Our follow-up study of 575 female NHL patients suggests that pre-diagnostic alcohol consumption might affect the prognosis and survival of NHL patients, and the impact varies by NHL subtype and type of alcohol consumed. Wine drinking appeared to favor NHL prognosis and survival, particularly for DLBCL, the most common NHL subtype. Light consumption of beer showed benefit for NHL overall while no effect was observed when different NHL subtypes were analyzed separately. Liquor drinking was associated with an increased risk of negative outcomes in DLBCL patients, such as relapse, occurrence of secondary cancer, and death. The findings warrant replication in other studies.
One of our main findings is that pre-diagnostic wine consumption was associated with a better survival among NHL patients; particularly, a reduced risk of death, relapse and secondary cancer occurrence was observed among DLBCL patients. Extensive laboratory studies have shown that the polyphenolic constituents rich in grapes, which are abundant in wine, such as flavonoids and resveratrol, could block carcinogenesis and inhibit the growth of tumors in animals or cell culture [23
]. These polyphenols have been well demonstrated to have anti-oxidative [24
] and anti-inflammatory [25
] effects; emerging evidence showed that they also exhibited additional biological properties and could interfere with multistage tumor onset and tumor growth, such as preventing DNA alteration by inhibition of phase I enzymes, induction of phase II enzymes, stimulation of DNA repair [27
], inhibiting cell proliferation by cell cycle arrest [28
], modulating growth-related signal transduction pathways through altering expression of protein kinases [32
], and activating apoptosis [28
]. Besides the anti-cancer effects, the polyphenols [39
] or moderate wine drinking [11
] has been shown inversely associated with the risk of cardiovascular diseases (CVD), the No. 1 killer in the U.S. and to which cancer survivors are especially prone [46
], which may also contribute to the better OS and DFS we observed among wine drinkers. The medical history of CVD was not collected at diagnosis or during the follow-up in our study. However, efforts were made by looking at cause of death. There were 11 deaths from CVD out of 224 non-wine drinkers (5%) compared with 10 deaths from CVD out of 260 wine-drinkers (4%).
Another possible explanation of our observation of wine’s favorable effect and liquor’s adverse effect on NHL patients’ prognosis and survival is that moderate wine drinking is associated with a higher socio-economic status and lifestyle leading to a healthier diet, while liquor drinking may indicate the opposite. In our population, wine drinkers had a higher average consumption of vegetables and fruit (3.86 vs. 3.74 medium servings per day) but a higher consumption of saturated fat (27.67 vs. 26.95 gm per day) than never drinkers, and liquor drinkers had a lower average consumption of vegetables and fruit (3.64 vs. 3.74 medium servings per day) and a higher consumption of saturated fat (28.28 vs. 26.95 gm per day) than never drinkers, but the differences were not statistically significant. Besides adjusting for clinical factors and education as a measure of socio-economic status, attempts were also made to control potential confounding by other nutritional factors such as total energy intake, intake of protein, fat, carbohydrates, vegetables and fruits, and body mass index, all of which did not result in material changes of the observed associations and thus were not included in the final models. However, we could not eliminate the possibility that the residual confounding may contribute to the observed associations.
Two studies conducted in Italy examined the relationship between alcohol consumption and survival in NHL patients [15
], and both found that drinkers had a poor survival and a higher risk of death than non-drinkers. By taking types of alcohol consumed into consideration, our study added information to the previous studies: our study shows that NHL survival varies by alcohol type and that the favorable effect was mainly seen in wine-drinkers and detrimental effects were mainly seen in liquor-drinkers. Unlike those two studies, we did not observe poor survival or higher risk of death among drinkers of alcohol overall; this discrepancy could be due to the different study populations. Compared to the Italian studies’ populations, our study population has a significant lower proportion of drinkers (61% vs. 79%) [15
] and lower levels of alcohol consumption (median intensity 0.5 vs. 4 drinks per day; median duration 30 vs. 40 years; median lifetime consumption 34.5 vs. 295 kg ethanol) [15
]. A U- or J-shape relationship has been well established between alcohol consumption and other health outcomes, and could exist for NHL survival as well. A possible explanation for the discrepancy is that the consumption level of our study population might lie before while the Italian studies were far beyond the bottom of the U- or J-shape curve. The discrepancy could also be due to gender differences: our study included only females, while the other studies included both genders—638 men and 495 women in one study [15
] and 154 men and 114 women in the other [16
]—neither of those studies stratified their analyses by gender.
One strength of our study is that the alcohol consumption was analyzed thoroughly. We analyzed not only whether drinking occurred or not, but also the initiation age, intensity, duration, and life time consumption, and types of drinking. Given that the biological mechanism of alcohol drinking on cancer survival is not clear, any of these indicators could be relevant to the outcome of NHL survival. This thorough analysis allowed us to evaluate each of the effects individually and separate the effects of different types of drinking. We also conducted factor analysis and found four resulting factors. Among them, roughly speaking, three correspond to beer, wine, and liquor drinking, respectively; and the other factor corresponds to intensity of ethanol intake. Using the four factors (as opposed to the original measurements) in the Cox models, we reached a similar conclusion: wine drinking was significantly associated with DLBCL survival.
The second strength of our study is the utilization of CTR to obtain follow-up information. According to the recently submitted SEER database (Nov 2007) [47
], among those microscopically confirmed female NHL patients diagnosed in 1996–2000 in CT and aged 21–84, 99.2% were actively followed by CTR through 12/31/2004. Through CTR, we obtained the information on tumor stage, B-symptoms and initial treatment; by adjusting them as confounders in our analysis, we were able to examine the independent effect of alcohol consumption on NHL prognosis and survival. Another strength of our study is the relatively large sample size, which provides power to detect differences among NHL subtypes, especially for the most common subtype DLBCL.
A limitation of our study is that patients were interviewed only at entrance in the study, and some subjects may have changed their drinking habits during follow-up. Therefore, our observation reveals only the association between pre-diagnostic alcohol consumption and NHL survival and cautions should be taken when explaining the relationship between post-diagnostic alcohol consumption and NHL survival. Another limitation lies in the possible incomplete information on relapse and secondary cancer occurrence abstracted from CTR, especially among patients who were no longer CT residents, which could cause our measure of DFS longer than the true. However, this information bias is unlikely to be associated with drinking habits, thus our observed associations on DFS may be biased towards the null due to this non-differential misclassification.
In conclusion, our study shows that pre-diagnostic wine drinking may favor NHL prognosis and survival, especially among DLBCL patients, while liquor might negatively affect DLBCL prognosis and survival. The analyses for different histological subtypes suggest that the effect of alcohol consumption on prognosis and survival might be different among NHL subtypes. Our findings should be confirmed by other studies.