.48-0.95) and a significant risk increase for Ala(228) carriers with advanced colorectal cancer stages (P(trend) = 0.04). Haplotype analysis revealed a 2.4-fold risk for carriers of the rare 626C-683C haplotype (1% prevalence in the general population; OR, 2.37; 95% CI, 0.98-5.76). The score statistic yielded an empirical P of 0.03 of the haplotype-specific test for 626C-683C based on 20,000 simulations, suggesting that DR4 626C-683C may affect colorectal cancer predisposition.     

Insulin-like growth factor polymorphisms and colorectal cancer risk.

Several modifiable lifestyle factors, such as physical activity, obesity, and postmenopausal hormone use, have been associated with colorectal cancer risk. It has been hypothesized that some or all of these factors may mediate their effects through alterations in insulin-like growth factor-1 (IGF-1) and its binding proteins (IGFBP). To evaluate the role of IGFs in colorectal cancer, we examined the relationship of two common genetic polymorphisms in IGF-1 (a cytosine-adenosine dinucleotide repeat) and IGFBP-3 (a G --> C single nucleotide polymorphism) with colorectal cancer risk, as well as their potential modification by physical activity, body mass index (BMI), and postmenopausal hormone use. Subjects included 782 male and female colorectal cancer cases diagnosed between 1998 and 2002 and reported to the statewide registry in the metropolitan Seattle area, and 503 age- and sex-matched cancer-free population controls. Colorectal cancer was modestly associated with having an IGF-1 genotype other than homozygous for 19 repeats (odds ratio, 1.3; 95% confidence interval, 1.0-1.6) and having the GG IGFBP-3 genotype (odds ratio, 1.3; 95% confidence interval, 1.0-1.8). There was evidence that IGF-1 genotype modified the relationship between BMI and colorectal cancer among women, such that high BMI increased risk of colorectal cancer only among those with the 19/19 genotype (P(interaction) = 0.02). IGFBP-3 genotype was also a significant effect modifier of the relationship between risk factors and colorectal cancer: The positive association between BMI and colorectal cancer was observed only among men (P(interaction) < 0.01) and women (P(interaction) = 0.06) with the GG genotype; the inverse association between postmenopausal hormone use and colorectal cancer was observed only among women with the GG genotype (P = 0.01) and the inverse association between physical activity and colorectal cancer was observed only among men who carried the C allele (P < 0.01). The current study provides some support for a role of IGFs in colorectal cancer etiology, particularly in mediating the relationship of common risk factors (physical activity, BMI, and postmenopausal hormone use).     

Meta-analyses of colorectal cancer risk factors

Purpose

Demographic, behavioral, and environmental factors have been associated with increased risk of colorectal cancer (CRC). We reviewed the published evidence and explored associations between risk factors and CRC incidence.

Methods

We identified 12 established non-screening CRC risk factors and performed a comprehensive review and meta-analyses to quantify each factor’s impact on CRC risk. We used random-effects models of the logarithms of risks across studies: inverse-variance weighted averages for dichotomous factors and generalized least squares for dose–response for multi-level factors.

Results

Significant risk factors include inflammatory bowel disease (RR = 2.93, 95 % CI 1.79–4.81); CRC history in first-degree relative (RR = 1.80, 95 % CI 1.61–2.02); body mass index (BMI) to overall population (RR = 1.10 per 8 kg/m² increase, 95 % CI 1.08–1.12); physical activity (RR = 0.88, 95 % CI 0.86–0.91 for 2 standard deviations increased physical activity score); cigarette smoking (RR = 1.06, 95 % CI 1.03–1.08 for 5 pack-years); and consumption of red meat (RR = 1.13, 95 % CI 1.09–1.16 for 5 servings/week), fruit (RR = 0.85, 95 % CI 0.75–0.96 for 3 servings/day), and vegetables (RR = 0.86, 95 % CI 0.78–0.94 for 5 servings/day).

Conclusions

We developed a comprehensive risk modeling strategy that incorporates multiple effects to predict an individual’s risk of developing CRC. Inflammatory bowel disease and history of CRC in first-degree relatives are associated with much higher risk of CRC. Increased BMI, red meat intake, cigarette smoking, low physical activity, low vegetable consumption, and low fruit consumption were associated with moderately increased risk of CRC.     

Selected micronutrient intake and the risk of colorectal cancer.

The relationship between estimated intake of selected micronutrients and the risk of colorectal cancer was analysed using data from a case-control study conducted in northern Italy. The study was based on 828 patients with colon cancer, 498 with rectal cancer and 2,024 controls in hospital for acute, non-neoplastic, non-digestive tract diseases. Relative risks (RRs) of intake quintiles were computed after allowance for age, sex and other major potential confounding factors, including an estimate of total energy intake. No apparent trend in risk across intake quintiles was evident for retinol, vitamin D, methionine and calcium. For beta-carotene, ascorbic acid, vitamin E and folate there was a trend of a protective effect with increasing consumption: the RR for the highest versus the lowest quintile was 0.32 for beta-carotene, 0.40 for ascorbic acid, 0.60 for vitamin E and 0.52 for folate. These inverse associations were similar for colon and rectal cancer, and consistent across strata of sex and age. When simultaneous allowance was made for all these micronutrients, besides other covariates, the only persistent protective effects were for beta-carotene (RR = 0.38 for the highest quintile) and ascorbic acid (RR = 0.52). Whether this reflects a specific, or stronger, effect of these micronutrients, rather than problems of collinearity between micronutrients or other limitations of the data, remains open to discussion. Still, this study suggests that specific micronutrients may exert an independent protective effect against colorectal carcinogenesis.     

Self-reported birth weight and subsequent risk of colorectal cancer.

Case series data suggest that high birth weight and neonatal macrosomia in offspring are associated with an increased risk of colorectal cancer in parents. We therefore conducted a prospective analysis investigating the association among self-reported birth weight, neonatal macrosomia, and incident colorectal cancer in a population-based study of men and women. Participants were drawn from a cohort of men and women ages between 45 and 79 years: the European Prospective Investigation of Cancer in Norfolk study. A total of 4532 men and 7325 women who reported their birth weight were followed up between 1993 and 1999. The relation between birth weight and incident colorectal cancer was assessed using Cox's proportional hazards model. All Ps are two-sided. The association between self-reported birth weight and risk of incident colorectal cancer was nonlinear. Relative to individuals born weighing 2500-3249 g, the adjusted hazard ratio for people born with neonatal macrosomia was 2.57 (95% confidence interval = 1.15-5.74). There was also some evidence that low birth weight babies were at increased risk of colorectal cancer relative to the referent category. These risks were essentially unaltered after adjustment for potential confounders. There is a J-shape relation between self-reported birth weight and subsequent risk of colorectal cancer. Babies born with macrosomia appear to have the greatest risk.     

PTPRJ haplotypes and colorectal cancer risk

Recent studies from mouse mapping studies for cancer susceptibility have successfully led to the identification of a handful of susceptibility genes. Ptprj was identified as a strong candidate gene for mouse locus susceptibility to colorectal cancer 1, and one variant, rs1566734, showed evidence of preferential allelic imbalance in human colorectal tumors. Haplotypes in human PTPRJ have also been associated with protective effects for breast cancer risk. To determine if variants or haplotype in PTPRJ confer protective or risk effects for colorectal cancer (CRC), we genotyped rs1566734 and six additional PTPRJ haplotype tagging single nucleotide polymorphisms (SNP) in CRC cases and controls from the Molecular Epidemiology of Colorectal Cancer study. There was no evidence for cancer risk with rs1566734 in 1,897 cases and 1,954 controls with a homozygote odds ratio of 1.09 and 95% confidence interval of 0.85 to 1.39. The 6 tagging SNPs resulted in 6 main haplotypes (frequencies, >1%). None of the six tagSNPs individually showed significant evidence for risk; however, rs1503185 showed a nonsignificant protective effect. One haplotype was overrepresented in cases compared with controls, corresponding to a 34% increase in risk CRC, but there was no significant difference overall in haplotype frequencies between cases and controls (global test P statistic=0.19). From this study, we observe no significant increase in risk for human CRC with variants or haplotypes in PTPRJ. Additional studies are warranted to study possible PTPRJ-interacting loci, which are observed with Scc1 in the mouse models for CRC susceptibility.     

Food groups and colorectal cancer risk

Most studies of diet and colorectal cancer have considered nutrients and micronutrients, but the role of foods or food groups remains open to debate. To elucidate the issue, we examined data from a case-control study conducted between 1992 and 1997 in the Swiss canton of Vaud. Cases were 223 patients (142 men, 81 women) with incident, histologically confirmed colon (n= 119) or rectal (n= 104) cancer (median age 63 years), linked with the Cancer Registry of the Swiss Canton of Vaud, and controls were 491 subjects (211 men, 280 women, median age 58 years) admitted to the same university hospital for a wide spectrum of acute non-neoplastic conditions unrelated to long-term modifications of diet. Odds ratios (OR) were obtained after allowance for age, sex, education, smoking, alcohol, body mass index, physical activity and total energy intake. Significant associations were observed for refined grain (OR = 1.32 for an increase of one serving per day), and red meat (OR = 1.54), pork and processed meat (OR = 1.27), alcohol (OR = 1.28), and significant protections for whole grain (OR = 0.85), raw (OR = 0.85) and cooked vegetables (OR = 0.69), citrus (OR = 0.86) and other fruits (OR = 0.85), and for coffee (OR = 0.73). Garlic was also protective (OR = 0.32 for the highest tertile of intake). These findings in a central European population support the hypothesis that a diet rich in refined grains and red meat increases the risk of colorectal cancer; they, therefore, support the recommendation to substitute whole grains for refined grain, to limit meat intake, and to increase fruit and vegetable consumption.     

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.     

Eating frequency and risk of colorectal cancer

Purpose

Eating frequency is a modifiable aspect of dietary behavior that may affect risk of colorectal cancer (CRC). Although most previous case–control studies indicate a positive association, two prospective studies suggest an inverse association between eating frequency and CRC risk, with evidence of effect modification by diet composition. We examined the association between eating frequency and CRC in a large, prospective cohort study, and explored whether this relationship was modified by sex, coffee consumption, or dietary glycemic load.

Methods

Between 2000 and 2002, 67,912 western Washington residents aged 50–76 reported average daily meal and snack frequency using a mailed questionnaire as part of the vitamins and lifestyle study. Participants were followed for CRC through linkage with SEER through 2008, over which time 409 CRC cases developed. Hazard Ratios and 95 % Confidence Intervals were obtained using Cox regression.

Results

In age- and sex-adjusted models higher (5+ times/d) vs. lower (1–2 times/d) eating frequency was associated with a HR of 0.62 (95 % CI 0.43?0.88, P_trend = 0.001). However, following further adjustment for BMI, race/ethnicity, alcohol, and other known CRC risk factors, the relationship was no longer statistically significant (HR: 0.76; 95 % CI 0.51, 1.14). No effect modification was observed by sex (P_interaction = 0.45), coffee consumption (P_interaction = 0.44), or dietary glycemic load (P_interaction = 0.90). In subgroup analyses by tumor site, higher vs. lower eating frequency was associated with lower risk for colon (HR 0.65 95 % CI 0.39–1.07, P_trend = 0.04), but not rectal cancers (HR = 1.08 95 % CI 0.54–2.18, P_trend = 0.94).

Conclusion

The weak inverse association observed between eating frequency and CRC is consistent with findings from other prospective studies. Modification of this relationship by diet quality and participant characteristics should be considered in the future studies.     

Food groups and risk of colorectal cancer

The aim of this systematic review and meta‐analysis was to summarize the evidence on the relationship between intake of 12 major food groups, including whole grains, refined grains, vegetables, fruit, nuts, legumes, eggs, dairy, fish, red meat, processed meat and sugar‐sweetened beverages with risk of colorectal cancer (CRC). We conducted a systematic search in PubMed and Embase for prospective studies investigating the association between these 12 food groups and risk of CRC until April 2017. Summary risk ratios (RRs) and 95% confidence intervals (95% CI) were estimated using a random effects model for high vs. low intake categories, as well as for linear and nonlinear relationships. An inverse association was observed for whole grains (RR_30g/d: 0.95, 95% CI 0.93, 0.97; n = 9 studies), vegetables (RR_100g/d: 0.97, 95% CI 0.96, 0.98; n = 15), fruit (RR_100g/d: 0.97, 95% CI 0.95, 0.99; n = 16) and dairy (RR_200g/d: 0.93, 95% CI 0.91, 0.94; n = 15), while a positive association for red meat (RR_100g/d: 1.12, 95% CI 1.06, 1.19; n = 21) and processed meat (RR_50g/d: 1.17, 95% CI 1.10, 1.23; n = 16), was seen in the linear dose‐response meta‐analysis. Some evidence for nonlinear relationships was observed between vegetables, fruit and dairy and risk of colorectal cancer. Findings of this meta‐analysis showed that a diet characterized by high intake of whole grains, vegetables, fruit and dairy products and low amounts of red meat and processed meat was associated with lower risk of CRC.     

Adiponectin gene and risk of colorectal cancer

Background:

Genes of the adiponectin pathway are interesting candidates for colorectal cancer risk based on the potential association between colorectal cancer and obesity. However, variants of the adiponectin gene (ADIPOQ) have been demonstrated to be inconsistently associated with risk of colorectal cancer.

Methods:

The current study attempted to evaluate these findings by examining several single nucleotide polymorphisms (SNPs) that were previously genotyped as part of a genome-wide association study in the ADIPOQ gene. Genotyping was also performed for a previously reported risk variant, rs266729, in 1062 individuals with a diagnosis of colorectal cancer and 1062 controls matched on age, gender and ethnicity (Jewish or not Jewish) as part of a population-based case–control study in Israel.

Results:

No evidence was found for an association between ADIPOQ and risk of colorectal cancer. The single nucleotide variant previously associated with decreased risk of colorectal cancer, rs266729, revealed an adjusted odds ratio of 1.04; 95% confidence interval, 0.88–1.23.

Conclusion:

The SNP, rs266729, was not strongly associated with colorectal cancer in patients of Ashkenazi Jewish descent or other ethnic groups in Israel.     

Family history and the risk of stomach and colorectal cancer.

BACKGROUND. The role of a family history of selected neoplasms in first-degree relatives in the risk of gastrointestinal cancers has been investigated, but requires further quantification. METHODS. A case-control study was conducted in northern Italy on 628 histologically confirmed incident cases of stomach cancer, 766 cases of colon cancer, 456 cases of rectal cancer, and 1766 controls admitted to hospital for acute, nonneoplastic, non-digestive tract disorders. RESULTS. Significant associations were observed between a family history of gastric cancer and stomach cancer risk (relative risk [RR], 2.6), and between a family history of intestinal cancer and colon (RR, 2.4) and rectal cancer (RR, 1.7). There was a tendency for the risks to be above unity for a family history of stomach cancer and for a number of other cancer sites (including esophagus, intestines, liver, pancreas, gallbladder, and lung), and the RR were of borderline statistical significance for cancer of the liver and intestines. The RR for a family history of lung cancer was 1.5 for stomach, 1.2 for colon, and 1.3 for rectal cancer, with none of the estimates being significant. There was no consistent pattern of risk with reference to the type of first-degree relationship; the RR was similar for stomach cancer with reference to parents and siblings, and for colon and rectal cancer, it was only moderately higher with reference to siblings. Significant trends in risk with the number of first-degree relatives were observed for all three cancer sites investigated. CONCLUSIONS. In terms of population attributable risk, approximately 8% of stomach cancers and 3% of colorectal cancers would be related to this familial component.